Abstract
Reproductive biology is a uniquely important topic since it is about germ cells, which are central for transmitting genetic information from generation to generation. In this review, we discuss recent advances in mammalian germ cell development, including preimplantation development, fetal germ cell development and postnatal development of oocytes and sperm. We also discuss the etiologies of female and male infertility and describe the emerging technologies for studying reproductive biology such as gene editing and single-cell technologies.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Abbott, D.H., Barnett, D.K., Bruns, C.M., and Dumesic, D.A. (2005). Androgen excess fetal programming of female reproduction: a developmental aetiology for polycystic ovary syndrome? Hum Reprod Update 11, 357–374.
Abbott, D.H., Dumesic, D.A., Eisner, J.R., Colman, R.J., and Kemnitz, J.W. (1998). Insights into the development of polycystic ovary syndrome (PCOS) from studies of prenatally androgenized female rhesus monkeys. Trends Endocrinol Metab 9, 62–67.
Abbott, D.H., Dumesic, D.A., and Franks, S. (2002). Developmental origin of polycystic ovary syndrome—a hypothesis. J Endocrinol 174, 1–5.
Abbott, D.H., Tarantal, A.F., and Dumesic, D.A. (2009). Fetal, infant, adolescent and adult phenotypes of polycystic ovary syndrome in prenatally androgenized female rhesus monkeys. Am J Primatol 71, 776–784.
Abudayyeh, O.O., Gootenberg, J.S., Essletzbichler, P., Han, S., Joung, J., Belanto, J.J., Verdine, V., Cox, D.B.T., Kellner, M.J., Regev, A., et al. (2017). RNA targeting with CRISPR-Cas13. Nature 550, 280–284.
Abudayyeh, O.O., Gootenberg, J.S., Konermann, S., Joung, J., Slaymaker, I.M., Cox, D.B.T., Shmakov, S., Makarova, K.S., Semenova, E., Minakhin, L., et al. (2016). C2c2 is a single-component programmable RNA-guided RNA-targeting CRISPR effector. Science 353, aaf5573.
Agarwal, A., Mulgund, A., Hamada, A., and Chyatte, M.R. (2015). A unique view on male infertility around the globe. Reprod Biol Endocrinol 13, 37.
Akin, L., Kendirci, M., Narin, F., Kurtoglu, S., Saraymen, R., Kondolot, M., Koçak, S., and Elmali, F. (2015). The endocrine disruptor bisphenol A may play a role in the aetiopathogenesis of polycystic ovary syndrome in adolescent girls. Acta Paediatr 104, e171–e177.
Al-Fozan, H. (2003). Left lateral predisposition of endometriosis and endometrioma. Obstet Gynecol 101, 164–166.
Anderson, A.D., Solorzano, C.M.B., and McCartney, C.R. (2014). Childhood obesity and its impact on the development of adolescent PCOS. Semin Reprod Med 32, 202–213.
Anderson, K.R., Haeussler, M., Watanabe, C., Janakiraman, V., Lund, J., Modrusan, Z., Stinson, J., Bei, Q., Buechler, A., Yu, C., et al. (2018). CRISPR off-target analysis in genetically engineered rats and mice. Nat Methods 15, 512–514.
Angka, L., Khan, S.T., Kilgour, M.K., Xu, R., Kennedy, M.A., and Auer, R. C. (2017). Dysfunctional natural killer cells in the aftermath of cancer surgery. Int J Mol Sci 18, 1787.
Antoniani, C., Romano, O., and Miccio, A. (2017). Concise review: epigenetic regulation of hematopoiesis: biological insights and therapeutic applications. Stem Cell Transl Med 6, 2106–2114.
Arafat, M., Har-Vardi, I., Harlev, A., Levitas, E., Zeadna, A., Abofoul-Azab, M., Dyomin, V., Sheffield, V.C., Lunenfeld, E., Huleihel, M., et al. (2017). Mutation in TDRD9 causes non-obstructive azoospermia in infertile men. J Med Genet 54, 633–639.
Arancio, W., Calogero Amato, M., Magliozzo, M., Pizzolanti, G., Vesco, R., and Giordano, C. (2018). Serum miRNAs in women affected by hyperandrogenic polycystic ovary syndrome: the potential role of miR-155 as a biomarker for monitoring the estroprogestinic treatment. Gynecol Endocrinol 34, 704–708.
Asghari, S., Valizadeh, A., Aghebati-Maleki, L., Nouri, M., and Yousefi, M. (2018). Endometriosis: perspective, lights, and shadows of etiology. Biomed Pharmaco Ther 106, 163–174.
Aston, K.I., and Carrell, D.T. (2009). Genome-wide study of single-nucleotide polymorphisms associated with azoospermia and severe oligozoospermia. J Androl 30, 711–725.
Aston, K.I., Krausz, C., Laface, I., Ruiz-Castané, E., and Carrell, D.T. (2010). Evaluation of 172 candidate polymorphisms for association with oligozoospermia or azoospermia in a large cohort of men of European descent. Hum Reprod 25, 1383–1397.
Austin, C.P., and Dawkins, H.J.S. (2017). Next decade’s goals for rare diseases. Nature 548, 158.
Avenarius, M.R., Hildebrand, M.S., Zhang, Y., Meyer, N.C., Smith, L.L.H., Kahrizi, K., Najmabadi, H., and Smith, R.J.H. (2009). Human male infertility caused by mutations in the CATSPER1 channel protein. Am J Hum Genet 84, 505–510.
Ayhan, Ö., Balkan, M., Guven, A., Hazan, R., Atar, M., Tok, A., and Tolun, A.ı. (2014). Truncating mutations in TAF4B and ZMYND15 causing recessive azoospermia. J Med Genet 51, 239–244.
Bae, S., Park, J., and Kim, J.S. (2014). Cas-OFFinder: a fast and versatile algorithm that searches for potential off-target sites of Cas9 RNA-guided endonucleases. Bioinformatics 30, 1473–1475.
Baldelli, R., Dieguez, C., and Casanueva, F.F. (2002). The role of leptin in reproduction: experimental and clinical aspects. Ann Med 34, 5–18.
Bannikov, A.V., and Lavrov, A.V. (2017). CRISPR/CAS9, the king of genome editing tools. Mol Biol (Mosk) 51, 582–594.
Barker, D.J. (1990). The fetal and infant origins of adult disease. BMJ 301, 1111.
Barr, S., Hart, K., Reeves, S., Sharp, K., and Jeanes, Y.M. (2011). Habitual dietary intake, eating pattern and physical activity of women with polycystic ovary syndrome. Eur J Clin Nutr 65, 1126–1132.
Bashamboo, A., Ferraz-de-Souza, B., Lourenço, D., Lin, L., Sebire, N.J., Montjean, D., Bignon-Topalovic, J., Mandelbaum, J., Siffroi, J.P., Christin-Maitre, S., et al. (2010). Human male infertility associated with mutations in NR5A1 encoding steroidogenic factor 1. Am J Hum Genet 87, 505–512.
Bay, K., and Anand-Ivell, R. (2014). Human Testicular Insulin-Like Factor 3 and Endocrine Disrupters. Endocrine Disrupt 94, 327–348.
Beall, S., Brenner, C., and Segars, J. (2010). Oocyte maturation failure: a syndrome of bad eggs. Fertil Steril 94, 2507–2513.
Benson, S., Janssen, O.E., Hahn, S., Tan, S., Dietz, T., Mann, K., Pleger, K., Schedlowski, M., Arck, P.C., and Elsenbruch, S. (2008). Obesity, depression, and chronic low-grade inflammation in women with polycystic ovary syndrome. Brain Behav Immun 22, 177–184.
Bibikova, M., Carroll, D., Segal, D.J., Trautman, J.K., Smith, J., Kim, Y.G., and Chandrasegaran, S. (2001). Stimulation of homologous recombination through targeted cleavage by chimeric nucleases. Mol Cell Biol 21, 289–297.
Bourc’his, D., and Bestor, T.H. (2006). Origins of extreme sexual dimorphism in genomic imprinting. Cytogenet Genome Res 113, 36–40.
Bourc’his, D., Xu, G.L., Lin, C.S., Bollman, B., and Bestor, T.H. (2001). Dnmt3L and the establishment of maternal genomic imprints. Science 294, 2536–2539.
Burney, R.O., and Giudice, L.C. (2012). Pathogenesis and pathophysiology of endometriosis. Fertil Steril 98, 511–519.
Byskov, A.G. (1986). Differentiation of mammalian embryonic gonad. Physiol Rev 66, 71–117.
Cai, H., Liu, B., Yang, T., Yang, Y., Xu, J., Wei, Z., Deng, G., Ning, G., Li, J., Wen, J., et al. (2018). Involvement of PKCε in FSH-induced connexin43 phosphorylation and oocyte maturation in mouse. Biol Open 7, bio034678.
Callaway, E. (2016). Gene-editing research in human embryos gains momentum. Nature 532, 289–290.
Capecchi, M.R. (1989). Altering the genome by homologous recombination. Science 244, 1288–1292.
Carone, B.R., Hung, J.H., Hainer, S.J., Chou, M.T., Carone, D.M., Weng, Z., Fazzio, T.G., and Rando, O.J. (2014). High-resolution mapping of chromatin packaging in mouse embryonic stem cells and sperm. Dev Cell 30, 11–22.
Carroll, D. (2011). Genome engineering with zinc-finger nucleases. Genetics 188, 773–782.
Chamindrani Mendis-Handagama, S.M.L., and Siril Ariyaratne, H.B. (2001). Differentiation of the adult Leydig cell population in the postnatal testis. Biol Reprod 65, 660–671.
Chandrasegaran, S., and Carroll, D. (2016). Origins of programmable nucleases for genome engineering. J Mol Biol 428, 963–989.
Chang, H.H.Y., Pannunzio, N.R., Adachi, N., and Lieber, M.R. (2017). Non-homologous DNA end joining and alternative pathways to double-strand break repair. Nat Rev Mol Cell Biol 18, 495–506.
Che, Q., Liu, M., Xu, J., Liu, Y., Cao, X., Dong, X., and Liu, S. (2019). Characterization of circular RNA expression profiles in cumulus cells from patients with polycystic ovary syndrome. Fertil Steril 111, 1243–1251.e1.
Chen, B., Li, B., Li, D., Yan, Z., Mao, X., Xu, Y., Mu, J., Li, Q., Jin, L., He, L., et al. (2017a). Novel mutations and structural deletions in TUBB8: expanding mutational and phenotypic spectrum of patients with arrest in oocyte maturation, fertilization or early embryonic development. Hum Reprod 32, 457–464.
Chen, B., Xu, P., Wang, J., and Zhang, C. (2019). The role of miRNA in polycystic ovary syndrome (PCOS). Gene 706, 91–96.
Chen, B., Zhang, Z., Sun, X., Kuang, Y., Mao, X., Wang, X., Yan, Z., Li, B., Xu, Y., Yu, M., et al. (2017b). Biallelic mutations in PATL2 cause female infertility characterized by oocyte maturation arrest. Am J Hum Genet 101, 609–615.
Chen, K.H., Boettiger, A.N., Moffitt, J.R., Wang, S., and Zhuang, X. (2015). Spatially resolved, highly multiplexed RNA profiling in single cells. Science 348, aaa6090.
Chen, Z.J., Zhao, H., He, L., Shi, Y., Qin, Y., Shi, Y., Li, Z., You, L., Zhao, J., Liu, J., et al. (2011). Genome-wide association study identifies susceptibility loci for polycystic ovary syndrome on chromosome 2p16.3, 2p21 and 9q33.3. Nat Genet 43, 55–59.
Cho, M.K., Kim, C.H., and Oh, S.T. (2009). Endometriosis in a patient with Rokitansky-Kuster-Hauser syndrome. J Obstet Gynaecol Res 35, 994–996.
Cho, S.W., Kim, S., Kim, J.M., and Kim, J.S. (2013). Targeted genome engineering in human cells with the Cas9 RNA-guided endonuclease. Nat Biotechnol 31, 230–232.
Cho, S.W., Kim, S., Kim, Y., Kweon, J., Kim, H.S., Bae, S., and Kim, J.S. (2014). Analysis of off-target effects of CRISPR/Cas-derived RNA-guided endonucleases and nickases. Genome Res 24, 132–141.
Choi, J.W., Zhou, W., Nie, Z.W., Niu, Y.J., Shin, K.T., and Cui, X.S. (2019). Spindlin1 alters the metaphase to anaphase transition in meiosis I through regulation of BUB3 expression in porcine oocytes. J Cell Physiol 234, 8963–8974.
Choi, Y., Jeon, S., Choi, M., Lee, M., Park, M., Lee, D.R., Jun, K.Y., Kwon, Y., Lee, O.H., Song, S.H., et al. (2010). Mutations in SOHLH1 gene associate with nonobstructive azoospermia. Hum Mutat 31, 788–793.
Chuang, P.C., Wu, M.H., Shoji, Y., and Tsai, S.J. (2009). Downregulation of CD36 results in reduced phagocytic ability of peritoneal macrophages of women with endometriosis. J Pathol 219, 232–241.
Ci, W., and Liu, J. (2015). Programming and inheritance of parental DNA methylomes in vertebrates. Physiology 30, 63–68.
Clarke, H.J., and Vieux, K.F. (2015). Epigenetic inheritance through the female germ-line: The known, the unknown, and the possible. Semin Cell Dev Biol 43, 106–116.
Cocuzza, M., Alvarenga, C., and Pagani, R. (2013). The epidemiology and etiology of azoospermia. Clinics 68, 15–26.
Coffey, S., and Mason, H. (2003). The effect of polycystic ovary syndrome on health-related quality of life. Gynecol Endocrinol 17, 379–386.
Colombo, R., Pontoglio, A., and Bini, M. (2017). Two novel TEX15 mutations in a family with nonobstructive azoospermia. Gynecol Obstet Invest 82, 283–286.
Cong, L., Ran, F.A., Cox, D., Lin, S., Barretto, R., Habib, N., Hsu, P.D., Wu, X., Jiang, W., Marraffini, L.A., et al. (2013). Multiplex genome engineering using CRISPR/Cas systems. Science 339, 819–823.
Cooper, H.E., Spellacy, W.N., Prem, K.A., and Cohen, W.D. (1968). Hereditary factors in the Stein-Leventhal syndrome. Am J Obstet Gynecol 100, 371–387.
Cooper, M.L., Choi, J., Staser, K., Ritchey, J.K., Devenport, J.M., Eckardt, K., Rettig, M.P., Wang, B., Eissenberg, L.G., Ghobadi, A., et al. (2018). An “off-the-shelf” fratricide-resistant CAR-T for the treatment of T cell hematologic malignancies. Leukemia 32, 1970–1983.
Cornu, T.I., Mussolino, C., and Cathomen, T. (2017). Refining strategies to translate genome editing to the clinic. Nat Med 23, 415–423.
Coutinho, L.M., Ferreira, M.C., Rocha, A., Carneiro, M.M., and Reis, F.M. (2019). New biomarkers in endometriosis. Adv Clin Chem 89, 59–77.
Coutton, C., Martinez, G., Kherraf, Z.E., Amiri-Yekta, A., Boguenet, M., Saut, A., He, X., Zhang, F., Cristou-Kent, M., Escoffier, J., et al. (2019). Bi-allelic mutations in ARMC2 lead to severe astheno-teratozoospermia due to sperm flagellum malformations in humans and mice. Am J Hum Genet 104, 331–340.
Critchley, H.O.D., and Saunders, P.T.K. (2009). Hormone receptor dynamics in a receptive human endometrium. Reprod Sci 16, 191–199.
Cui, Y., Zheng, Y., Liu, X., Yan, L., Fan, X., Yong, J., Hu, Y., Dong, J., Li, Q., Wu, X., et al. (2019). Single-cell transcriptome analysis maps the developmental track of the human heart. Cell Rep 26, 1934–1950.e5.
Cyranoski, D., and Reardon, S. (2015). Embryo editing sparks epic debate. Nature 520, 593–594.
D’Hooghe, T.M.D., Bambra, C.S., Raeymaekers, B.M., and Koninckx, P.R. (1996). Endometriosis: Increased prevalence and recurrence of retrograde menstruation in baboons with spontaneous endometriosis. Hum Reprod 11, 2022–2025.
Dahanukar, A., Walker, J.A., and Wharton, R.P. (1999). Smaug, a novel RNA-binding protein that operates a translational switch in Drosophila. Mol Cell 4, 209–218.
Dahl, J.A., Jung, I., Aanes, H., Greggains, G.D., Manaf, A., Lerdrup, M., Li, G., Kuan, S., Li, B., Lee, A.Y., et al. (2016). Broad histone H3K4me3 domains in mouse oocytes modulate maternal-to-zygotic transition. Nature 537, 548–552.
Daldello, E.M., Luong, X.G., Yang, C.R., Kuhn, J., and Conti, M. (2019). Cyclin B2 is required for progression through meiosis in mouse oocytes. Development 146, dev172734.
Dalgaard, M.D., Weinhold, N., Edsgärd, D., Silver, J.D., Pers, T.H., Nielsen, J.E., Jørgensen, N., Juul, A., Gerds, T.A., Giwercman, A., et al. (2012). A genome-wide association study of men with symptoms of testicular dysgenesis syndrome and its network biology interpretation. J Med Genet 49, 58–65.
Datta, J., Palmer, M.J., Tanton, C., Gibson, L.J., Jones, K.G., Macdowall, W., Glasier, A., Sonnenberg, P., Field, N., Mercer, C.H., et al. (2016). Prevalence of infertility and help seeking among 15000 women and men. Hum Reprod 31, 2108–2118.
Day, F.R., Hinds, D.A., Tung, J.Y., Stolk, L., Styrkarsdottir, U., Saxena, R., Bjonnes, A., Broer, L., Dunger, D.B., Halldorsson, B.V., et al. (2015). Causal mechanisms and balancing selection inferred from genetic associations with polycystic ovary syndrome. Nat Commun 6, 8464.
De Renzis, S., Elemento, O., Tavazoie, S., and Wieschaus, E.F. (2007). Unmasking activation of the zygotic genome using chromosomal deletions in the Drosophila embryo. PLoS Biol 5, e117.
Defrere, S., Lousse, J.C., Gonzalez-Ramos, R., Colette, S., Donnez, J., and Van Langendonckt, A. (2008). Potential involvement of iron in the pathogenesis of peritoneal endometriosis. Mol Hum Reprod 14, 377–385.
Deiana, D., Gessa, S., Anardu, M., Daniilidis, A., Nappi, L., D’Alterio, M. N., Pontis, A., and Angioni, S. (2019). Genetics of endometriosis: a comprehensive review. Gynecol Endocrinol 35, 553–558.
Dekker, J., and Mirny, L. (2016). The 3D genome as moderator of chromosomal communication. Cell 164, 1110–1121.
Dever, D.P., and Porteus, M.H. (2017). The changing landscape of gene editing in hematopoietic stem cells. Curr Opin Hematol 24, 481–488.
Di Pietro, C. (2016). Exosome-mediated communication in the ovarian follicle. J Assist Reprod Genet 33, 303–311.
Diez-Fraile, A., Lammens, T., Tilleman, K., Witkowski, W., Verhasselt, B., De Sutter, P., Benoit, Y., Espeel, M., and D’Herde, K. (2014). Age-associated differential microRNA levels in human follicular fluid reveal pathways potentially determining fertility and success of in vitro fertilization. Hum Fertil 17, 90–98.
Dirami, T., Rode, B., Jollivet, M., Da Silva, N., Escalier, D., Gaitch, N., Norez, C., Tuffery, P., Wolf, J.P., Becq, F., et al. (2013). Missense mutations in SLC26A8, encoding a sperm-specific activator of CFTR, are associated with human asthenozoospermia. Am J Hum Genet 92, 760–766.
Djokovic, D., and Calhaz-Jorge, C. (2015). Somatic stem cells and their dysfunction in endometriosis. Front Surg 1.
Dmowski, W.P., and Radwanska, E. (1984). Current concepts on pathology, histogenesis and etiology of endometriosis. Acta Obstet Gynecol Scand 63, 29–33.
Du, Y., Liu, X., and Guo, S.W. (2017). Platelets impair natural killer cell reactivity and function in endometriosis through multiple mechanisms. Hum Reprod 32, 794–810.
Du, Z., Zheng, H., Huang, B., Ma, R., Wu, J., Zhang, X., He, J., Xiang, Y., Wang, Q., Li, Y., et al. (2017). Allelic reprogramming of 3D chromatin architecture during early mammalian development. Nature 547, 232–235.
Dumesic, D.A., Abbott, D.H., and Padmanabhan, V. (2007). Polycystic ovary syndrome and its developmental origins. Rev Endocr Metab Disord 8, 127–141.
Echiburu, B., Pérez-Bravo, F., Maliqueo, M., Sánchez, F., Crisosto, N., and Sir-Petermann, T. (2008). Polymorphism T→C (−34 base pairs) of gene CYP17 promoter in women with polycystic ovary syndrome is associated with increased body weight and insulin resistance: a preliminary study. Metabolism 57, 1765–1771.
Eggers, S., and Kirchengast, S. (2001). The polycystic ovary syndrome—a medical condition but also an important psychosocial problem. Coll Antropol 25, 673–685.
Eichenlaub-Ritter, U., Vogt, E., Cukurcam, S., Sun, F., Pacchierotti, F., and Parry, J. (2008). Exposure of mouse oocytes to bisphenol A causes meiotic arrest but not aneuploidy. Mutat Res 651, 82–92.
Eisenberg, I., Nahmias, N., Novoselsky Persky, M., Greenfield, C., Goldman-Wohl, D., Hurwitz, A., Haimov-Kochman, R., Yagel, S., and Imbar, T. (2017). Elevated circulating micro-ribonucleic acid (miRNA)-200b and miRNA-429 levels in anovulatory women. Fertil Steril 107, 269–275.
Elsenbruch, S., Hahn, S., Kowalsky, D., Offner, A.H., Schedlowski, M., Mann, K., and Janssen, O.E. (2003). Quality of life, psychosocial well-being, and sexual satisfaction in women with polycystic ovary syndrome. J Clin Endocrinol Metab 88, 5801–5807.
Ewens, K.G., Stewart, D.R., Ankener, W., Urbanek, M., McAllister, J.M., Chen, C., Baig, K.M., Parker, S.C.J., Margulies, E.H., Legro, R.S., et al. (2010). Family-based analysis of candidate genes for polycystic ovary syndrome. J Clin Endocrinol Metab 95, 2306–2315.
Fayomi, A.P., and Orwig, K.E. (2018). Spermatogonial stem cells and spermatogenesis in mice, monkeys and men. Stem Cell Res 29, 207–214.
Feitosa, W.B., Hwang, K.S., and Morris, P.L. (2018). Temporal and SUMO-specific SUMOylation contribute to the dynamics of Polo-like kinase 1 (PLK1) and spindle integrity during mouse oocyte meiosis. Dev Biol 434, 278–291.
Feitosa, W.B., and Morris, P.L. (2018). SUMOylation regulates germinal vesicle breakdown and the Akt/PKB pathway during mouse oocyte maturation. Am J Physiol Cell Physiol 315, C115–C121.
Feng, C., Lv, P.P., Yu, T.T., Jin, M., Shen, J.M., Wang, X., Zhou, F., and Jiang, S.W. (2015). The association between polymorphism of INSR and polycystic ovary syndrome: a meta-analysis. Int J Mol Sci 16, 2403–2425.
Feng, R., Sang, Q., Kuang, Y., Sun, X., Yan, Z., Zhang, S., Shi, J., Tian, G., Luchniak, A., Fukuda, Y., et al. (2016a). Mutations in TUBB8 and human oocyte meiotic arrest. N Engl J Med 374, 223–232.
Feng, R., Yan, Z., Li, B., Yu, M., Sang, Q., Tian, G., Xu, Y., Chen, B., Qu, R., Sun, Z., et al. (2016b). Mutations in TUBB8 cause a multiplicity of phenotypes in human oocytes and early embryos. J Med Genet 53, 662–671.
Ferlin, A., Rocca, M.S., Vinanzi, C., Ghezzi, M., Di Nisio, A., and Foresta, C. (2015). Mutational screening of NR5A1 gene encoding steroidogenic factor 1 in cryptorchidism and male factor infertility and functional analysis of seven undescribed mutations. Fertil Steril 104, 163–169.e1.
Ferriman, D., and Purdie, A.W. (1979). The inheritance of polycystic ovarian disease and a possible relationship to premature balding. Clin Endocrinol 11, 291–300.
Fesquet, D., Labbe, J., Derancourt, J., Capony, J., Galas, S., Girard, F., Lorca, T., Shuttleworth, J., Doree, M., and Cavadore, J. (1993). The MO15 gene encodes the catalytic subunit of a protein kinase that activates cdc2 and other cyclin-dependent kinases (CDKs) through phosphorylation of Thr161 and its homologues. EMBO J 12, 3111–3121.
Foresta, C., Moro, E., Garolla, A., Onisto, M., and Ferlin, A. (1999). Y Chromosome Microdeletions in Cryptorchidism and Idiopathic Infertility*. J Clin Endocrinol Metab 84, 3660–3665.
Fragouli, E., Alfarawati, S., Goodall, N.N., Sánchez-García, J.F., Colls, P., and Wells, D. (2011). The cytogenetics of polar bodies: insights into female meiosis and the diagnosis of aneuploidy. Mol Hum Reprod 17, 286–295.
Friedli, M., and Trono, D. (2015). The developmental control of transposable elements and the evolution of higher species. Annu Rev Cell Dev Biol 31, 429–451.
Fu, X., He, Y., Wang, X., Peng, D., Chen, X., Li, X., and Wan, Q. (2018). MicroRNA-16 promotes ovarian granulosa cell proliferation and suppresses apoptosis through targeting PDCD4 in polycystic ovarian syndrome. Cell Physiol Biochem 48, 670–682.
Fu, Y., Foden, J.A., Khayter, C., Maeder, M.L., Reyon, D., Joung, J.K., and Sander, J.D. (2013). High-frequency off-target mutagenesis induced by CRISPR-Cas nucleases in human cells. Nat Biotechnol 31, 822–826.
Fu, Y., Sander, J.D., Reyon, D., Cascio, V.M., and Joung, J.K. (2014). Improving CRISPR-Cas nuclease specificity using truncated guide RNAs. Nat Biotechnol 32, 279–284.
Gaasenbeek, M., Powell, B.L., Sovio, U., Haddad, L., Gharani, N., Bennett, A., Groves, C.J., Rush, K., Goh, M.J., Conway, G.S., et al. (2004). Large-Scale analysis of the relationship between CYP11A promoter variation, polycystic ovarian syndrome, and serum testosterone. J Clin Endocrinol Metab 89, 2408–2413.
Gaetje, R., Holtrich, U., Engels, K., Kissler, S., Rody, A., Karn, T., and Kaufmann, M. (2007). Endometriosis may be generated by mimicking the ontogenetic development of the female genital tract. Fertil Steril 87, 651–656.
Galdon, G., Atala, A., and Sadri-Ardekani, H. (2016). In vitro spermatogenesis: how far from clinical application? Curr Urol Rep 17, 49.
Gao, L., Wu, K., Liu, Z., Yao, X., Yuan, S., Tao, W., Yi, L., Yu, G., Hou, Z., Fan, D., et al. (2018). Chromatin accessibility landscape in human early embryos and its association with evolution. Cell 173, 248–259.e15.
Gargett, C.E., Schwab, K.E., Brosens, J.J., Puttemans, P., Benagiano, G., and Brosens, I. (2014). Potential role of endometrial stem/progenitor cells in the pathogenesis of early-onset endometriosis. Mol Hum Reprod 20, 591–598.
Gaudelli, N.M., Komor, A.C., Rees, H.A., Packer, M.S., Badran, A.H., Bryson, D.I., and Liu, D.R. (2017). Programmable base editing of A·T to G·C in genomic DNA without DNA cleavage. Nature 551, 464–471.
Gautier, J., Minshull, J., Lohka, M., Glotzer, M., Hunt, T., and Maller, J.L. (1990). Cyclin is a component of maturation-promoting factor from Xenopus. Cell 60, 487–494.
Geng, Y., Sui, C., Xun, Y., Lai, Q., and Jin, L. (2019). MiRNA-99a can regulate proliferation and apoptosis of human granulosa cells via targeting IGF-1R in polycystic ovary syndrome. J Assist Reprod Genet 36, 211–221.
Gershoni, M., Hauser, R., Yogev, L., Lehavi, O., Azem, F., Yavetz, H., Pietrokovski, S., and Kleiman, S.E. (2017). A familial study of azoospermic men identifies three novel causative mutations in three new human azoospermia genes. Genet Med 19, 998–1006.
Giraldez, A.J., Mishima, Y., Rihel, J., Grocock, R.J., Van Dongen, S., Inoue, K., Enright, A.J., and Schier, A.F. (2006). Zebrafish miR-430 promotes deadenylation and clearance of maternal mRNAs. Science 312, 75–79.
Giudice, L.C., and Kao, L.C. (2004). Endometriosis. Lancet 364, 1789–1799.
Gkountela, S., Zhang, K.X., Shafiq, T.A., Liao, W.W., Hargan-Calvopiña, J., Chen, P.Y., and Clark, A.T. (2015). DNA demethylation dynamics in the human prenatal germline. Cell 161, 1425–1436.
Gluckman, P.D., Hanson, M.A., Buklijas, T., Low, F.M., and Beedle, A.S. (2009). Epigenetic mechanisms that underpin metabolic and cardiovascular diseases. Nat Rev Endocrinol 5, 401–408.
Gonzalez, F., Kirwan, J.P., Rote, N.S., and Minium, J. (2014). Evidence of mononuclear cell preactivation in the fasting state in polycystic ovary syndrome. Am J Obstet Gynecol 211, 635.e1–635.e7.
Goodarzi, M.O. (2008). Looking for polycystic ovary syndrome genes: rational and best strategy. Semin Reprod Med 26, 005–013.
Gootenberg, J.S., Abudayyeh, O.O., Lee, J.W., Essletzbichler, P., Dy, A.J., Joung, J., Verdine, V., Donghia, N., Daringer, N.M., Freije, C.A., et al. (2017). Nucleic acid detection with CRISPR-Cas13a/C2c2. Science 356, 438–442.
Gorbsky, G.J. (2015). The spindle checkpoint and chromosome segregation in meiosis. FEBS J 282, 2471–2487.
Gou, L.T., Kang, J.Y., Dai, P., Wang, X., Li, F., Zhao, S., Zhang, M., Hua, M.M., Lu, Y., Zhu, Y., et al. (2017). Ubiquitination-deficient mutations in human Piwi cause male infertility by impairing histone-to-protamine exchange during spermiogenesis. Obstetr Gynecol Surv 72, 540–541.
Goud, A.P., Goud, P.T., Diamond, M.P., Gonik, B., and Abu-Soud, H.M. (2008). Reactive oxygen species and oocyte aging: role of superoxide, hydrogen peroxide, and hypochlorous acid. Free Rad Biol Med 44, 1295–1304.
Gross, M. (2015). Bacterial scissors to edit human embryos? Curr Biol 25, R439–R442.
Grunewald, J., Zhou, R., Garcia, S.P., Iyer, S., Lareau, C.A., Aryee, M.J., and Joung, J.K. (2019). Transcriptome-wide off-target RNA editing induced by CRISPR-guided DNA base editors. Nature 569, 433–437.
Gu, C., Liu, S., Wu, Q., Zhang, L., and Guo, F. (2019). Integrative single-cell analysis of transcriptome, DNA methylome and chromatin accessibility in mouse oocytes. Cell Res 29, 110–123.
Gu, T.P., Guo, F., Yang, H., Wu, H.P., Xu, G.F., Liu, W., Xie, Z.G., Shi, L., He, X., Jin, S., et al. (2011). The role of Tet3 DNA dioxygenase in epigenetic reprogramming by oocytes. Nature 477, 606–610.
Guerrier, D., Mouchel, T., Pasquier, L., and Pellerin, I. (2006). The Mayer-Rokitansky-Küster-Hauser syndrome (congenital absence of uterus and vagina)—phenotypic manifestations and genetic approaches. J Negat Result Biomed 5, 1.
Guilinger, J.P., Thompson, D.B., and Liu, D.R. (2014). Fusion of catalytically inactive Cas9 to FokI nuclease improves the specificity of genome modification. Nat Biotechnol 32, 577–582.
Guo, F., Yan, L., Guo, H., Li, L., Hu, B., Zhao, Y., Yong, J., Hu, Y., Wang, X., Wei, Y., et al. (2015a). The transcriptome and DNA methylome landscapes of human primordial germ cells. Cell 161, 1437–1452.
Guo, H., Zhu, P., Yan, L., Li, R., Hu, B., Lian, Y., Yan, J., Ren, X., Lin, S., Li, J., et al. (2014). The DNA methylation landscape of human early embryos. Nature 511, 606–610.
Guo, J., Grow, E.J., Mlcochova, H., Maher, G.J., Lindskog, C., Nie, X., Guo, Y., Takei, Y., Yun, J., Cai, L., et al. (2018). The adult human testis transcriptional cell atlas. Cell Res 28, 1141–1157.
Guo, J., Grow, E.J., Yi, C., Mlcochova, H., Maher, G.J., Lindskog, C., Murphy, P.J., Wike, C.L., Carrell, D.T., Goriely, A., et al. (2017). Chromatin and single-cell RNA-Seq profiling reveal dynamic signaling and metabolic transitions during human spermatogonial stem cell development. Cell Stem Cell 21, 533–546.e6.
Guo, R., Zheng, Y., Yang, J., and Zheng, N. (2015). Association of TNF-alpha, IL-6 and IL-1beta gene polymorphisms with polycystic ovary syndrome: a meta-analysis. BMC Genet 16, 5.
Guo, X., Wang, L., Li, J., Ding, Z., Xiao, J., Yin, X., He, S., Shi, P., Dong, L., Li, G., et al. (2015b). Structural insight into autoinhibition and histone H3-induced activation of DNMT3A. Nature 517, 640–644.
Gupta, A., Tiwari, M., Prasad, S., and Chaube, S.K. (2017). Role of cyclic nucleotide phosphodiesterases during meiotic resumption from diplotene arrest in mammalian oocytes. J Cell Biochem 118, 446–452.
Hague, W.M., Adams, J., Rodda, C., Brook, C.G., de Bruyn, R., Grant, D. B., and Jacobs, H.S. (1990). The prevalence of polycystic ovaries in patients with congenital adrenal hyperplasia and their close relatives. Clin Endocrinol 33, 501–510.
Hamatani, T., Carter, M.G., Sharov, A.A., and Ko, M.S.H. (2004). Dynamics of global gene expression changes during mouse preimplantation development. Dev Cell 6, 117–131.
Han, Q., Zhang, W., Meng, J., Ma, L., and Li, A. (2018). LncRNA-LET inhibits cell viability, migration and EMT while induces apoptosis by up-regulation of TIMP2 in human granulosa-like tumor cell line KGN. Biomed Pharmacother 100, 250–256.
Han, S.J., Chen, R., Paronetto, M.P., and Conti, M. (2005). Wee1B is an oocyte-specific kinase involved in the control of meiotic arrest in the mouse. Curr Biol 15, 1670–1676.
Han, S.J., Vaccari, S., Nedachi, T., Andersen, C.B., Kovacina, K.S., Roth, R.A., and Conti, M. (2006). Protein kinase B/Akt phosphorylation of PDE3A and its role in mammalian oocyte maturation. EMBO J 25, 5716–5725.
Hanna, C.W., Taudt, A., Huang, J., Gahurova, L., Kranz, A., Andrews, S., Dean, W., Stewart, A.F., Colomé-Tatché, M., and Kelsey, G. (2018). MLL2 conveys transcription-independent H3K4 trimethylation in oocytes. Nat Struct Mol Biol 25, 73–82.
Hartlerode, A.J., and Scully, R. (2009). Mechanisms of double-strand break repair in somatic mammalian cells. Biochem J 423, 157–168.
Hassold, T., and Hunt, P. (2001). To err (meiotically) is human: the genesis of human aneuploidy. Nat Rev Genet 2, 280–291.
Hayashi, K., Ohta, H., Kurimoto, K., Aramaki, S., and Saitou, M. (2011). Reconstitution of the mouse germ cell specification pathway in culture by pluripotent stem cells. Cell 146, 519–532.
Hayes, M.G., Urbanek, M., Ehrmann, D.A., Armstrong, L.L., Lee, J.Y., Sisk, R., Karaderi, T., Barber, T.M., McCarthy, M.I., Franks, S., et al. (2015). Genome-wide association of polycystic ovary syndrome implicates alterations in gonadotropin secretion in European ancestry populations. Nat Commun 6, 7502.
He, W.B., Tu, C.F., Liu, Q., Meng, L.L., Yuan, S.M., Luo, A.X., He, F.S., Shen, J., Li, W., Du, J., et al. (2018). DMC1 mutation that causes human non-obstructive azoospermia and premature ovarian insufficiency identified by whole-exome sequencing. J Med Genet 349, jmedgenet-2017-104992.
He, X., Li, W., Wu, H., Lv, M., Liu, W., Liu, C., Zhu, F., Li, C., Fang, Y., Yang, C., et al. (2019). Novel homozygous CFAP69 mutations in humans and mice cause severe asthenoteratospermia with multiple morphological abnormalities of the sperm flagella. J Med Genet 56, 96–103.
He, Z.Y., Men, K., Qin, Z., Yang, Y., Xu, T., and Wei, Y.Q. (2017). Non-viral and viral delivery systems for CRISPR-Cas9 technology in the biomedical field. Sci China Life Sci 60, 458–467.
Henckel, A., Chebli, K., Kota, S.K., Arnaud, P., and Feil, R. (2012). Transcription and histone methylation changes correlate with imprint acquisition in male germ cells. EMBO J 31, 606–615.
Hermann, B.P., Cheng, K., Singh, A., Roa-De La Cruz, L., Mutoji, K.N., Chen, I.C., Gildersleeve, H., Lehle, J.D., Mayo, M., Westernströer, B., et al. (2018). The mammalian spermatogenesis single-cell transcriptome, from spermatogonial stem cells to spermatids. Cell Rep 25, 1650–1667.e8.
Hickey, T., Chandy, A., and Norman, R.J. (2002). The androgen receptor CAG repeat polymorphism and X-chromosome inactivation in Australian Caucasian women with infertility related to polycystic ovary syndrome. J Clin Endocrinol Metab 87, 161–165.
Horvath, P., and Barrangou, R. (2010). CRISPR/Cas, the immune system of bacteria and archaea. Science 327, 167–170.
Hsu, P.D., Lander, E.S., and Zhang, F. (2014). Development and applications of CRISPR-Cas9 for genome engineering. Cell 157, 1262–1278.
Hu, Z., Li, Z., Yu, J., Tong, C., Lin, Y., Guo, X., Lu, F., Dong, J., Xia, Y., Wen, Y., et al. (2014). Association analysis identifies new risk loci for non-obstructive azoospermia in Chinese men. Nat Commun 5, 3857.
Hu, Z., Xia, Y., Guo, X., Dai, J., Li, H.G., Hu, H., Jiang, Y., Lu, F., Wu, Y., Yang, X., et al. (2012). A genome-wide association study in Chinese men identifies three risk loci for non-obstructive azoospermia. Nat Genet 44, 183–186.
Huang, C.J., Wu, D., Khan, F.A., and Huo, L.J. (2015a). The SUMO protease SENP3 orchestrates G2-M transition and spindle assembly in mouse oocytes. Sci Rep 5, 15600.
Huang, F., Cao, J., Liu, Q., Zou, Y., Li, H., and Yin, T. (2013). MAPK/ERK signal pathway involved expression of COX-2 and VEGF by IL-1beta induced in human endometriosis stromal cells in vitro. Int J Clin Exp Pathol 6, 2129–2136.
Huang, L., Tong, X., Luo, L., Zheng, S., Jin, R., Fu, Y., Zhou, G., Li, D., and Liu, Y. (2017a). Mutation analysis of the TUBB8 gene in nine infertile women with oocyte maturation arrest. Reproductive Biomed Online 35, 305–310.
Huang, L., Tong, X., Wang, F., Luo, L., Jin, R., Fu, Y., Zhou, G., Li, D., Song, G., Liu, Y., et al. (2018). Novel mutations in PATL2 cause female infertility with oocyte germinal vesicle arrest. Human Reprod 33, 1183–1190.
Huang, N., Wen, Y., Guo, X., Li, Z., Dai, J., Ni, B., Yu, J., Lin, Y., Zhou, W., Yao, B., et al. (2015b). A screen for genomic disorders of infertility identifies MAST2 duplications associated with nonobstructive azoospermia in humans. Biol Reprod 93.
Huang, Z., Tomitaka, A., Raymond, A., and Nair, M. (2017b). Current application of CRISPR/Cas9 gene-editing technique to eradication of HIV/AIDS. Gene Ther 24, 377–384.
Hussin, J., Roy-Gagnon, M.H., Gendron, R., Andelfinger, G., and Awadalla, P. (2011). Age-dependent recombination rates in human pedigrees. PLoS Genet 7, e1002251.
Hwang, J.Y., Lee, E.J., Jin Go, M., Sung, Y.A., Lee, H.J., Heon Kwak, S., Jang, H.C., Soo Park, K., Lee, H.J., Byul Jang, H., et al. (2012). Genome-wide association study identifies GYS2 as a novel genetic factor for polycystic ovary syndrome through obesity-related condition. J Hum Genet 57, 660–664.
Ibanez, L., Potau, N., Francois, I., and de Zegher, F. (1998). Precocious pubarche, hyperinsulinism, and ovarian hyperandrogenism in girls: relation to reduced fetal growth. J Clin Endocrinol Metab 83, 3558–3562.
Inceboz, U. (2015). Endometriosis after menopause. Womens Health (Lond Engl) 11, 711–715.
Ingraham, H.A., Hirokawa, Y., Roberts, L.M., Mellon, S.H., McGee, E., Nachtigal, M.W., and Visser, J.A. (2000). Autocrine and paracrine Mullerian inhibiting substance hormone signaling in reproduction. Recent Prog Horm Res, 55, 53–68.
Irie, N., Weinberger, L., Tang, W.W.C., Kobayashi, T., Viukov, S., Manor, Y.S., Dietmann, S., Hanna, J.H., and Surani, M.A. (2015). SOX17 is a critical specifier of human primordial germ cell fate. Cell 160, 253–268.
Ishii, T. (2017). Germ line genome editing in clinics: the approaches, objectives and global society. Brief Funct Genomics 16, 46–56.
Ishino, Y., Shinagawa, H., Makino, K., Amemura, M., and Nakata, A. (1987). Nucleotide sequence of the iap gene, responsible for alkaline phosphatase isozyme conversion in Escherichia coli, and identification of the gene product. J Bacteriol 169, 5429–5433.
Jafarian, A., Shokri, G., Shokrollahi Barough, M., Moin, M., Pourpak, Z., and Soleimani, M. (2019). Recent advances in gene therapy and modeling of chronic granulomatous disease. Iran J Allergy Asthma Immunol 18, 131–142.
Jahanfar, S., Eden, J.A., Warren, P., Seppälä, M., and Nguyen, T.V. (1995). A twin study of polycystic ovary syndrome. Fertil Steril 63, 478–486.
Jang, M., Lee, M.J., Lee, J.M., Bae, C.S., Kim, S.H., Ryu, J.H., and Cho, I. H. (2014). Oriental medicine Kyung-Ok-Ko prevents and alleviates dehydroepiandrosterone-induced polycystic ovarian syndrome in rats. PLoS ONE 9, e87623.
Jansen, R., Embden, J.D.A., Gaastra, W., and Schouls, L.M. (2002). Identification of genes that are associated with DNA repeats in prokaryotes. Mol Microbiol 43, 1565–1575.
Jiang, F., and Doudna, J.A. (2017). CRISPR-Cas9 structures and mechanisms. Annu Rev Biophys 46, 505–529.
Jiang, L., Huang, J., Chen, Y., Yang, Y., Li, R., Li, Y., Chen, X., and Yang, D. (2016). Identification of several circulating microRNAs from a genome-wide circulating microRNA expression profile as potential biomarkers for impaired glucose metabolism in polycystic ovarian syndrome. Endocrine 53, 280–290.
Jiang, L.L., Xie, J.K., Cui, J.Q., Wei, D., Yin, B.L., Zhang, Y.N., Chen, Y. H., Han, X., Wang, Q., and Zhang, C.L. (2017). Promoter methylation of yes-associated protein (YAP1) gene in polycystic ovary syndrome. Medicine 96, e5768.
Jiang, Y.C., and Ma, J.X. (2018). The role of MiR-324-3p in polycystic ovary syndrome (PCOS) via targeting WNT2B. Eur Rev Med Pharmacol Sci 22, 3286–3293, doi: https://doi.org/10.26355/eurrev_201806_15147.
Jin, L., Yang, Q., Zhou, C., Liu, L., Wang, H., Hou, M., Wu, Y., Shi, F., Sheng, J., and Huang, H. (2018). Profiles for long non-coding RNAs in ovarian granulosa cells from women with PCOS with or without hyperandrogenism. Reprod Biomed Online 37, 613–623.
Jinek, M., Chylinski, K., Fonfara, I., Hauer, M., Doudna, J.A., and Charpentier, E. (2012). A programmable dual-RNA-guided DNA endonuclease in adaptive bacterial immunity. Science 337, 816–821.
Jinek, M., East, A., Cheng, A., Lin, S., Ma, E., and Doudna, J. (2013). RNA-programmed genome editing in human cells. eLife 2, e00471.
Joseph, S., Barai, R.S., Bhujbalrao, R., and Idicula-Thomas, S. (2016). PCOSKB: a KnowledgeBase on genes, diseases, ontology terms and biochemical pathways associated with polycystic ovary syndrome. Nucleic Acids Res 44, D1032–D1035.
Joung, J.K., and Sander, J.D. (2013). TALENs: a widely applicable technology for targeted genome editing. Nat Rev Mol Cell Biol 14, 49–55.
Jukam, D., Shariati, S.A.M., and Skotheim, J.M. (2017). Zygotic genome activation in vertebrates. Dev Cell 42, 316–332.
Junker, J.P., Noël, E.S., Guryev, V., Peterson, K.A., Shah, G., Huisken, J., McMahon, A.P., Berezikov, E., Bakkers, J., and van Oudenaarden, A. (2014). Genome-wide RNA tomography in the zebrafish embryo. Cell 159, 662–675.
Kageyama, S., Liu, H., Kaneko, N., Ooga, M., Nagata, M., and Aoki, F. (2007). Alterations in epigenetic modifications during oocyte growth in mice. Reproduction 133, 85–94.
Kahsar-Miller, M., Boots, L.R., Bartolucci, A., and Azziz, R. (2004). Role of a CYP17 polymorphism in the regulation of circulating dehydroepiandrosterone sulfate levels in women with polycystic ovary syndrome. Fertil Steril 82, 973–975.
Kahsar-Miller, M.D., Nixon, C., Boots, L.R., Go, R.C., and Azziz, R. (2001). Prevalence of polycystic ovary syndrome (PCOS) in first-degree relatives of patients with PCOS. Fertil Steril 75, 53–58.
Kanatsu-Shinohara, M., and Shinohara, T. (2013). Spermatogonial stem cell self-renewal and development. Annu Rev Cell Dev Biol 29, 163–187.
Kang, X., He, W., Huang, Y., Yu, Q., Chen, Y., Gao, X., Sun, X., and Fan, Y. (2016). Introducing precise genetic modifications into human 3PN embryos by CRISPR/Cas-mediated genome editing. J Assist Reprod Genet 33, 581–588.
Kang, Y.J., Jeung, I.C., Park, A., Park, Y.J., Jung, H., Kim, T.D., Lee, H.G., Choi, I., and Yoon, S.R. (2014). An increased level of IL-6 suppresses NK cell activity in peritoneal fluid of patients with endometriosis via regulation of SHP-2 expression. Hum Reprod 29, 2176–2189.
Karasu, M.E., Bouftas, N., Keeney, S., and Wassmann, K. (2019). Cyclin B3 promotes anaphase I onset in oocyte meiosis. J Cell Biol 218, 1265–1281.
Kasak, L., Punab, M., Nagirnaja, L., Grigorova, M., Minajeva, A., Lopes, A.M., Punab, A.M., Aston, K.I., Carvalho, F., Laasik, E., et al. (2018). Bi-allelic recessive loss-of-function variants in FANCM cause non-obstructive azoospermia. Am J Hum Genet 103, 200–212.
Ke, R., Mignardi, M., Pacureanu, A., Svedlund, J., Botling, J., Wählby, C., and Nilsson, M. (2013). In situ sequencing for RNA analysis in preserved tissue and cells. Nat Methods 10, 857–860.
Ke, Y., Xu, Y., Chen, X., Feng, S., Liu, Z., Sun, Y., Yao, X., Li, F., Zhu, W., Gao, L., et al. (2017). 3D chromatin structures of mature gametes and structural reprogramming during mammalian embryogenesis. Cell 170, 367–381.e20.
Kelly, C.C.J., Lyall, H., Petrie, J.R., Gould, G.W., Connell, J.M.C., and Sattar, N. (2001). Low grade chronic inflammation in women with polycystic ovarian syndrome. J Clin Endocrinol Metab 86, 2453–2455.
Kelsey, G., and Feil, R. (2013). New insights into establishment and maintenance of DNA methylation imprints in mammals. Phil Trans R Soc B 368, 20110336.
Kent, S.C., Gnatuk, C.L., Kunselman, A.R., Demers, L.M., Lee, P.A., and Legro, R.S. (2008). Hyperandrogenism and hyperinsulinism in children of women with polycystic ovary syndrome: a controlled study. J Clin Endocrinol Metab 93, 1662–1669.
Kerscher, O. (2007). SUMO junction—what’s your function? New insights through SUMO-interacting motifs. EMBO Rep 8, 550–555.
Khan, F.A., Pandupuspitasari, N.S., Huang, C.J., Hao, X.J., and Zhang, S.J. (2016). SUMOylation: a link to future therapeutics. Curr Issues Mol Biol 18, 49–56.
Kherraf, Z.E., Christou-Kent, M., Karaouzene, T., Amiri-Yekta, A., Martinez, G., Vargas, A.S., Lambert, E., Borel, C., Dorphin, B., Aknin-Seifer, I., et al. (2017). SPINK 2 deficiency causes infertility by inducing sperm defects in heterozygotes and azoospermia in homozygotes. EMBO Mol Med 9, 1132–1149.
Kim, D., Kim, D.E., Lee, G., Cho, S.I., and Kim, J.S. (2019). Genome-wide target specificity of CRISPR RNA-guided adenine base editors. Nat Biotechnol 37, 430–435.
Kim, D., Lim, K., Kim, S.T., Yoon, S.H., Kim, K., Ryu, S.M., and Kim, J.S. (2017). Genome-wide target specificities of CRISPR RNA-guided programmable deaminases. Nat Biotechnol 35, 475–480.
Klemmt, P.A.B., and Starzinski-Powitz, A. (2018). Molecular and cellular pathogenesis of endometriosis. Curr Womens Health Res 14, 106–116.
Knott, G.J., and Doudna, J.A. (2018). CRISPR-Cas guides the future of genetic engineering. Science 361, 866–869.
Kobayashi, H., Sakurai, T., Imai, M., Takahashi, N., Fukuda, A., Yayoi, O., Sato, S., Nakabayashi, K., Hata, K., Sotomaru, Y., et al. (2012). Contribution of intragenic DNA methylation in mouse gametic DNA methylomes to establish oocyte-specific heritable marks. PLoS Genet 8, e1002440.
Koga, K., Osuga, Y., Yoshino, O., Hirota, Y., Yano, T., Tsutsumi, O., and Taketani, Y. (2005). Elevated interleukin-16 levels in the peritoneal fluid of women with endometriosis may be a mechanism for inflammatory reactions associated with endometriosis. Fertil Steril 83, 878–882.
Kokosar, M., Benrick, A., Perfilyev, A., Fornes, R., Nilsson, E., Maliqueo, M., Behre, C.J., Sazonova, A., Ohlsson, C., Ling, C., et al. (2016). Epigenetic and transcriptional alterations in human adipose tissue of polycystic ovary syndrome. Sci Rep 6, 22883.
Komor, A.C., Kim, Y.B., Packer, M.S., Zuris, J.A., and Liu, D.R. (2016). Programmable editing of a target base in genomic DNA without double-stranded DNA cleavage. Nature 533, 420–424.
Kong, F., Du, C., and Wang, Y. (2019). MicroRNA-9 affects isolated ovarian granulosa cells proliferation and apoptosis via targeting vitamin D receptor. Mol Cell Endocrinol 486, 18–24.
Koukoura, O., Sifakis, S., and Spandidos, D.A. (2016). DNA methylation in endometriosis. Mol Med Rep 13, 2939–2948.
Krausz, C., Giachini, C., Lo Giacco, D., Daguin, F., Chianese, C., Ars, E., Ruiz-Castane, E., Forti, G., and Rossi, E. (2012). High resolution X chromosome-specific array-CGH detects new CNVs in infertile males. PLoS ONE 7, e44887.
Krausz, C., and Riera-Escamilla, A. (2018). Genetics of male infertility. Nat Rev Urol 15, 369–384.
Kubiak, J.Z., Weber, M., de Pennart, H., Winston, N.J., and Maro, B. (1993). The metaphase II arrest in mouse oocytes is controlled through microtubule-dependent destruction of cyclin B in the presence of CSF. EMBO J 12, 3773–3778.
Kuliev, A., Zlatopolsky, Z., Kirillova, I., Spivakova, J., and Cieslak Janzen, J. (2011). Meiosis errors in over 20,000 oocytes studied in the practice of preimplantation aneuploidy testing. Reprod Biomed Online 22, 2–8.
Kuscu, C., Arslan, S., Singh, R., Thorpe, J., and Adli, M. (2014). Genome-wide analysis reveals characteristics of off-target sites bound by the Cas9 endonuclease. Nat Biotechnol 32, 677–683.
Kusz-Zamelczyk, K., Sajek, M., Spik, A., Glazar, R., Jędrzejczak, P., Latos-Bieleńska, A., Kotecki, M., Pawelczyk, L., and Jaruzelska, J. (2013). Mutations of NANOS1, a human homologue of the Drosophila morphogen, are associated with a lack of germ cells in testes or severe oligo-astheno-teratozoospermia. J Med Genet 50, 187–193.
Lander, E.S. (2016). The heroes of CRISPR. Cell 164, 18–28.
Lattuada, D., Somigliana, E., Viganò, P., Candiani, M., Pardi, G., and Di Blasio, A.M. (2004). Genetics of endometriosis: a role for the progesterone receptor gene polymorphism PROGINS? Clin Endocrinol 61, 190–194.
LaVoie, H.A. (2005). Epigenetic control of ovarian function: The emerging role of histone modifications. Mol Cell Endocrinol 243, 12–18.
Lazzarotto, C.R., Nguyen, N.T., Tang, X., Malagon-Lopez, J., Guo, J.A., Aryee, M.J., Joung, J.K., and Tsai, S.Q. (2018). Defining CRISPR-Cas9 genome-wide nuclease activities with CIRCLE-seq. Nat Protoc 13, 2615–2642.
Lebovic, D.I., Mueller, M.D., and Taylor, R.N. (2001). Immunobiology of endometriosis. Fertil Steril 75, 1–10.
Lee, H., Oh, J.Y., Sung, Y.A., Chung, H., Kim, H.L., Kim, G.S., Cho, Y.S., and Kim, J.T. (2015). Genome-wide association study identified new susceptibility loci for polycystic ovary syndrome. Hum Reprod 30, 723–731.
Lee, J., Kitajima, T.S., Tanno, Y., Yoshida, K., Morita, T., Miyano, T., Miyake, M., and Watanabe, Y. (2008). Unified mode of centromeric protection by shugoshin in mammalian oocytes and somatic cells. Nat Cell Biol 10, 42–52.
Lee, J.H., Daugharthy, E.R., Scheiman, J., Kalhor, R., Yang, J.L., Ferrante, T.C., Terry, R., Jeanty, S.S.F., Li, C., Amamoto, R., et al. (2014a). Highly multiplexed subcellular RNA sequencing in situ. Science 343, 1360–1363.
Lee, K. (2017). Zygotic Genome Activation: Methods and Protocols (New York: Humana Press).
Lee, M.T., Bonneau, A.R., and Giraldez, A.J. (2014b). Zygotic genome activation during the maternal-to-zygotic transition. Annu Rev Cell Dev Biol 30, 581–613.
Lefebvre, C., Terret, M.E., Djiane, A., Rassinier, P., Maro, B., and Verlhac, M.H. (2002). Meiotic spindle stability depends on MAPK-interacting and spindle-stabilizing protein (MISS), a new MAPK substrate. J Cell Biol 157, 603–613.
Legro, R.S., Driscoll, D., Strauss, J.F., Fox, J., and Dunaif, A. (1998). Evidence for a genetic basis for hyperandrogenemia in polycystic ovary syndrome. Proc Natl Acad Sci USA 95, 14956–14960.
Lescroart, F., Wang, X., Lin, X., Swedlund, B., Gargouri, S., Sànchez-Dànes, A., Moignard, V., Dubois, C., Paulissen, C., Kinston, S., et al. (2018). Defining the earliest step of cardiovascular lineage segregation by single-cell RNA-seq. Science 359, 1177–1181.
Llano, E., Gómez, R., Gutiérrez-Caballero, C., Herrán, Y., Sánchez-Martín, M., Vázquez-Quiñones, L., Hernández, T., de Alava, E., Cuadrado, A., Barbero, J.L., et al. (2008). Shugoshin-2 is essential for the completion of meiosis but not for mitotic cell division in mice. Genes Dev 22, 2400–2413.
Li, B.Z., Huang, Z., Cui, Q.Y., Song, X.H., Du, L., Jeltsch, A., Chen, P., Li, G., Li, E., and Xu, G.L. (2011). Histone tails regulate DNA methylation by allosterically activating de novo methyltransferase. Cell Res 21, 1172–1181.
Li, C., Guan, X., Du, T., Jin, W., Wu, B., Liu, Y., Wang, P., Hu, B., Griffin, G.E., Shattock, R.J., et al. (2015a). Inhibition of HIV-1 infection of primary CD4+ T-cells by gene editing of CCR5 using adenovirus-delivered CRISPR/Cas9. J Gen Virol 30, 2381–2393.
Li, E. (2002). Chromatin modification and epigenetic reprogramming in mammalian development. Nat Rev Genet 3, 662–673.
Li, G., Liu, Y., Zeng, Y., Li, J., Wang, L., Yang, G., Chen, D., Shang, X., Chen, J., Huang, X., et al. (2017a). Highly efficient and precise base editing in discarded human tripronuclear embryos. Protein Cell 8, 776–779.
Li, G., Yu, Y., Fan, Y., Li, C., Xu, X., Duan, J., Li, R., Kang, X., Ma, X., Chen, X., et al. (2017b). Genome wide abnormal DNA methylome of human blastocyst in assisted reproductive technology. J Genet Genomics 44, 475–481.
Li, J., Tang, J.X., Cheng, J.M., Hu, B., Wang, Y.Q., Aalia, B., Li, X.Y., Jin, C., Wang, X.X., Deng, S.L., et al. (2018a). Cyclin B2 can compensate for Cyclin B1 in oocyte meiosis I. J Cell Biol 217, 3901–3911.
Li, L., Dong, J., Yan, L., Yong, J., Liu, X., Hu, Y., Fan, X., Wu, X., Guo, H., Wang, X., et al. (2017c). Single-cell RNA-Seq analysis maps development of human germline cells and gonadal niche interactions. Cell Stem Cell 20, 858–873.e4.
Li, S., Zhu, D., Duan, H., Ren, A., Glintborg, D., Andersen, M., Skov, V., Thomassen, M., Kruse, T., and Tan, Q. (2017d). Differential DNA methylation patterns of polycystic ovarian syndrome in whole blood of Chinese women. Oncotarget 8.
Li, Y., Wang, L., Zhang, L., He, Z., Feng, G., Sun, H., Wang, J., Li, Z., Liu, C., Han, J., et al. (2019a). Cyclin B3 is required for metaphase to anaphase transition in oocyte meiosis I. J Cell Biol 218, 1553–1563.
Li, Y., Zhang, Z., Chen, J., Liu, W., Lai, W., Liu, B., Li, X., Liu, L., Xu, S., Dong, Q., et al. (2018b). Stella safeguards the oocyte methylome by preventing de novo methylation mediated by DNMT1. Nature 564, 136–140.
Li, Y., Zhao, W., Wang, H., Chen, C., Zhou, D., Li, S., Zhang, X., Zhao, H., Zhou, D., and Chen, B. (2019b). Silencing of lncRNA steroid receptor RNA activator attenuates polycystic ovary syndrome in mice. Biochimie 157, 48–56.
Li, Y.R., Peng, R.R., Gao, W.Y., Liu, P., Chen, L.J., Zhang, X.L., Zhang, N. N., Wang, Y., Du, L., Zhu, F.Y., et al. (2019c). The ubiquitin ligase KBTBD8 regulates PKM1 levels via Erk1/2 and Aurora A to ensure oocyte quality. Aging 11, 1110–1128.
Li, Z., Huang, Y., Li, H., Hu, J., Liu, X., Jiang, T., Sun, G., Tang, A., Sun, X., Qian, W., et al. (2015b). Excess of rare variants in genes that are key epigenetic regulators of spermatogenesis in the patients with non-obstructive azoospermia. Sci Rep 5, 8785.
Lieber, M.R. (2010). The mechanism of double-strand DNA break repair by the nonhomologous DNA end-joining pathway. Annu Rev Biochem 79, 181–211.
Lieber, M.R., and Karanjawala, Z.E. (2004). Ageing, repetitive genomes and DNA damage. Nat Rev Mol Cell Biol 5, 69–75.
Lieber, M.R., Ma, Y., Pannicke, U., and Schwarz, K. (2003). Mechanism and regulation of human non-homologous DNA end-joining. Nat Rev Mol Cell Biol 4, 712–720.
Lin, H., Xing, W., Li, Y., Xie, Y., Tang, X., and Zhang, Q. (2018). Downregulation of serum long noncoding RNA GAS5 may contribute to insulin resistance in PCOS patients. Gynecol Endocrinol 34, 784–788.
Lin, L., Du, T., Huang, J., Huang, L.L., and Yang, D.Z. (2015). Identification of differentially expressed microRNAs in the ovary of polycystic ovary syndrome with hyperandrogenism and insulin resistance. Chin Med J 128, 169–174.
Lindstrom, N.O., McMahon, J.A., Guo, J., Tran, T., Guo, Q., Rutledge, E., Parvez, R.K., Saribekyan, G., Schuler, R.E., Liao, C., et al. (2018). Conserved and divergent features of human and mouse kidney organogenesis. J Am Soc Nephrol 29, ASN.2017080887.
Liu, L., Li, S., Li, H., Yu, D., Li, C., Li, G., Cao, Y., Feng, C., and Deng, X. (2018). Protein kinase C5 (PKC5) involved in the regulation of pAkt1 (Ser473) on the release of mouse oocytes from diplotene arrest. Cell Biochem Funct 36, 221–227.
Liu, X., Wang, C., Liu, W., Li, J., Li, C., Kou, X., Chen, J., Zhao, Y., Gao, H., Wang, H., et al. (2016). Distinct features of H3K4me3 and H3K27me3 chromatin domains in pre-implantation embryos. Nature 537, 558–562.
Liu, Y.D., Li, Y., Feng, S.X., Ye, D.S., Chen, X., Zhou, X.Y., and Chen, S. L. (2017a). Long noncoding RNAs: potential regulators involved in the pathogenesis of polycystic ovary syndrome. Endocrinology 158, 3890–3899.
Liu, Z., Chen, S., Jin, X., Wang, Q., Yang, K., Li, C., Xiao, Q., Hou, P., Liu, S., Wu, S., et al. (2017b). Genome editing of the HIV co-receptors CCR5 and CXCR4 by CRISPR-Cas9 protects CD4+ T cells from HIV-1 infection. Cell Biosci 7, 47.
Lo Giacco, D., Chianese, C., Ars, E., Ruiz-Castañé, E., Forti, G., and Krausz, C. (2014). Recurrent X chromosome-linked deletions: discovery of new genetic factors in male infertility. J Med Genet 51, 340–344.
Lopes, A.M., Aston, K.I., Thompson, E., Carvalho, F., Gonçalves, J., Huang, N., Matthiesen, R., Noordam, M.J., Quintela, I., Ramu, A., et al. (2013). Human spermatogenic failure purges deleterious mutation load from the autosomes and both sex chromosomes, including the gene DMRT1. PLoS Genet 9, e1003349.
Lovatt, D., Ruble, B.K., Lee, J., Dueck, H., Kim, T.K., Fisher, S., Francis, C., Spaethling, J.M., Wolf, J.A., Grady, M.S., et al. (2014). Transcriptome in vivo analysis (TIVA) of spatially defined single cells in live tissue. Nat Methods 11, 190–196.
Lu, S., Zong, C., Fan, W., Yang, M., Li, J., Chapman, A.R., Zhu, P., Hu, X., Xu, L., Yan, L., et al. (2012). Probing meiotic recombination and aneuploidy of single sperm cells by whole-genome sequencing. Science 338, 1627–1630.
Lu, F., Liu, Y., Inoue, A., Suzuki, T., Zhao, K., and Zhang, Y. (2016). Establishing chromatin regulatory landscape during mouse preimplantation development. Cell 165, 1375–1388.
Lubeck, E., Coskun, A.F., Zhiyentayev, T., Ahmad, M., and Cai, L. (2014). Single-cell in situ RNA profiling by sequential hybridization. Nat Methods 11, 360–361.
Lucifero, D., Mann, M.R.W., Bartolomei, M.S., and Trasler, J.M. (2004). Gene-specific timing and epigenetic memory in oocyte imprinting. Hum Mol Genet 13, 839–849.
Lunde, O., Magnus, P., Sandvik, L., and Hoglo, S. (1989). Familial clustering in the polycystic ovarian syndrome. Gynecol Obstet Invest 28, 23–30.
Lundgren, K., Walworth, N., Booher, R., Dembski, M., Kirschner, M., and Beach, D. (1991). Mik1 and Wee1 cooperate in the inhibitory tyrosine phosphorylation of Cdc2. Cell 64, 1111–1122.
Ma, H., Marti-Gutierrez, N., Park, S.W., Wu, J., Lee, Y., Suzuki, K., Koski, A., Ji, D., Hayama, T., Ahmed, R., et al. (2017). Correction of a pathogenic gene mutation in human embryos. Nature 548, 413–419.
Ma, P., Pan, H., Montgomery, R.L., Olson, E.N., and Schultz, R.M. (2012). Compensatory functions of histone deacetylase 1 (HDAC1) and HDAC2 regulate transcription and apoptosis during mouse oocyte development. Proc Natl Acad Sci USA 109, E481–E489.
Ma, Q., Li, Y., Guo, H., Li, C., Chen, J., Luo, M., Jiang, Z., Li, H., and Gui, Y. (2016a). A novel missense mutation in USP26 gene is associated with nonobstructive azoospermia. Reprod Sci 23, 1434–1441.
Ma, Y., Zhang, J., Yin, W., Zhang, Z., Song, Y., and Chang, X. (2016b). Targeted AID-mediated mutagenesis (TAM) enables efficient genomic diversification in mammalian cells. Nat Methods 13, 1029–1035.
Ma, Z., Zhao, H., Zhang, Y., Liu, X., and Hao, C. (2019). Novel circular RNA expression in the cumulus cells of patients with polycystic ovary syndrome. Arch Gynecol Obstet 299, 1715–1725.
Machtinger, R., Laurent, L.C., and Baccarelli, A.A. (2015). Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Hum Reprod Update 984, dmv055.
Machtinger, R., Rodosthenous, R.S., Adir, M., Mansour, A., Racowsky, C., Baccarelli, A.A., and Hauser, R. (2017). Extracellular microRNAs in follicular fluid and their potential association with oocyte fertilization and embryo quality: an exploratory study. J Assist Reprod Genet 34, 525–533.
Maddirevula, S., Coskun, S., Alhassan, S., Elnour, A., Alsaif, H.S., Ibrahim, N., Abdulwahab, F., Arold, S.T., and Alkuraya, F.S. (2017). Female infertility caused by mutations in the oocyte-specific translational repressor PATL2. Am J Hum Genet 101, 603–608.
Madgwick, S., and Jones, K.T. (2007). How eggs arrest at metaphase II: MPF stabilisation plus APC/C inhibition equals cytostatic factor. Cell Div 2, 4.
Maenohara, S., Unoki, M., Toh, H., Ohishi, H., Sharif, J., Koseki, H., and Sasaki, H. (2017). Role of UHRF1 in de novo DNA methylation in oocytes and maintenance methylation in preimplantation embryos. PLoS Genet 13, e1007042.
Mali, P., Esvelt, K.M., and Church, G.M. (2013a). Cas9 as a versatile tool for engineering biology. Nat Methods 10, 957–963.
Mali, P., Yang, L., Esvelt, K.M., Aach, J., Guell, M., DiCarlo, J.E., Norville, J.E., and Church, G.M. (2013b). RNA-guided human genome engineering via Cas9. Science 339, 823–826.
Maor-Sagie, E., Cinnamon, Y., Yaacov, B., Shaag, A., Goldsmidt, H., Zenvirt, S., Laufer, N., Richler, C., and Frumkin, A. (2015). Deleterious mutation in SYCE1 is associated with non-obstructive azoospermia. J Assist Reprod Genet 32, 887–891.
Marco, A. (2017). Clearance of maternal RNAs: not a Mummy’s embryo anymore. Methods Mol Biol 1605, 1–10.
Martin, G.M., Smith, A.C., Ketterer, D.J., Ogburn, C.E., and Disteche, C. M. (1985). Increased chromosomal aberrations in first metaphases of cells isolated from the kidneys of aged mice. Isr J Med Sci 21, 296–301.
Martinez, R.M., Liang, L., Racowsky, C., Dioni, L., Mansur, A., Adir, M., Bollati, V., Baccarelli, A.A., Hauser, R., and Machtinger, R. (2018). Extracellular microRNAs profile in human follicular fluid and IVF outcomes. Sci Rep 8, 17036.
Kaneda, M., Okano, M., Hata, K., Sado, T., Tsujimoto, N., Li, E., and Sasaki, H. (2004). Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature 429, 900–903.
Masui, Y., and Markert, C.L. (1971). Cytoplasmic control of nuclear behavior during meiotic maturation of frog oocytes. J Exp Zool 177, 129–145.
Mayerhofer, A. (2013). Human testicular peritubular cells: more than meets the eye. Reproduction 145, R107–R116.
McCartney, C.R., and Marshall, J.C. (2016). Polycystic ovary syndrome. N Engl J Med 375, 54–64.
Mellor, H., and Parker, P.J. (1998). The extended protein kinase C superfamily. Biochem J 332, 281–292.
Men, K., Duan, X., He, Z., Yang, Y., Yao, S., and Wei, Y. (2017). CRISPR/Cas9-mediated correction of human genetic disease. Sci China Life Sci 60, 447–457.
Messerschmidt, D.M., de Vries, W., Ito, M., Solter, D., Ferguson-Smith, A., and Knowles, B.B. (2012). Trim28 is required for epigenetic stability during mouse oocyte to embryo transition. Science 335, 1499–1502.
Mettananda, S., Fisher, C.A., Hay, D., Badat, M., Quek, L., Clark, K., Hublitz, P., Downes, D., Kerry, J., Gosden, M., et al. (2017). Editing an α-globin enhancer in primary human hematopoietic stem cells as a treatment for β-thalassemia. Nat Commun 8, 424.
Mettananda, S., Gibbons, R.J., and Higgs, D.R. (2015). α-Globin as a molecular target in the treatment of β-thalassemia. Blood 125, 3694–3701.
Miao, Y.L., Kikuchi, K., Sun, Q.Y., and Schatten, H. (2009). Oocyte aging: cellular and molecular changes, developmental potential and reversal possibility. Hum Reprod Update 15, 573–585.
Mifsud, A., Ramirez, S., and Yong, E.L. (2000). Androgen receptor gene CAG trinucleotide repeats in anovulatory infertility and polycystic ovaries. J Clin Endocrinol Metab 85, 3484–3488.
Mihajlović, A.I., and FitzHarris, G. (2018). Segregating chromosomes in the mammalian oocyte. Curr Biol 28, R895–R907.
Minkenberg, B., Wheatley, M., and Yang, Y. (2017). CRISPR/Cas9-Enabled Multiplex Genome Editing and Its Application. Prog Mol Biol Transl Sci 149, 111–132.
Miyamoto, T., Bando, Y., Koh, E., Tsujimura, A., Miyagawa, Y., Iijima, M., Namiki, M., Shiina, M., Ogata, K., Matsumoto, N., et al. (2016). A PLK4 mutation causing azoospermia in a man with Sertoli cell-only syndrome. Andrology 4, 75–81.
Miyamoto, T., Hasuike, S., Yogev, L., Maduro, M.R., Ishikawa, M., Westphal, H., and Lamb, D.J. (2003). Azoospermia in patients heterozygous for a mutation in SYCP3. Lancet 362, 1714–1719.
Mojica, F.J.M., Diez-Villasenor, C., Soria, E., and Juez, G. (2000). Biological significance of a family of regularly spaced repeats in the genomes of archaea, bacteria and mitochondria. Mol Microbiol 36, 244–246.
Mojica, F.J.M., Ferrer, C., Juez, G., and Rodriguez-Valera, F. (1995). Long stretches of short tandem repeats are present in the largest replicons of the archaea Haloferax mediterranei and Haloferax volcanii and could be involved in replicon partitioning. Mol Microbiol 17, 85–93.
Mozdarani, H., Ghoraeian, P., Mozdarani, S., Fallahi, P., and Mohseni-Meybodi, A. (2018). High frequency of de novo DAZ microdeletion in sperm nuclei of subfertile men: possible involvement of genome instability in idiopathic male infertility. Hum Fertil 21, 137–145.
Mueller, P.R., Coleman, T.R., Kumagai, A., and Dunphy, W.G. (1995). Myt1: a membrane-associated inhibitory kinase that phosphorylates Cdc2 on both threonine-14 and tyrosine-15. Science 270, 86–90.
Munger, S.C., Natarajan, A., Looger, L.L., Ohler, U., and Capel, B. (2013). Fine time course expression analysis identifies cascades of activation and repression and maps a putative regulator of mammalian sex determination. PLoS Genet 9, e1003630.
Murri, M., Insenser, M., Fernández-Durán, E., San-Millán, J.L., Luque-Ramírez, M., and Escobar-Morreale, H.F. (2018). Non-targeted profiling of circulating microRNAs in women with polycystic ovary syndrome (PCOS): effects of obesity and sex hormones. Metabolism 86, 49–60.
Musunuru, K. (2017). The hope and hype of CRISPR-Cas9 genome editing. JAMA Cardiol 2, 914–919.
Nakamura, S., Miyado, M., Saito, K., Katsumi, M., Nakamura, A., Kobori, Y., Tanaka, Y., Ishikawa, H., Yoshida, A., Okada, H., et al. (2017). Next-generation sequencing for patients with non-obstructive azoospermia: implications for significant roles of monogenic/oligogenic mutations. Andrology 5, 824–831.
Nashun, B., Hill, P.W.S., Smallwood, S.A., Dharmalingam, G., Amouroux, R., Clark, S.J., Sharma, V., Ndjetehe, E., Pelczar, P., Festenstein, R.J., et al. (2015). Continuous histone replacement by Hira is essential for normal transcriptional regulation and de novo DNA methylation during mouse oogenesis. Mol Cell 60, 611–625.
Niakan, K.K., and Eggan, K. (2013). Analysis of human embryos from zygote to blastocyst reveals distinct gene expression patterns relative to the mouse. Dev Biol 375, 54–64.
Niccoli, G., Apa, R., Lanzone, A., Liuzzo, G., Spaziani, C., Sagnella, F., Cosentino, N., Moro, F., Martinez, D., Morciano, A., et al. (2011). CD4+CD28null T lymphocytes are expanded in young women with polycystic ovary syndrome. Fertil Steril 95, 2651–2654.
Niederberger, C. (2018). Re: Correction of a pathogenic gene mutation in human embryos. J Urol 199, 330–332.
Nilsson, E., Benrick, A., Kokosar, M., Krook, A., Lindgren, E., Källman, T., Martis, M.M., Højlund, K., Ling, C., and Stener-Victorin, E. (2018). Transcriptional and epigenetic changes influencing skeletal muscle metabolism in women with polycystic ovary syndrome. J Clin Endocrinol Metab 103, 4465–4477.
Nishida, K., Arazoe, T., Yachie, N., Banno, S., Kakimoto, M., Tabata, M., Mochizuki, M., Miyabe, A., Araki, M., Hara, K.Y., et al. (2016). Targeted nucleotide editing using hybrid prokaryotic and vertebrate adaptive immune systems. Science 353, aaf8729.
Nishimasu, H., Ran, F.A., Hsu, P.D., Konermann, S., Shehata, S.I., Dohmae, N., Ishitani, R., Zhang, F., and Nureki, O. (2014). Crystal structure of Cas9 in complex with guide RNA and target DNA. Cell 156, 935–949.
Niwa, H., Toyooka, Y., Shimosato, D., Strumpf, D., Takahashi, K., Yagi, R., and Rossant, J. (2005). Interaction between Oct3/4 and Cdx2 determines trophectoderm differentiation. Cell 123, 917–929.
Norris, R.P., Freudzon, M., Mehlmann, L.M., Cowan, A.E., Simon, A.M., Paul, D.L., Lampe, P.D., and Jaffe, L.A. (2008). Luteinizing hormone causes MAP kinase-dependent phosphorylation and closure of connexin 43 gap junctions in mouse ovarian follicles: one of two paths to meiotic resumption. Development 135, 3229–3238.
Nowotschin, S., Setty, M., Kuo, Y.Y., Liu, V., Garg, V., Sharma, R., Simon, C.S., Saiz, N., Gardner, R., Boutet, S.C., et al. (2019). The emergent landscape of the mouse gut endoderm at single-cell resolution. Nature 569, 361–367.
O’Doherty, A.M., O’Brien, Y.M., Browne, J.A., Wingfield, M., and O’Shea, L.C. (2018). Expression of granulosa cell microRNAs, AVEN and ATRX are associated with human blastocyst development. Mol Reprod Dev 85, 836–848.
Okano, M., Bell, D.W., Haber, D.A., and Li, E. (1999). DNA methyltransferases Dnmt3a and Dnmt3b are essential for de novo methylation and mammalian development. Cell 99, 247–257.
Okutman, O., Muller, J., Baert, Y., Serdarogullari, M., Gultomruk, M., Piton, A., Rombaut, C., Benkhalifa, M., Teletin, M., Skory, V., et al. (2015). Exome sequencing reveals a nonsense mutation in TEX15 causing spermatogenic failure in a Turkish family. Hum Mol Genet 24, 5581–5588.
Okutman, O., Muller, J., Skory, V., Garnier, J.M., Gaucherot, A., Baert, Y., Lamour, V., Serdarogullari, M., Gultomruk, M., Röpke, A., et al. (2017). A no-stop mutation in MAGEB4 is a possible cause of rare X-linked azoospermia and oligozoospermia in a consanguineous Turkish family. J Assist Reprod Genet 34, 683–694.
Oliva, R. (2006). Protamines and male infertility. Hum Reprod Update 12, 417–435.
Pacchierotti, F., Adler, I.D., Eichenlaub-Ritter, U., and Mailhes, J.B. (2007). Gender effects on the incidence of aneuploidy in mammalian germ cells. Environ Res 104, 46–69.
Pan, B., and Li, J. (2019). The art of oocyte meiotic arrest regulation. Reprod Biol Endocrinol 17, 8.
Pan, H., Ma, P., Zhu, W., and Schultz, R.M. (2008). Age-associated increase in aneuploidy and changes in gene expression in mouse eggs. Dev Biol 316, 397–407.
Pan, J.X., Tan, Y.J., Wang, F.F., Hou, N.N., Xiang, Y.Q., Zhang, J.Y., Liu, Y., Qu, F., Meng, Q., Xu, J., et al. (2018). Aberrant expression and DNA methylation of lipid metabolism genes in PCOS: a new insight into its pathogenesis. Clin Epigenet 10, 6.
Panir, K., Schjenken, J.E., Robertson, S.A., and Hull, M.L. (2018). Non-coding RNAs in endometriosis: a narrative review. Hum Reprod Update 24, 497–515.
Paques, F., and Haber, J.E. (1999). Multiple pathways of recombination induced by double-strand breaks in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 63, 349–404.
Parker, L.L., and Piwnica-Worms, H. (1992). Inactivation of the p34cdc2-cyclin B complex by the human WEE1 tyrosine kinase. Science 257, 1955–1957.
Pellestor, F., Andréo, B., Anahory, T., and Hamamah, S. (2006). The occurrence of aneuploidy in human: lessons from the cytogenetic studies of human oocytes. Eur J Med Genets 49, 103–116.
Peng, G., Suo, S., Chen, J., Chen, W., Liu, C., Yu, F., Wang, R., Chen, S., Sun, N., Cui, G., et al. (2016). Spatial transcriptome for the molecular annotation of lineage fates and cell identity in mid-gastrula mouse embryo. Dev Cell 36, 681–697.
Perry, A.C.F., and Verlhac, M.H. (2008). Second meiotic arrest and exit in frogs and mice. EMBO Rep 9, 246–251.
Petropoulos, S., Edsgärd, D., Reinius, B., Deng, Q., Panula, S.P., Codeluppi, S., Plaza Reyes, A., Linnarsson, S., Sandberg, R., and Lanner, F. (2016). Single-cell RNA-Seq reveals lineage and X chromosome dynamics in human preimplantation embryos. Cell 165, 1012–1026.
Petry, C.J., Ong, K.K., Michelmore, K.F., Artigas, S., Wingate, D.L., Balen, A.H., de Zegher, F., Ibáñez, L., and Dunger, D.B. (2005). Association of aromatase (CYP 19) gene variation with features of hyperandrogenism in two populations of young women. Hum Reprod 20, 1837–1843.
Petry, C.J., Ong, K.K., Michelmore, K.F., Artigas, S., Wingate, D.L., Balen, A.H., de Zegher, F., Ibáñez, L., and Dunger, D.B. (2006). Associations between common variation in the aromatase gene promoter region and testosterone concentrations in two young female populations. J Steroid Biochem Mol Biol 98, 199–206.
Pijuan-Sala, B., Griffiths, J.A., Guibentif, C., Hiscock, T.W., Jawaid, W., Calero-Nieto, F.J., Mulas, C., Ibarra-Soria, X., Tyser, R.C.V., Ho, D.L. L., et al. (2019). A single-cell molecular map of mouse gastrulation and early organogenesis. Nature 566, 490–495.
Pisarska, M.D., Chan, J.L., Lawrenson, K., Gonzalez, T.L., and Wang, E.T. (2019). Genetics and epigenetics of infertility and treatments on outcomes. J Clin Endocrinol Metab 104, 1871–1886.
Porcher, C., Swat, W., Rockwell, K., Fujiwara, Y., Alt, F.W., and Orkin, S. H. (1996). The T cell leukemia oncoprotein SCL/tal-1 is essential for development of all hematopoietic lineages. Cell 86, 47–57.
Porpora, M.G., Ingelido, A.M., di Domenico, A., Ferro, A., Crobu, M., Pallante, D., Cardelli, M., Cosmi, E.V., and De Felip, E. (2006). Increased levels of polychlorobiphenyls in Italian women with endometriosis. Chemosphere 63, 1361–1367.
Porteus, M.H., and Dann, C.T. (2015). Genome editing of the germline: broadening the discussion. Mol Ther 23, 980–982.
Prince, F.P. (2001). The triphasic nature of Leydig cell development in humans, and comments on nomenclature. J Endocrinol 168, 213–216.
Punab, M., Poolamets, O., Paju, P., Vihljajev, V., Pomm, K., Ladva, R., Korrovits, P., and Laan, M. (2016). Causes of male infertility: a 9-year prospective monocentre study on 1737 patients with reduced total sperm counts. Hum Reprod 21.
Puttabyatappa, M., Cardoso, R.C., and Padmanabhan, V. (2016). Effect of maternal PCOS and PCOS-like phenotype on the offspring’s health. Mol Cell Endocrinol 435, 29–39.
Qin, L., Huang, C.C., Yan, X.M., Wang, Y., Li, Z.Y., and Wei, X.C. (2019). Long non-coding RNA H19 is associated with polycystic ovary syndrome in Chinese women: a preliminary study. Endocr J 66, 587–595.
Qu, F., Wang, F.F., Yin, R., Ding, G.L., El-Prince, M., Gao, Q., Shi, B.W., Pan, H.H., Huang, Y.T., Jin, M., et al. (2012). A molecular mechanism underlying ovarian dysfunction of polycystic ovary syndrome: hyperandrogenism induces epigenetic alterations in the granulosa cells. J Mol Med 90, 911–923.
Quan, H.M., Fan, H.Y., Meng, X.Q., Huo, L.J., Chen, D.Y., Schatten, H., Yang, P.M., and Sun, Q.Y. (2003). Effects of PKC activation on the meiotic maturation, fertilization and early embryonic development of mouse oocytes. Zygote 11, 329–337.
Raassen, T.J.I.P., Ngongo, C.J., and Mahendeka, M.M. (2018). Diagnosis and management of 365 ureteric injuries following obstetric and gynecologic surgery in resource-limited settings. Int Urogynecol J 29, 1303–1309.
Ramasamy, R., Bakırcıoğlu, M.E., Cengiz, C., Karaca, E., Scovell, J., Jhangiani, S.N., Akdemir, Z.C., Bainbridge, M., Yu, Y., Huff, C., et al. (2015). Whole-exome sequencing identifies novel homozygous mutation in NPAS2 in family with nonobstructive azoospermia. Fertil Steril 104, 286–291.
Ran, F.A., Hsu, P.D., Lin, C.Y., Gootenberg, J.S., Konermann, S., Trevino, A.E., Scott, D.A., Inoue, A., Matoba, S., Zhang, Y., et al. (2013). Double nicking by RNA-guided CRISPR Cas9 for enhanced genome editing specificity. Cell 154, 1380–1389.
Ranjbaran, A., Nejabati, H.R., Ghasemnejad, T., Latifi, Z., Hamdi, K., Hajipour, H., Raffel, N., Bahrami-Asl, Z., Hakimi, P., Mihanfar, A., et al. (2019). Follicular fluid levels of adrenomedullin 2, vascular endothelial growth factor and its soluble receptors are associated with ovarian response during ART cycles. Geburtshilfe Frauenheilkd 79, 86–93.
Rao, S.S.P., Huntley, M.H., Durand, N.C., Stamenova, E.K., Bochkov, I.D., Robinson, J.T., Sanborn, A.L., Machol, I., Omer, A.D., Lander, E.S., et al. (2014). A 3D map of the human genome at kilobase resolution reveals principles of chromatin looping. Cell 159, 1665–1680.
Rathke, C., Baarends, W.M., Awe, S., and Renkawitz-Pohl, R. (2014). Chromatin dynamics during spermiogenesis. Biochim Biophys Acta Gene Regul Mech 1839, 155–168.
Rees, H.A., and Liu, D.R. (2018). Base editing: precision chemistry on the genome and transcriptome of living cells. Nat Rev Genet 19, 770–788.
Reis, A., Chang, H.Y., Levasseur, M., and Jones, K.T. (2006). APCcdh1 activity in mouse oocytes prevents entry into the first meiotic division. Nat Cell Biol 8, 539–540.
Remy, S., Tesson, L., Ménoret, S., Usal, C., Scharenberg, A.M., and Anegon, I. (2010). Zinc-finger nucleases: a powerful tool for genetic engineering of animals. Transgenic Res 19, 363–371.
Richter, O.N., Dorn, C., Rösing, B., Flaskamp, C., and Ulrich, U. (2005). Tumor necrosis factor alpha secretion by peritoneal macrophages in patients with endometriosis. Arch Gynecol Obstet 271, 143–147.
Rier, S.E., Martin, D.C., Bowman, R.E., Dmowski, W.P., and Becker, J.L. (1993). Endometriosis in rhesus monkeys (Macaca mulatta) following chronic exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin. Fund Appl Toxicol 21, 433–441.
Riera-Escamilla, A., Enguita-Marruedo, A., Moreno-Mendoza, D., Chianese, C., Sleddens-Linkels, E., Contini, E., Benelli, M., Natali, A., Colpi, G.M., Ruiz-Castañé, E., et al. (2019). Sequencing of a ‘mouse azoospermia’ gene panel in azoospermic men: identification of RNF212 and STAG3 mutations as novel genetic causes of meiotic arrest. Hum Reprod 34, 978–988.
Riggs, E.R., Ledbetter, D.H., and Martin, C.L. (2014). Genomic variation: lessons learned from whole-genome CNV analysis. Curr Genet Med Rep 2, 146–150.
Rodgers, R.J., and Irving-Rodgers, H.F. (2010). Formation of the ovarian follicular antrum and follicular fluid. Biol Reprod 82, 1021–1029.
Rodman, T.C., Pruslin, F.H., Hoffmann, H.P., and Allfrey, V.G. (1981). Turnover of basic chromosomal proteins in fertilized eggs: a cytoimmunochemical study of events in vivo. J Cell Biol 90, 351–361.
Ropke, A., Tewes, A.C., Gromoll, J., Kliesch, S., Wieacker, P., and Tüttelmann, F. (2013). Comprehensive sequence analysis of the NR5A1 gene encoding steroidogenic factor 1 in a large group of infertile males. Eur J Hum Genet 21, 1012–1015.
Saayman, S., Ali, S.A., Morris, K.V., and Weinberg, M.S. (2015). The therapeutic application of CRISPR/Cas9 technologies for HIV. Expert Opin Biol Ther 15, 819–830.
Sadri-Ardekani, H., Mizrak, S.C., van Daalen, S.K.M., Korver, C.M., Roepers-Gajadien, H.L., Koruji, M., Hovingh, S., de Reijke, T.M., de la Rosette, J.J.M.C.H., van der Veen, F., et al. (2009). Propagation of human spermatogonial stem cells in vitro. JAMA 302, 2127–2134.
Sagvekar, P., Kumar, P., Mangoli, V., Desai, S., and Mukherjee, S. (2019). DNA methylome profiling of granulosa cells reveals altered methylation in genes regulating vital ovarian functions in polycystic ovary syndrome. Clin Epigenet 11, 61.
Sagvekar, P., Mangoli, V., Desai, S., Patil, A., and Mukherjee, S. (2017). LINE1 CpG-DNA hypomethylation in granulosa cells and blood leukocytes is associated with PCOS and related traits. J Clin Endocrinol Metab 102, 1396–1405.
Saitou, M., and Miyauchi, H. (2016). Gametogenesis from pluripotent stem cells. Cell Stem Cell 18, 721–735.
Sakuma, T., and Yamamoto, T. (2017). Current Overview of TALEN Construction Systems. Methods Mol Biol 1630, 25–36.
Salehi Jahromi, M., Hill, J.W., Ramezani Tehrani, F., and Zadeh-Vakili, A. (2018). Hypomethylation of specific CpG sites in the promoter region of steroidogeneic genes (GATA6 and StAR) in prenatally androgenized rats. Life Sci 207, 105–109.
Salem, M.S., Alkaysi, H.N., Gharaibeh, A.M., Gharaibeh, N.M., and Badwant, A.A. (1994). Bioequivalence of two oral dosage forms prepared from different polymorphic modifications of tenoxicam. J Clin Pharm Ther 19, 203–207.
Sang, Q., Zhang, Z., Shi, J., Sun, X., Li, B., Yan, Z., Xue, S., Ai, A., Lyu, Q., Li, W., et al. (2019). A pannexin 1 channelopathy causes human oocyte death. Sci Transl Med 11, eaav8731.
Santonocito, M., Vento, M., Guglielmino, M.R., Battaglia, R., Wahlgren, J., Ragusa, M., Barbagallo, D., Borzì, P., Rizzari, S., Maugeri, M., et al. (2014). Molecular characterization of exosomes and their microRNA cargo in human follicular fluid: bioinformatic analysis reveals that exosomal microRNAs control pathways involved in follicular maturation. Fertil Steril 102, 1751–1761.e1.
Sasaki, K., Yokobayashi, S., Nakamura, T., Okamoto, I., Yabuta, Y., Kurimoto, K., Ohta, H., Moritoki, Y., Iwatani, C., Tsuchiya, H., et al. (2015). Robust in vitro induction of human germ cell fate from pluripotent stem cells. Cell Stem Cell 17, 178–194.
Schiroli, G., Conti, A., Ferrari, S., Della Volpe, L., Jacob, A., Albano, L., Beretta, S., Calabria, A., Vavassori, V., Gasparini, P., et al. (2019). Precise gene editing preserves hematopoietic stem cell function following transient p53-mediated DNA damage response. Cell Stem Cell 24, 551–565.e8.
Schmidt, A., Rauh, N.R., Nigg, E.A., and Mayer, T.U. (2006). Cytostatic factor: an activity that puts the cell cycle on hold. J Cell Sci 119, 1213–1218.
Scialdone, A., Tanaka, Y., Jawaid, W., Moignard, V., Wilson, N.K., Macaulay, I.C., Marioni, J.C., and Göttgens, B. (2016). Resolving early mesoderm diversification through single-cell expression profiling. Nature 535, 289–293.
Seisenberger, S., Andrews, S., Krueger, F., Arand, J., Walter, J., Santos, F., Popp, C., Thienpont, B., Dean, W., and Reik, W. (2012). The dynamics of genome-wide DNA methylation reprogramming in mouse primordial germ cells. Mol Cell 48, 849–862.
Shah, S., Lubeck, E., Zhou, W., and Cai, L. (2016). In situ transcription profiling of single cells reveals spatial organization of cells in the mouse hippocampus. Neuron 92, 342–357.
Sharma, A., Tiwari, M., Gupta, A., Pandey, A.N., Yadav, P.K., and Chaube, S.K. (2018). Journey of oocyte from metaphase-I to metaphase-II stage in mammals. J Cell Physiol 233, 5530–5536.
Sharpe-Timms, K.L., Zimmer, R.L., Ricke, E.A., Piva, M., and Horowitz, G.M. (2002). Endometriotic haptoglobin binds to peritoneal macrophages and alters their function in women with endometriosis. Fertil Steril 78, 810–819.
Shen, H.R., Qiu, L.H., Zhang, Z.Q., Qin, Y.Y., Cao, C., and Di, W. (2013). Genome-wide methylated DNA immunoprecipitation analysis of patients with polycystic ovary syndrome. PLoS ONE 8, e64801.
Shi, Y., Zhao, H., Shi, Y., Cao, Y., Yang, D., Li, Z., Zhang, B., Liang, X., Li, T., Chen, J., et al. (2012). Genome-wide association study identifies eight new risk loci for polycystic ovary syndrome. Nat Genet 44, 1020–1025.
Shirane, K., Toh, H., Kobayashi, H., Miura, F., Chiba, H., Ito, T., Kono, T., and Sasaki, H. (2013). Mouse oocyte methylomes at base resolution reveal genome-wide accumulation of non-CpG methylation and role of DNA methyltransferases. PLoS Genet 9, e1003439.
Shoji, S., Yoshida, N., Amanai, M., Ohgishi, M., Fukui, T., Fujimoto, S., Nakano, Y., Kajikawa, E., and Perry, A.C.F. (2006). Mammalian Emi2 mediates cytostatic arrest and transduces the signal for meiotic exit via Cdc20. EMBO J 25, 834–845.
Sikora, J., Mielczarek-Palacz, A., and Kondera-Anasz, Z. (2011). Role of natural killer cell activity in the pathogenesis of endometriosis. Curr Med Chem 18, 200–208.
Simoni, M., Tüttelmann, F., Gromoll, J., and Nieschlag, E. (2008). Clinical consequences of microdeletions of the Y chromosome: the extended Münster experience. Reprod Biomed Online 16, 289–303.
Sinaii, N. (2002). High rates of autoimmune and endocrine disorders, fibromyalgia, chronic fatigue syndrome and atopic diseases among women with endometriosis: a survey analysis. Hum Reprod 17, 2715–2724.
Singh, V.P., Yueh, W.T., Gerton, J.L., and Duncan, F.E. (2019). Oocyte-specific deletion of Hdac8 in mice reveals stage-specific effects on fertility. Reproduction 157, 305–316.
Smallwood, S.A., Tomizawa, S.I., Krueger, F., Ruf, N., Carli, N., Segonds-Pichon, A., Sato, S., Hata, K., Andrews, S.R., and Kelsey, G. (2011). Dynamic CpG island methylation landscape in oocytes and preimplantation embryos. Nat Genet 43, 811–814.
Smargon, A.A., Cox, D.B.T., Pyzocha, N.K., Zheng, K., Slaymaker, I.M., Gootenberg, J.S., Abudayyeh, O.A., Essletzbichler, P., Shmakov, S., Makarova, K.S., et al. (2017). Cas13b is a type VI-B CRISPR-associated RNA-guided RNase differentially regulated by accessory proteins Csx27 and Csx28. Mol Cell 65, 618–630.e7.
Smith, Z.D., Chan, M.M., Humm, K.C., Karnik, R., Mekhoubad, S., Regev, A., Eggan, K., and Meissner, A. (2014). DNA methylation dynamics of the human preimplantation embryo. Nature 511, 611–615.
Smith, Z.D., and Meissner, A. (2013). DNA methylation: roles in mammalian development. Nat Rev Genet 14, 204–220.
Sohni, A., Tan, K., Song, H.W., Burow, D., de Rooij, D.G., Laurent, L., Hsieh, T.C., Rabah, R., Hammoud, S.S., Vicini, E., et al. (2019). The Neonatal and Adult Human Testis Defined at the Single-Cell Level. Cell Rep 26, 1501–1517.e4.
Sorensen, A.E., Udesen, P.B., Wissing, M.L., Englund, A.L.M., and Dalgaard, L.T. (2016a). MicroRNAs related to androgen metabolism and polycystic ovary syndrome. Chem Biol Interact 259, 8–16.
Sorensen, A.E., Wissing, M.L., Englund, A.L.M., and Dalgaard, L.T. (2016b). MicroRNA species in follicular fluid associating with polycystic ovary syndrome and related intermediary phenotypes. J Clin Endocrinol Metab 101, 1579–1589.
Stahl, P.L., Salmén, F., Vickovic, S., Lundmark, A., Navarro, J.F., Magnusson, J., Giacomello, S., Asp, M., Westholm, J.O., Huss, M., et al. (2016). Visualization and analysis of gene expression in tissue sections by spatial transcriptomics. Science 353, 78–82.
Stewart, K.R., Veselovska, L., and Kelsey, G. (2016). Establishment and functions of DNA methylation in the germline. Epigenomics 8, 1399–1413.
Stewart, K.R., Veselovska, L., Kim, J., Huang, J., Saadeh, H., Tomizawa, S., Smallwood, S.A., Chen, T., and Kelsey, G. (2015). Dynamic changes in histone modifications precede de novo DNA methylation in oocytes. Genes Dev 29, 2449–2462.
Stouffs, K., Vandermaelen, D., Massart, A., Menten, B., Vergult, S., Tournaye, H., and Lissens, W. (2012). Array comparative genomic hybridization in male infertility. Hum Reprod 27, 921–929.
Su, T., Stanley, G., Sinha, R., D’Amato, G., Das, S., Rhee, S., Chang, A.H., Poduri, A., Raftrey, B., Dinh, T.T., et al. (2018). Single-cell analysis of early progenitor cells that build coronary arteries. Nature 559, 356–362.
Suen, J.L., Chang, Y., Chiu, P.R., Hsieh, T.H., Hsi, E., Chen, Y.C., Chen, Y. F., and Tsai, E.M. (2014). Serum level of IL-10 is increased in patients with endometriosis, and IL-10 promotes the growth of lesions in a murine model. Am J Pathol 184, 464–471.
Suginami, H. (1991). A reappraisal of the coelomic metaplasia theory by reviewing, endometriosis occurring in unusual sites and instances. Am J Obstet Gynecol 165, 214–218.
Sung, P., and Klein, H. (2006). Mechanism of homologous recombination: mediators and helicases take on regulatory functions. Nat Rev Mol Cell Biol 7, 739–750.
Svechnikov, K., Landreh, L., Weisser, J., Izzo, G., Colón, E., Svechnikova, I., and Söder, O. (2010). Origin, development and regulation of human Leydig cells. Horm Res Paediatr 73, 93–101.
Svoboda, P. (2017). Long and small noncoding RNAs during oocyte-to-embryo transition in mammals. Biochem Soc Trans 45, 1117–1124.
Tadros, W., and Lipshitz, H.D. (2009). The maternal-to-zygotic transition: a play in two acts. Development 136, 3033–3042.
Tang, L., Zeng, Y., Du, H., Gong, M., Peng, J., Zhang, B., Lei, M., Zhao, F., Wang, W., Li, X., et al. (2017). CRISPR/Cas9-mediated gene editing in human zygotes using Cas9 protein. Mol Genet Genomics 292, 525–533.
Tang, W.W.C., Dietmann, S., Irie, N., Leitch, H.G., Floros, V.I., Bradshaw, C.R., Hackett, J.A., Chinnery, P.F., and Surani, M.A. (2015). A unique gene regulatory network resets the human germline epigenome for development. Cell 161, 1453–1467.
Tang, W.W.C., Kobayashi, T., Irie, N., Dietmann, S., and Surani, M.A. (2016). Specification and epigenetic programming of the human germ line. Nat Rev Genet 17, 585–600.
Tasan, I., and Zhao, H. (2017). Targeting specificity of the CRISPR/Cas9 system. ACS Synth Biol 6, 1609–1613.
Tee, M.K., Speek, M., Legeza, B., Modi, B., Teves, M.E., McAllister, J.M., Strauss Iii, J.F., and Miller, W.L. (2016). Alternative splicing of DENND1A, a PCOS candidate gene, generates variant 2. Mol Cell Endocrinol 434, 25–35.
Tenenbaum-Rakover, Y., Weinberg-Shukron, A., Renbaum, P., Lobel, O., Eideh, H., Gulsuner, S., Dahary, D., Abu-Rayyan, A., Kanaan, M., Levy-Lahad, E., et al. (2015). Minichromosome maintenance complex component 8 (MCM8) gene mutations result in primary gonadal failure. J Med Genet 52, 391–399.
Terret, M.E., Lefebvre, C., Djiane, A., Rassinier, P., Moreau, J., Maro, B., and Verlhac, M.H. (2003). DOC1R: a MAP kinase substrate that control microtubule organization of metaphase II mouse oocytes. Development 130, 5169–5177.
Thornton, B.R., and Toczyski, D.P. (2006). Precise destruction: an emerging picture of the APC. Genes Dev 20, 3069–3078.
Torres-Padilla, M.E., Bannister, A.J., Hurd, P.J., Kouzarides, T., and Zernicka-Goetz, M. (2006). Dynamic distribution of the replacement histone variant H3.3 in the mouse oocyte and preimplantation embryos. Int J Dev Biol 50, 455–461.
Tripathi, A., Kumar, K.V.P., and Chaube, S.K. (2010). Meiotic cell cycle arrest in mammalian oocytes. J Cell Physiol 67.
Tsai, S.Q., and Joung, J.K. (2016). Defining and improving the genome-wide specificities of CRISPR-Cas9 nucleases. Nat Rev Genet 17, 300–312.
Tucci, S., Futterweit, W., Concepcion, E.S., Greenberg, D.A., Villanueva, R., Davies, T.F., and Tomer, Y. (2001). Evidence for association of polycystic ovary syndrome in caucasian women with a marker at the insulin receptor gene locus. J Clin Endocrinol Metab 86, 446–449.
Tuttelmann, F., Simoni, M., Kliesch, S., Ledig, S., Dworniczak, B., Wieacker, P., and Röpke, A. (2011a). Copy number variants in patients with severe oligozoospermia and Sertoli-cell-only syndrome. PLoS ONE 6, e19426.
Tuttelmann, F., Werny, F., Cooper, T.G., Kliesch, S., Simoni, M., and Nieschlag, E. (2011b). Clinical experience with azoospermia: aetiology and chances for spermatozoa detection upon biopsy. Int J Androl 34, 291–298.
Urbanek, M., Woodroffe, A., Ewens, K.G., Diamanti-Kandarakis, E., Legro, R.S., Strauss Iii, J.F., Dunaif, A., and Spielman, R.S. (2005). Candidate gene region for polycystic ovary syndrome on chromosome 19p13.2. J Clin Endocrinol Metab 90, 6623–6629.
Van Handel, B., Montel-Hagen, A., Sasidharan, R., Nakano, H., Ferrari, R., Boogerd, C.J., Schredelseker, J., Wang, Y., Hunter, S., Org, T., et al. (2012). Scl represses cardiomyogenesis in prospective hemogenic endothelium and endocardium. Cell 150, 590–605.
Vassena, R., Boué, S., González-Roca, E., Aran, B., Auer, H., Veiga, A., and Izpisua Belmonte, J.C. (2011). Waves of early transcriptional activation and pluripotency program initiation during human preimplantation development. Development 138, 3699–3709.
Vercellini, P., Viganò, P., Somigliana, E., and Fedele, L. (2014). Endometriosis: pathogenesis and treatment. Nat Rev Endocrinol 10, 261–275.
Villuendas, G., Escobar-Morreale, H.F., Tosi, F., Sancho, J., Moghetti, P., and San Millán, J.L. (2003). Association between the D19S884 marker at the insulin receptor gene locus and polycystic ovary syndrome. Fertil Steril 79, 219–220.
Vink, J.M., Sadrzadeh, S., Lambalk, C.B., and Boomsma, D.I. (2006). Heritability of polycystic ovary syndrome in a Dutch twin-family study. J Clin Endocrinol Metab 91, 2100–2104.
Viveiros, M.M., O’Brien, M., and Eppig, J.J. (2004). Protein kinase C activity regulates the onset of anaphase I in mouse oocytes. Biol Reprod 71, 1525–1532.
Wagner, I.V., Yango, P., Svechnikov, K., Tran, N.D., and Söder, O. (2019). Adipocytokines may delay pubertal maturation of human Sertoli cells. Reprod Fertil Dev 31, 1395.
Wang, Z.B., Ou, X.H., Tong, J.S., Li, S., Wei, L., Ouyang, Y.C., Hou, Y., Schatten, H., and Sun, Q.Y. (2010). The SUMO pathway functions in mouse oocyte maturation. Cell Cycle 9, 2640–2646.
Wang, C., Liu, X., Gao, Y., Yang, L., Li, C., Liu, W., Chen, C., Kou, X., Zhao, Y., Chen, J., et al. (2018a). Reprogramming of H3K9me3-dependent heterochromatin during mammalian embryo development. Nat Cell Biol 20, 620–631.
Wang, F., Pan, J., Liu, Y., Meng, Q., Lv, P., Qu, F., Ding, G.L., Klausen, C., Leung, P.C.K., Chan, H.C., et al. (2015). Alternative splicing of the androgen receptor in polycystic ovary syndrome. Proc Natl Acad Sci USA 112, 4743–4748.
Wang, L., Zhang, J., Duan, J., Gao, X., Zhu, W., Lu, X., Yang, L., Zhang, J., Li, G., Ci, W., et al. (2014a). Programming and inheritance of parental DNA methylomes in mammals. Cell 157, 979–991.
Wang, L.P., Peng, X.Y., Lv, X.Q., Liu, L., Li, X.L., He, X., Lv, F., Pan, Y., Wang, L., Liu, K.F., et al. (2019a). High throughput circRNAs sequencing profile of follicle fluid exosomes of polycystic ovary syndrome patients. J Cell Physiol 234, 15537–15547.
Wang, M., Liu, X., Chang, G., Chen, Y., An, G., Yan, L., Gao, S., Xu, Y., Cui, Y., Dong, J., et al. (2018b). Single-cell RNA sequencing analysis reveals sequential cell fate transition during human spermatogenesis. Cell Stem Cell 23, 599–614.e4.
Wang, J., Fan, H.C., Behr, B., and Quake, S.R. (2012). Genome-wide single-cell analysis of recombination activity and de novo mutation rates in human sperm. Cell 150, 402–412.
Wang, P., Zhao, H., Li, T., Zhang, W., Wu, K., Li, M., Bian, Y., Liu, H., Ning, Y., Li, G., et al. (2014b). Hypomethylation of the LH/choriogonadotropin receptor promoter region is a potential mechanism underlying susceptibility to polycystic ovary syndrome. Endocrinology 155, 1445–1452.
Wang, R., Goodarzi, M.O., Xiong, T., Wang, D., Azziz, R., and Zhang, H. (2012). Negative association between androgen receptor gene CAG repeat polymorphism and polycystic ovary syndrome? A systematic review and meta-analysis. MHR Basic Sci Reprod Med 18, 498–509.
Wang, T., Liu, Y., Lv, M., Xing, Q., Zhang, Z., He, X., Xu, Y., Wei, Z., and Cao, Y. (2019b). miR-323-3p regulates the steroidogenesis and cell apoptosis in polycystic ovary syndrome (PCOS) by targeting IGF-1. Gene 683, 87–100.
Wang, X., Allen, W.E., Wright, M.A., Sylwestrak, E.L., Samusik, N., Vesuna, S., Evans, K., Liu, C., Ramakrishnan, C., Liu, J., et al. (2018c). Three-dimensional intact-tissue sequencing of single-cell transcriptional states. Science 361, eaat5691.
Wang, X.X., Wei, J.Z., Jiao, J., Jiang, S.Y., Yu, D.H., and Li, D. (2014c). Genome-wide DNA methylation and gene expression patterns provide insight into polycystic ovary syndrome development. Oncotarget 5.
Wang, Y., Wu, X.K., Cao, Y., Yi, L., and Chen, J. (2006). A microsatellite polymorphism (tttta)n in the promoter of the CYP11a gene in Chinese women with polycystic ovary syndrome. Fertil Steril 86, 223–226.
Wells, N.J., Watanabe, N., Tokusumi, T., Jiang, W., Verdecia, M.A., and Hunter, T. (1999). The C-terminal domain of the Cdc2 inhibitory kinase Myt1 interacts with Cdc2 complexes and is required for inhibition of G (2)/M progression. J Cell Sci 112, 3361–3371.
Wen, L., and Tang, F. (2016). Single-cell sequencing in stem cell biology. Genome Biol 17, 71.
Wu, J., Huang, B., Chen, H., Yin, Q., Liu, Y., Xiang, Y., Zhang, B., Liu, B., Wang, Q., Xia, W., et al. (2016). The landscape of accessible chromatin in mammalian preimplantation embryos. Nature 534, 652–657.
Wu, J., Xu, J., Liu, B., Yao, G., Wang, P., Lin, Z., Huang, B., Wang, X., Li, T., Shi, S., et al. (2018). Chromatin analysis in human early development reveals epigenetic transition during ZGA. Nature 557, 256–260.
Wu, X., Scott, D.A., Kriz, A.J., Chiu, A.C., Hsu, P.D., Dadon, D.B., Cheng, A.W., Trevino, A.E., Konermann, S., Chen, S., et al. (2014). Genome-wide binding of the CRISPR endonuclease Cas9 in mammalian cells. Nat Biotechnol 32, 670–676.
Xiang, J., Wang, W., Qian, C., Xue, J., Wang, T., Li, H., and Li, H. (2018). Human oocyte maturation arrest caused by a novel missense mutation in TUBB8. J Int Med Res 46, 3759–3764.
Xie, G., Xu, P., Che, Y., Xia, Y., Cao, Y., Wang, W., Qiao, D., Wu, X., Yi, L., Gao, Q., et al. (2013). Microsatellite polymorphism in the fibrillin 3 gene and susceptibility to PCOS: a case-control study and meta-analysis. Reprod Biomed Online 26, 168–174.
Xu, J., Bao, X., Peng, Z., Wang, L., Du, L., Niu, W., and Sun, Y. (2016). Comprehensive analysis of genome-wide DNA methylation across human polycystic ovary syndrome ovary granulosa cell. Oncotarget 7.
Xu, K., Chen, X., Yang, H., Xu, Y., He, Y., Wang, C., Huang, H., Liu, B., Liu, W., Li, J., et al. (2017a). Maternal Sall4 is indispensable for epigenetic maturation of mouse oocytes. J Biol Chem 292, 1798–1807.
Xu, L., Yang, H., Gao, Y., Chen, Z., Xie, L., Liu, Y., Liu, Y., Wang, X., Li, H., Lai, W., et al. (2017b). CRISPR/Cas9-mediated CCR5 ablation in human hematopoietic stem/progenitor cells confers HIV-1 resistance in vivo. Mol Ther 25, 1782–1789.
Xu, N., Azziz, R., and Goodarzi, M.O. (2010). Epigenetics in polycystic ovary syndrome: a pilot study of global DNA methylation. Fertil Steril 94, 781–783.e1.
Xu, N., Chua, A.K., Jiang, H., Liu, N.A., and Goodarzi, M.O. (2014). Early embryonic androgen exposure induces transgenerational epigenetic and metabolic changes. Mol Endocrinol 28, 1329–1336.
Xu, N., Kwon, S., Abbott, D.H., Geller, D.H., Dumesic, D.A., Azziz, R., Guo, X., and Goodarzi, M.O. (2011). Epigenetic mechanism underlying the development of polycystic ovary syndrome (PCOS)-like phenotypes in prenatally androgenized rhesus monkeys. PLoS ONE 6, e27286.
Xue, Z., Huang, K., Cai, C., Cai, L., Jiang, C., Feng, Y., Liu, Z., Zeng, Q., Cheng, L., Sun, Y.E., et al. (2013). Genetic programs in human and mouse early embryos revealed by single-cell RNA sequencing. Nature 500, 593–597.
Yamanaka, Y., Lanner, F., and Rossant, J. (2010). FGF signal-dependent segregation of primitive endoderm and epiblast in the mouse blastocyst. Development 137, 715–724.
Yan, L., Yang, M., Guo, H., Yang, L., Wu, J., Li, R., Liu, P., Lian, Y., Zheng, X., Yan, J., et al. (2013). Single-cell RNA-Seq profiling of human preimplantation embryos and embryonic stem cells. Nat Struct Mol Biol 20, 1131–1139.
Yan, W.X., Chong, S., Zhang, H., Makarova, K.S., Koonin, E.V., Cheng, D. R., and Scott, D.A. (2018). Cas13d is a compact RNA-targeting type VI CRISPR effector positively modulated by a WYL-domain-containing accessory protein. Mol Cell 70, 327–339.e5.
Yang, F., Silber, S., Leu, N.A., Oates, R.D., Marszalek, J.D., Skaletsky, H., Brown, L.G., Rozen, S., Page, D.C., and Wang, P.J. (2015). TEX 11 is mutated in infertile men with azoospermia and regulates genome-wide recombination rates in mouse. EMBO Mol Med 7, 1198–1210.
Yang, J., and Huang, F. (2014). Stem cell and endometriosis: new knowledge may be producing novel therapies. Int J Clin Exp Med 7, 3853–3858.
Yang, Q., and Ferrell, J.E. (2013). The Cdk1-APC/C cell cycle oscillator circuit functions as a time-delayed, ultrasensitive switch. Nat Cell Biol 15, 519–525.
Yang, R., Chen, J., Wang, L., and Deng, A. (2018). LncRNA BANCR participates in polycystic ovary syndrome by promoting cell apoptosis. Mol Med Report.
Yao, L., Li, M., Hu, J., Wang, W., and Gao, M. (2018). MiRNA-335-5p negatively regulates granulosa cell proliferation via SGK3 in PCOS. Reproduction 439–449.
Yatsenko, A.N., Georgiadis, A.P., Röpke, A., Berman, A.J., Jaffe, T., Olszewska, M., Westernströer, B., Sanfilippo, J., Kurpisz, M., Rajkovic, A., et al. (2015). X-linked TEX11 mutations, meiotic arrest, and azoospermia in infertile men. N Engl J Med 372, 2097–2107.
Yatsenko, A.N., Roy, A., Chen, R., Ma, L., Murthy, L.J., Yan, W., Lamb, D. J., and Matzuk, M.M. (2006). Non-invasive genetic diagnosis of male infertility using spermatozoal RNA: KLHL10 mutations in oligozoospermic patients impair homodimerization. Hum Mol Genet 15, 3411–3419.
Yi, Z.Y., Liang, Q.X., Meng, T.G., Li, J., Dong, M.Z., Hou, Y., Ouyang, Y.C., Zhang, C.H., Schatten, H., Sun, Q.Y., et al. (2019). PKCβ1 regulates meiotic cell cycle in mouse oocyte. Cell Cycle 18, 395–412.
Yoshimura, A., Wakabayashi, Y., and Mori, T. (2010). Cellular and molecular basis for the regulation of inflammation by TGF-beta. J Biochem 147, 781–792.
Yu, B., Dong, X., Gravina, S., Kartal, Ö., Schimmel, T., Cohen, J., Tortoriello, D., Zody, R., Hawkins, R.D., and Vijg, J. (2017). Genome-wide, single-cell DNA methylomics reveals increased non-CpG methylation during human oocyte maturation. Stem Cell Rep 9, 397–407.
Yu, J., Wang, Y., Zhou, W.H., Wang, L., He, Y.Y., and Li, D.J. (2008). Combination of estrogen and dioxin is involved in the pathogenesis of endometriosis by promoting chemokine secretion and invasion of endometrial stromal cells. Hum Reprod 23, 1614–1626.
Yu, M., and Ren, B. (2017). The three-dimensional organization of mammalian genomes. Annu Rev Cell Dev Biol 33, 265–289.
Yu, Y.Y., Sun, C.X., Liu, Y.K., Li, Y., Wang, L., and Zhang, W. (2013). Promoter methylation of CYP19A1 gene in Chinese polycystic ovary syndrome patients. Gynecol Obstet Invest 76, 209–213.
Yu, Y.Y., Sun, C.X., Liu, Y.K., Li, Y., Wang, L., and Zhang, W. (2015). Genome-wide screen of ovary-specific DNA methylation in polycystic ovary syndrome. Fertil Steril 104, 145–153.e6.
Zare-Abdollahi, D., Safari, S., Mirfakhraie, R., Movafagh, A., Bastami, M., Azimzadeh, P., Salsabili, N., Ebrahimizadeh, W., Salami, S., and Omrani, M.D. (2015). Mutational screening of the NR5A1 in azoospermia. Andrologia 47, 395–401.
Zhang, B., Zheng, H., Huang, B., Li, W., Xiang, Y., Peng, X., Ming, J., Wu, X., Zhang, Y., Xu, Q., et al. (2016). Allelic reprogramming of the histone modification H3K4me3 in early mammalian development. Nature 537, 553–557.
Zhang, C., Liu, J., Lai, M., Li, J., Zhan, J., Wen, Q., and Ma, H. (2019a). Circular RNA expression profiling of granulosa cells in women of reproductive age with polycystic ovary syndrome. Arch Gynecol Obstet 300, 431–440.
Zhang, K., Lu, Y., Jiang, C., Liu, W., Shu, J., Chen, X., Shi, Y., Wang, E., Wang, L., Hu, Q., et al. (2017). HDAC8 functions in spindle assembly during mouse oocyte meiosis. Oncotarget 8.
Zhang, M., Su, Y.Q., Sugiura, K., Xia, G., and Eppig, J.J. (2010). Granulosa cell ligand NPPC and its receptor NPR2 maintain meiotic arrest in mouse oocytes. Science 330, 366–369.
Zhang, T., De Carolis, C., Man, G.C.W., and Wang, C.C. (2018a). The link between immunity, autoimmunity and endometriosis: a literature update. Autoimmun Rev 17, 945–955.
Zhang, Y., Wu, L.L., Wan, X., Wang, H.H., Li, X.H., Pan, Z.N., and Sun, S. C. (2019b). Loss of PKC mu function induces cytoskeletal defects in mouse oocyte meiosis. J Cell Physiol 215, jcp.28487.
Zhang, Y., Yan, Z., Qin, Q., Nisenblat, V., Chang, H.M., Yu, Y., Wang, T., Lu, C., Yang, M., Yang, S., et al. (2018b). Transcriptome landscape of human folliculogenesis reveals oocyte and granulosa cell interactions. Mol Cell 72, 1021–1034.e4.
Zhao, C., Liu, X., Shi, Z., Zhang, J., Zhang, J., Jia, X., and Ling, X. (2015). Role of serum miRNAs in the prediction of ovarian hyperstimulation syndrome in polycystic ovarian syndrome patients. Cell Physiol Biochem 35, 1086–1094.
Zhao, H., Xu, J., Zhang, H., Sun, J., Sun, Y., Wang, Z., Liu, J., Ding, Q., Lu, S., Shi, R., et al. (2012). A genome-wide association study reveals that variants within the HLA region are associated with risk for nonobstructive azoospermia. Am J Hum Genet 90, 900–906.
Zhao, J., Xu, J., Wang, W., Zhao, H., Liu, H., Liu, X., Liu, J., Sun, Y., Dunaif, A., Du, Y., et al. (2018). Long non-coding RNA LINC-01572:28 inhibits granulosa cell growth via a decrease in p27 (Kip1) degradation in patients with polycystic ovary syndrome. EBioMedicine 36, 526–538.
Zheng, H., Huang, B., Zhang, B., Xiang, Y., Du, Z., Xu, Q., Li, Y., Wang, Q., Ma, J., Peng, X., et al. (2016). Resetting epigenetic memory by reprogramming of histone modifications in mammals. Mol Cell 63, 1066–1079.
Zhong, Z., Li, F., Li, Y., Qin, S., Wen, C., Fu, Y., and Xiao, Q. (2018). Inhibition of microRNA-19b promotes ovarian granulosa cell proliferation by targeting IGF-1 in polycystic ovary syndrome. Mol Med Report.
Zhou, C., Zhang, M., Wei, Y., Sun, Y., Sun, Y., Pan, H., Yao, N., Zhong, W., Li, Y., Li, W., et al. (2017). Highly efficient base editing in human tripronuclear zygotes. Protein Cell 8, 772–775.
Zhou, Q., Wang, M., Yuan, Y., Wang, X., Fu, R., Wan, H., Xie, M., Liu, M., Guo, X., Zheng, Y., et al. (2016). Complete meiosis from embryonic stem cell-derived germ cells in vitro. Cell Stem Cell 18, 330–340.
Zhou, Z., Zheng, D., Wu, H., Li, R., Xu, S., Kang, Y., Cao, Y., Chen, X., Zhu, Y., Xu, S., et al. (2018). Epidemiology of infertility in China: a population-based study. BJOG 125, 432–441.
Ziller, M.J., Müller, F., Liao, J., Zhang, Y., Gu, H., Bock, C., Boyle, P., Epstein, C.B., Bernstein, B.E., Lengauer, T., et al. (2011). Genomic distribution and inter-sample variation of non-CpG methylation across human cell types. PLoS Genet 7, e1002389.
Zondervan, K.T., Becker, C.M., Koga, K., Missmer, S.A., Taylor, R.N., and Viganò, P. (2018). Endometriosis. Nat Rev Dis Primers 4, 9.
Zuo, E., Sun, Y., Wei, W., Yuan, T., Ying, W., Sun, H., Yuan, L., Steinmetz, L.M., Li, Y., and Yang, H. (2019). Cytosine base editor generates substantial off-target single-nucleotide variants in mouse embryos. Science 148, eaav9973.
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Compliance and ethics The author(s) declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Wen, L., Liu, Q., Xu, J. et al. Recent advances in mammalian reproductive biology. Sci. China Life Sci. 63, 18–58 (2020). https://doi.org/10.1007/s11427-019-1572-7
Received:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11427-019-1572-7