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Subcortical maternal complex (SCMC) expression during folliculogenesis is affected by oocyte donor age in sheep

  • Gamete Biology
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Journal of Assisted Reproduction and Genetics Aims and scope Submit manuscript

Abstract

Purpose

The age-associated decline in female fertility is largely ascribable to the decrease in oocyte quality. The subcortical maternal complex (SCMC) is a multiprotein complex essential for early embryogenesis and female fertility and functionally conserved across mammals. The present work evaluated expression dynamics of its components during folliculogenesis in relation to maternal age in sheep.

Methods

The expression of the SCMC components (KHDC3/FILIA, NLRP2, NLRP5/MATER, OOEP/FLOPED, PADI6, TLE6 and ZBED3) was analyzed by real-time PCR in pools of growing oocytes (GO) of different diameters (70–90 μm (S), 90–110 μm (M), or 110–130 μm (L)) derived from non-hormonally treated adult (Ad; age < 4 years), prepubertal (Pr; age 40 days), or aged ewes (age > 6 years).

Results

Specific expression patterns associated with donor age were observed during folliculogenesis for all genes, except ZBED3. In oocytes of adult donors, the synthesis of NLRP2, NLRP5, PADI6, and ZBED3 mRNAs was complete in S GO, while FILIA, TLE6, and OOEP were actively transcribed at this stage. Conversely, Pr GO showed active transcription of all mRNAs, except for ZBED3, during the entire window of oocyte growth. Notably, aged GO showed a completely inverse pattern, with a decrease of NLRP2, TLE6, FILIA, and PADI6 mRNA abundance during the latest stage of oocyte growth (L GO). Interestingly, MATER showed high expression variability, suggesting large inter-oocyte differences.

Conclusion

Our study describes the SCMC expression dynamics during sheep oogenesis and reports age-specific patterns that are likely involved in the age-related decline of oocyte quality.

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References

  1. Li L, Baibakov B, Dean J. A subcortical maternal complex essential for preimplantation mouse embryogenesis. Dev Cell. 2008;15:416–25.

    CAS  PubMed  PubMed Central  Google Scholar 

  2. Zhu K, Yan L, Zhang X, Lu X, Wang T, Yan J, et al. Identification of a human subcortical maternal complex. Mol Hum Reprod. 2015;21:320–9.

    CAS  PubMed  Google Scholar 

  3. Ohsugi M, Zheng P, Baibakov B, Li L, Dean J. Maternally derived FILIAMATER complex localizes asymmetrically in cleavage-stage mouse embryos. Development. 2008;135:259–69.

    CAS  PubMed  Google Scholar 

  4. Zheng P, Dean J. Oocyte-specific genes affect folliculogenesis, fertilization, and early development. Semin Reprod Med. 2007;25:243–51.

    CAS  PubMed  Google Scholar 

  5. Ledda S, Bebbere D, Ariu F, Pescatori M, Pau S, Zedda MT, et al. Unveiling mRNA changes during meiotic progression and pre-implantation development: help from large animal models. Curr Pharm Des. 2012;18:256–63.

    CAS  PubMed  Google Scholar 

  6. Dean J. Oocyte-specific genes regulate follicle formation, fertility and early mouse development. J Reprod Immunol. 2002;53:171–80.

    CAS  PubMed  Google Scholar 

  7. Zhang K, Smith GW. Maternal control of early embryogenesis in mammals. Reprod Fertil Dev. 2015;27:880–96.

    CAS  PubMed  PubMed Central  Google Scholar 

  8. Bebbere D, Ariu F, Bogliolo L, Masala L, Murrone O, Fattorini M, et al. Expression of maternally derived KHDC3, NLRP5, OOEP and TLE6 is associated with oocyte developmental competence in the ovine species. BMC Dev Biol. 2014;14:40.

    PubMed  PubMed Central  Google Scholar 

  9. Bebbere D, Masala L, Albertini DF, Ledda S. The subcortical maternal complex: multiple functions for one biological structure? J Assist Reprod Genet. 2016;33:1431–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  10. Yu XJ, Yi Z, Gao Z, Qin D, Zhai Y, Chen X, et al. The subcortical maternal complex controls symmetric division of mouse zygotes by regulating F-actin dynamics. Nat Commun. 2014;5:4887.

    CAS  PubMed  Google Scholar 

  11. Lu X, Gao Z, Qin D, Li L. A maternal functional module in the mammalian oocyte-to-embryo transition. Trends Mol Med. 2017;23:1014–23.

    PubMed  Google Scholar 

  12. Mahadevan S, Sathappan V, Utama B, Lorenzo I, Kaskar K, Van den Veyver IB. Maternally expressed NLRP2 links the subcortical maternal complex (SCMC) to fertility, embryogenesis and epigenetic reprogramming. Sci Rep. 2017;7:44667.

    CAS  PubMed  PubMed Central  Google Scholar 

  13. Tong ZB, Gold L, Pfeifer KE, Dorward H, Lee E, Bondy CA, et al. Mater, A maternal effect gene required for early embryonic development in mice. Nat Genet. 2000;26:267–8.

    CAS  PubMed  Google Scholar 

  14. Tashiro F, Kanai-Azuma M, Miyazaki S, Kato M, Tanaka T, Toyoda S, et al. Maternal-effect gene Ces5/Ooep/Moep19/Floped is essential for oocyte cytoplasmic lattice formation and embryonic development at the maternal-zygotic stage transition. Genes Cells. 2010;15:813–28.

    CAS  PubMed  Google Scholar 

  15. Zheng P, Dean J. Role of Filia, A maternal effect gene, in maintaining euploidy during cleavage-stage mouse embryogenesis. Proc Natl Acad Sci U S A. 2009;106:7473–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  16. Gao Z, Zhang X, Yu X, Qin D, Xiao Y, Yu Y, et al. Yi Z3, Li L. Zbed3 participates in the subcortical maternal complex and regulates the distribution of organelles. J Mol Cell Biol. 2018;10:74–88.

    CAS  PubMed  Google Scholar 

  17. Xu Y, Shi Y, Fu J, Yu M, Feng R, Sang Q, et al. Mutations in PADI6 cause female infertility characterized by early embryonic arrest. Am J Hum Genet. 2016;99:744–52.

    CAS  PubMed  PubMed Central  Google Scholar 

  18. Wang X, Song D, Mykytenko D, Kuang Y, Lv Q, Li B, et al. Novel mutations in genes encoding subcortical maternal complex proteins may cause human embryonic developmental arrest. Reprod BioMed Online. 2018;36:698–704.

    PubMed  Google Scholar 

  19. Lin J, Xu H, Chen B, Wang W, Wang L, Sun X, et al. Expanding the genetic and phenotypic spectrum of female infertility caused by TLE6 mutations. J Assist Reprod Genet. 2020;37:437–42.

    PubMed  PubMed Central  Google Scholar 

  20. Zheng W, Chen L, Dai J, Dai C, Guo J, Lu C, et al. New biallelic mutations in PADI6 cause recurrent preimplantation embryonic arrest characterized by direct cleavage. J Assist Reprod Genet. 2020;37:205–12.

    PubMed  Google Scholar 

  21. Krisher RL. Maternal age affects oocyte developmental potential at both ends of the age spectrum. Reprod Fertil Dev. 2018;31:1–9.

    PubMed  Google Scholar 

  22. Cimadomo D, Fabozzi G, Vaiarelli A, Ubaldi N, Ubaldi FM, Rienzi L. Impact of maternal age on oocyte and embryo competence. Front Endocrinol (Lausanne). 2018;9:327.

    Google Scholar 

  23. Ledda S, Bebbere D. Oocyte quality during reproductive ageing: are the chromosomal abnormalities the only problem? Hum Reprod. 2019;34(1):i23.

    Google Scholar 

  24. Hamatani T, Falco G, Carter MG, Akutsu H, Stagg CA, Sharov AA, et al. Age-associated alteration of gene expression patterns in mouse oocytes. Hum Mol Genet. 2004;13:2263–78.

    CAS  PubMed  Google Scholar 

  25. Lu YQ, He XC, Zheng P. Decrease in expression of maternal effect gene Mater is associated with maternal ageing in mice. Mol Hum Reprod. 2016;22:252–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  26. Bustin SA, Benes V, Garson JA, Hellemans J, Huggett J, Kubista M, et al. The MIQE guidelines: minimum information for publication of quantitative real-time PCR experiments. Clin Chem. 2009;55:611–22.

    CAS  PubMed  Google Scholar 

  27. Taylor SC, Nadeau K, Abbasi M, Lachance C, Nguyen M, Fenrich J. The ultimate qPCR experiment: producing publication quality, reproducible data the first time. Trends Biotechnol. 2019;37:761–74.

    CAS  PubMed  Google Scholar 

  28. Evsikov AV, Marín de Evsikova C. Gene expression during the oocyte-to embryo transition in mammals. Mol Reprod Dev. 2009;76:805–18.

    CAS  PubMed  PubMed Central  Google Scholar 

  29. Su YQ, Sugiura K, Woo Y, Wigglesworth K, Kamdar S, Affourtit J, et al. Selective degradation of transcripts during meiotic maturation of mouse oocytes. Dev Biol. 2007;302:104–17.

    CAS  PubMed  Google Scholar 

  30. McDaniel P, Wu X. Identification of oocyte-selective NLRP genes in rhesus macaque monkeys (Macaca mulatta). Mol Reprod Dev. 2009;76:151–9.

    CAS  PubMed  Google Scholar 

  31. Kuchmiy AA, D’Hont J, Hochepied T, Lamkanfi M. NLRP2 controls age-associated maternal fertility. J Exp Med. 2016;213:2851–60.

    CAS  PubMed  PubMed Central  Google Scholar 

  32. Chavanas S, Méchin MC, Takahara H, Kawada A, Nachat R, Serre G, et al. Comparative analysis of the mouse and human peptidylarginine deiminase gene clusters reveals highly conserved non-coding segments and a new human gene, PADI6. Gene. 2004;330:19–27.

    CAS  PubMed  Google Scholar 

  33. Fagerberg L, Hallström BM, Oksvold P, Kampf C, Djureinovic D, Odeberg J, et al. Analysis of the human tissue-specific expression by genome-wide integration of transcriptomics and antibody-based proteomics. Mol Cell Proteomics. 2014;13:397–406.

    CAS  PubMed  Google Scholar 

  34. Pierre A, Gautier M, Callebaut I, Bontoux M, Jeanpierre E, Pontarotti P, et al. Atypical structure and phylogenomic evolution of the new eutherian oocyte- and embryo-expressed KHDC1/DPPA5/ECAT1/OOEP gene family. Genomics. 2007;90:583–94.

    CAS  PubMed  Google Scholar 

  35. Khatir H, Lonergan P, Carolan C, Mermillod P. Prepubertal bovine oocyte: a negative model for studying oocyte developmental competence. Mol Reprod Dev. 1996;45:231–9.

    CAS  PubMed  Google Scholar 

  36. Nicholas FW. Genetic improvement through reproductive technology. Anim Reprod Sci. 1996;42:205–14.

    Google Scholar 

  37. Morton KM. Developmental capabilities of embryos produced in vitro from prepubertal lamb oocytes. Reprod Domest Anim. 2008;43:137–43.

    PubMed  Google Scholar 

  38. Armstrong DT, Holm P, Irvine B, Petersen BA, Stubbings RB, McLean D, et al. Pregnancies and live birth from in vitro fertilization of calf oocytes collected by laparoscopic follicular aspiration. Theriogenology. 1992;38:667–78.

    CAS  PubMed  Google Scholar 

  39. Armstrong DT, Kotaras PJ, Earl CR. Advances in production of embryos in vitro from juvenile and prepubertal oocytes from the calf and lamb. Reprod Fertil Dev. 1997;9:333–9.

    CAS  PubMed  Google Scholar 

  40. Ledda S, Bogliolo L, Leoni G, Naitana S. Production and lambing rate of blastocysts derived from in vitro matured oocytes after gonadotropin treatment of prepubertal ewes. J Anim Sci. 1999;77:2234–9.

    CAS  PubMed  Google Scholar 

  41. Revel F, Mermillod P, Peynot N, Renard JP, Heyman Y. Low developmental capacity of in vitro matured and fertilized oocytes from calves compared with that of cows. J Reprod Fertil. 1995;103:115–20.

    CAS  PubMed  Google Scholar 

  42. Leoni GG, Succu S, Berlinguer F, Rosati I, Bebbere D, Bogliolo L, et al. Delay on the in vitro kinetic development of prepubertal ovine embryos. Anim Reprod Sci. 2006;92:373–83.

    CAS  PubMed  Google Scholar 

  43. Leoni GG, Bebbere D, Succu S, Berlinguer F, Mossa F, Galioto M, et al. Relations between relative mRNA abundance and developmental competence of ovine oocytes. Mol Reprod Dev. 2007;74:249–57.

    CAS  PubMed  Google Scholar 

  44. Masala L, Burrai GP, Bellu E, Ariu F, Bogliolo L, Ledda S, et al. Methylation dynamics during folliculogenesis and early embryo development in sheep. Reproduction. 2017;153:605–19.

    CAS  PubMed  Google Scholar 

  45. Masala L, Ariu F, Bogliolo L, Bellu E, Ledda S, Bebbere D. Delay in maternal transcript degradation in ovine embryos derived from low competence oocytes. Mol Reprod Dev. 2018;85:427–39.

    CAS  PubMed  Google Scholar 

  46. Leoni GG, Palmerini MG, Satta V, Succu S, Pasciu V, Zinellu A, et al. Differences in the kinetic of the first meiotic division and in active mitochondrial distribution between prepubertal and adult oocytes mirror differences in their developmental competence in a sheep model. PLoS One. 2015;10:e0124911.

    PubMed  PubMed Central  Google Scholar 

  47. Svoboda P, Franke V, Schultz RM. Sculpting the transcriptome during the oocyte-to-embryo transition in mouse. Curr Top Dev Biol. 2015;113:305–49.

    CAS  PubMed  Google Scholar 

  48. Jiao ZX, Woodruff TK. Follicle microenvironment-associated alterations in gene expression in the mouse oocyte and its polar body. Fertil Steril. 2013;99:1453–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  49. Esposito G, Vitale AM, Leijten FP, Strik AM, Koonen-Reemst AM, Yurttas P, et al. Peptidylarginine deiminase (PAD) 6 is essential for oocyte cytoskeletal sheet formation and female fertility. Mol Cell Endocrinol. 2007;273:25–31.

    CAS  PubMed  Google Scholar 

  50. Chiang T, Duncan FE, Schindler K, Schultz RM, Lampson MA. Evidence that weakened centromere cohesion is a leading cause of age-related aneuploidy in oocytes. Curr Biol. 2010;20(17):1522–8.

    CAS  PubMed  PubMed Central  Google Scholar 

  51. Lister LM, Kouznetsova A, Hyslop LA, Kalleas D, Pace SL, Barel JC, et al. Age-related meiotic segregation errors in mammalian oocytes are preceded by depletion of cohesin and Sgo2. Curr Biol. 2010;20:1511–21.

    CAS  PubMed  Google Scholar 

  52. Gruhn JR, Zielinska AP, Shukla V, Blanshard R, Capalbo A, Cimadomo D, et al. Chromosome errors in human eggs shape natural fertility over reproductive life span. Science. 2019;365:1466–9.

    CAS  PubMed  PubMed Central  Google Scholar 

  53. Seidler EA, Moley KH. Metabolic determinants of mitochondrial function in oocytes. Semin Reprod Med. 2015;33:396–400.

    CAS  PubMed  Google Scholar 

  54. Bogliolo L, Ariu F, Leoni G, Uccheddu S, Bebbere D. High hydrostatic pressure treatment improves the quality of in vitro-produced ovine blastocysts. Reprod Fertil Dev. 2011;23:809–17.

    PubMed  Google Scholar 

  55. Docherty LE, Rezwan FI, Poole RL, Turner CL, Kivuva E, Maher ER, et al. Mutations in NLRP5 are associated with reproductive wastage and multilocus imprinting disorders in humans. Nat Commun. 2015;6:8086.

    PubMed  Google Scholar 

  56. Akoury E, Zhang L, Ao A, Slim R. NLRP7andKHDC3L, The two maternal effect proteins responsible for recurrent hydatidiform moles, co-localize to the oocyte cytoskeleton. Hum Reprod. 2015;30:159–69.

    CAS  PubMed  Google Scholar 

  57. Demond H, Anvar Z, Jahromi BN, Sparago A, Verma A, Davari M, et al. A KHDC3L mutation resulting in recurrent hydatidiform mole causes genome-wide DNA methylation loss in oocytes and persistent imprinting defects post-fertilisation. Genome Med. 2019;11:84.

    CAS  PubMed  PubMed Central  Google Scholar 

  58. Ivanova E, Canovas S, Garcia-Martínez S, Romar R, Lopes JS, Rizos D, et al. DNA methylation changes during preimplantation development reveal inter-species differences and reprogramming events at imprinted genes. Clin Epigenetics. 2020;12:64.

    CAS  PubMed  PubMed Central  Google Scholar 

  59. Zhu P, Guo H, Ren Y, Hou Y, Dong J, Li R, et al. Single-cell DNA methylome sequencing of human preimplantation embryos. Nat Genet. 2018;50:12–9.

    CAS  PubMed  Google Scholar 

  60. Kobayashi H, Sakurai T, Imai M, Takahashi N, Fukuda A, Yayoi O, et al. Contribution of intragenic DNA methylation in mouse gametic DNA methylomes to establish oocyte-specific heritable marks. PLoS Genet. 2012;8(1):e1002440.

    CAS  PubMed  PubMed Central  Google Scholar 

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Bebbere, D., Abazari-Kia, A., Nieddu, S. et al. Subcortical maternal complex (SCMC) expression during folliculogenesis is affected by oocyte donor age in sheep. J Assist Reprod Genet 37, 2259–2271 (2020). https://doi.org/10.1007/s10815-020-01871-x

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