Abstract
Dynamic crosstalk between the embryo and mother is crucial during implantation. Here, we comprehensively profile the single-cell transcriptome of pig peri-implantation embryos and corresponding maternal endometrium, identifying 4 different lineages in embryos and 13 cell types in the endometrium. Cell-specific gene expression characterizes 4 distinct trophectoderm subpopulations, showing development from undifferentiated trophectoderm to polar and mural trophectoderm. Dynamic expression of genes in different types of endometrial cells illustrates their molecular response to embryos during implantation. Then, we developed a novel tool, ExtraCellTalk, generating an overall dynamic map of maternal-foetal crosstalk using uterine luminal proteins as bridges. Through cross-species comparisons, we identified a conserved RBP4/STRA6 pathway in which embryonic-derived RBP4 could target the STRA6 receptor on stromal cells to regulate the interaction with other endometrial cells. These results provide insight into the maternal-foetal crosstalk during embryo implantation and represent a valuable resource for further studies to improve embryo implantation.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
Data availability
The raw scRNA-seq data of pig embryo and endometrium samples generated in this study are available in the GEO database under accession number GSE222544. The mouse decidua bulk RNA sequencing data used in this study for comparison, are publicly available in the SRA database under accession number PRJNA921903. All other relevant data supporting the key findings of this study are available within the article and its Supplementary Information files. Source data are provided with this paper.
Code availability
ExtraCellTalk is publicly available as a Python program. Source code, as well as tutorials have been deposited in the GitHub repository (https://github.com/xupeng-zang/ExtraCellTalk). Custom scripts for processing and analysing data are available from the corresponding authors upon reasonable request.
References
Albini, A., and Noonan, D.M. (2021). Decidual-like NK cell polarization: from cancer killing to cancer nurturing. Cancer Discov 11, 28–33.
Arck, P.C., and Hecher, K. (2013). Fetomaternal immune cross-talk and its consequences for maternal and offspring’s health. Nat Med 19, 548–556.
Bazer, F.W., and Johnson, G.A. (2014). Pig blastocyst-uterine interactions. Differentiation 87, 52–65.
Bazer, F.W., Spencer, T.E., Johnson, G.A., Burghardt, R.C., and Wu, G. (2009a). Comparative aspects of implantation. Reproduction 138, 195–209.
Bazer, F.W., Wu, G., Spencer, T.E., Johnson, G.A., Burghardt, R.C., and Bayless, K. (2009b). Novel pathways for implantation and establishment and maintenance of pregnancy in mammals. Mol Hum Reprod 16, 135–152.
Benjamini, Y., and Hochberg, Y. (1995). Controlling the false discovery rate: a practical and powerful approach to multiple testing. J R Stat Soc 57, 289–300.
Bergen, V., Lange, M., Peidli, S., Wolf, F.A., and Theis, F.J. (2020). Generalizing RNA velocity to transient cell states through dynamical modeling. Nat Biotechnol 38, 1408–1414.
Bourdiec, A., Calvo, E., Rao, C., and Akoum, A. (2013). Transcriptome analysis reveals new insights into the modulation of endometrial stromal cell receptive phenotype by embryo-derived signals interleukin-1 and human chorionic gonadotropin: Possible involvement in early embryo implantation. PLoS ONE 8, e64829.
Brons, I.G.M., Smithers, L.E., Trotter, M.W.B., Rugg-Gunn, P., Sun, B., Chuva de Sousa Lopes, S.M., Howlett, S.K., Clarkson, A., Ahrlund-Richter, L., Pedersen, R.A., et al. (2007). Derivation of pluripotent epiblast stem cells from mammalian embryos. Nature 448, 191–195.
Browaeys, R., Saelens, W., and Saeys, Y. (2020). NicheNet: modeling intercellular communication by linking ligands to target genes. Nat Methods 17, 159–162.
Butler, A., Hoffman, P., Smibert, P., Papalexi, E., and Satija, R. (2018). Integrating single-cell transcriptomic data across different conditions, technologies, and species. Nat Biotechnol 36, 411–420.
Cabello-Aguilar, S., Alame, M., Kon-Sun-Tack, F., Fau, C., Lacroix, M., and Colinge, J. (2020). SingleCellSignalR: inference of intercellular networks from single-cell transcriptomics. Nucleic Acids Res 48, e55.
Carson, S.A., and Kallen, A.N. (2021). Diagnosis and management of infertility: a review. JAMA 326, 65–76.
Cencič, A., Guillomot, M., Koren, S., and La Bonnardière, C. (2003). Trophoblastic interferons: do they modulate uterine cellular markers at the time of conceptus attachment in the pig.? Placenta 24, 862–869.
Chen, Q., Zhang, Y., Peng, H., Lei, L., Kuang, H., Zhang, L., Ning, L., Cao, Y., and Duan, E. (2011). Transient β2-adrenoceptor activation confers pregnancy loss by disrupting embryo spacing at implantation. J Biol Chem 286, 4349–4356.
Chen, Y., Clarke, O.B., Kim, J., Stowe, S., Kim, Y.K., Assur, Z., Cavalier, M., Godoy-Ruiz, R., von Alpen, D.C., Manzini, C., et al. (2016). Structure of the STRA6 receptor for retinol uptake. Science 353, aad8266.
Choi, H., Sheng, J., Gao, D., Li, F., Durrans, A., Ryu, S., Lee, S.B., Narula, N., Rafii, S., Elemento, O., et al. (2015). Transcriptome analysis of individual stromal cell populations identifies stroma-tumor crosstalk in mouse lung cancer model. Cell Rep 10, 1187–1201.
Colombo, M., Raposo, G., and Théry, C. (2014). Biogenesis, secretion, and intercellular interactions of exosomes and other extracellular vesicles. Annu Rev Cell Dev Biol 30, 255–289.
Corachán, A., Pellicer, N., Pellicer, A., and Ferrero, H. (2021). Novel therapeutic targets to improve IVF outcomes in endometriosis patients: a review and future prospects. Hum Reprod Update 27, 923–972.
Dey, S.K., Lim, H., Das, S.K., Reese, J., Paria, B.C., Daikoku, T., and Wang, H. (2004). Molecular cues to implantation. Endocrine Rev 25, 341–373.
Du, M.R., Wang, S.C., and Li, D.J. (2014). The integrative roles of chemokines at the maternal-fetal interface in early pregnancy. Cell Mol Immunol 11, 438–448.
Efremova, M., Vento-Tormo, M., Teichmann, S.A., and Vento-Tormo, R. (2020). CellPhoneDB: inferring cell-cell communication from combined expression of multi-subunit ligand-receptor complexes. Nat Protoc 15, 1484–1506.
Geisert, R.D., Whyte, J.J., Meyer, A.E., Mathew, D.J., Juárez, M.R., Lucy, M.C., Prather, R.S., and Spencer, T.E. (2017). Rapid conceptus elongation in the pig: an interleukin 1 beta 2 and estrogen-regulated phenomenon. Mol Reprod Dev 84, 760–774.
Gliniak, C.M., Brown, J.M., and Noy, N. (2017). The retinol-binding protein receptor STRA6 regulates diurnal insulin responses. J Biol Chem 292, 15080–15093.
Gray, C.A., Bartol, F.F., Tarleton, B.J., Wiley, A.A., Johnson, G.A., Bazer, F.W., and Spencer, T.E. (2001). Developmental biology of uterine glands. Biol Reprod 65, 1311–1323.
Gulati, G.S., Sikandar, S.S., Wesche, D.J., Manjunath, A., Bharadwaj, A., Berger, M.J., Ilagan, F., Kuo, A.H., Hsieh, R.W., Cai, S., et al. (2020). Single-cell transcriptional diversity is a hallmark of developmental potential. Science 367, 405–411.
Hafemeister, C., and Satija, R. (2019). Normalization and variance stabilization of single-cell RNA-seq data using regularized negative binomial regression. Genome Biol 20, 1–5.
Hamatani, T., Daikoku, T., Wang, H., Matsumoto, H., Carter, M.G., Ko, M.S.H., and Dey, S.K. (2004). Global gene expression analysis identifies molecular pathways distinguishing blastocyst dormancy and activation. Proc Natl Acad Sci USA 101, 10326–10331.
He, Y.M., Li, X., Perego, M., Nefedova, Y., Kossenkov, A.V., Jensen, E.A., Kagan, V., Liu, Y.F., Fu, S.Y., Ye, Q.J., et al. (2018). Transitory presence of myeloid-derived suppressor cells in neonates is critical for control of inflammation. Nat Med 24, 224–231.
He, Y., Zang, X., Kuang, J., Yang, H., Gu, T., Yang, J., Li, Z., Zheng, E., Xu, Z., Cai, G., et al. (2022). iTRAQ-based quantitative proteomic analysis of porcine uterine fluid during pre-implantation period of pregnancy. J Proteomics 261, 104570.
Hong, L., Zang, X., Hu, Q., He, Y., Xu, Z., Xie, Y., Gu, T., Yang, H., Yang, J., Shi, J., et al. (2023). Uterine luminal-derived extracellular vesicles: potential nanomaterials to improve embryo implantation. J Nanobiotechnol 21, 79.
Hou, R., Denisenko, E., Ong, H.T., Ramilowski, J.A., and Forrest, A.R.R. (2020). Predicting cell-to-cell communication networks using NATMI. Nat Commun 11, 5011.
Huang, R., Bai, X., Li, X., Wang, X., and Zhao, L. (2021). Retinol-binding protein 4 activates STRA6, provoking pancreatic β-cell dysfunction in type 2 diabetes. Diabetes 70, 449–463.
Jin, Q., Yang, X., Gou, S., Liu, X., Zhuang, Z., Liang, Y., Shi, H., Huang, J., Wu, H., Zhao, Y., et al. (2022). Double knock-in pig models with elements of binary Tet-On and phiC31 integrase systems for controllable and switchable gene expression. Sci China Life Sci 65, 2269–2286.
Jin, S., Guerrero-Juarez, C.F., Zhang, L., Chang, I., Ramos, R., Kuan, C.H., Myung, P., Plikus, M.V., and Nie, Q. (2021). Inference and analysis of cell-cell communication using CellChat. Nat Commun 12, 1088.
Kaczmarek, M.M., Najmula, J., Guzewska, M.M., and Przygrodzka, E. (2020). MiRNAs in the peri-implantation period: contribution to embryo-maternal communication in pigs. IntJ Mol Sci 21, 2229.
La Manno, G., Soldatov, R., Zeisel, A., Braun, E., Hochgerner, H., Petukhov, V., Lidschreiber, K., Kastriti, M.E., Lönnerberg, P., Furlan, A., et al. (2018). RNA velocity of single cells. Nature 560, 494–498.
Lai, Z.Z., Wang, Y., Zhou, W.J., Liang, Z., Shi, J.W., Yang, H.L., Xie, F., Chen, W.D., Zhu, R., Zhang, C., et al. (2022). Single-cell transcriptome profiling of the human endometrium of patients with recurrent implantation failure. Theranostics 12, 6527–6547.
Li, R., Zhong, C., Yu, Y., Liu, H., Sakurai, M., Yu, L., Min, Z., Shi, L., Wei, Y., Takahashi, Y., et al. (2019). Generation of blastocyst-like structures from mouse embryonic and adult cell cultures. Cell 179, 687–702.e18.
Liao, Y., Smyth, G.K., and Shi, W. (2014). featureCounts: an efficient general purpose program for assigning sequence reads to genomic features. Bioinformatics 30, 923–930.
Liu, T., Li, J., Yu, L., Sun, H.X., Li, J., Dong, G., Hu, Y., Li, Y., Shen, Y., Wu, J., et al. (2021a). Cross-species single-cell transcriptomic analysis reveals pre-gastrulation developmental differences among pigs, monkeys, and humans. Cell Discov 7, 8.
Liu, X., Tan, J.P., Schröder, J., Aberkane, A., Ouyang, J.F., Mohenska, M., Lim, S.M., Sun, Y.B.Y., Chen, J., Sun, G., et al. (2021b). Modelling human blastocysts by reprogramming fibroblasts into iBlastoids. Nature 591, 627–632.
Love, M.I., Huber, W., and Anders, S. (2014). Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2. Genome Biol 15, 550.
Lunney, J.K., Van Goor, A., Walker, K.E., Hailstock, T., Franklin, J., and Dai, C. (2021). Importance of the pig as a human biomedical model. Sci Transl Med 13, eabd5758.
Lv, H., Zhao, G., Jiang, P., Wang, H., Wang, Z., Yao, S., Zhou, Z., Wang, L., Liu, D., Deng, W., et al. (2022). Deciphering the endometrial niche of human thin endometrium at single-cell resolution. Proc Natl Acad Sci USA 119, e2115912119.
Lyko, F. (2018). The DNA methyltransferase family: a versatile toolkit for epigenetic regulation. Nat Rev Genet 19, 81–92.
Machtinger, R., Laurent, L.C., and Baccarelli, A.A. (2016). Extracellular vesicles: roles in gamete maturation, fertilization and embryo implantation. Hum Reprod Update 22, 182–193.
Mattson, B.A., Overstrom, E.W., and Albertini, D.F. (1990). Transitions in trophectoderm cellular shape and cytoskeletal organization in the elongating pig blastocyst. Biol Reprod 42, 195–205.
McLendon, B.A., Seo, H., Kramer, A.C., Burghardt, R.C., Bazer, F.W., and Johnson, G. A. (2020). Pig conceptuses secrete interferon gamma to recruit T cells to the endometrium during the peri-implantation period. Biol Reprod 103, 1018–1029.
Mohammed, H., Hernando-Herraez, I., Savino, A., Scialdone, A., Macaulay, I., Mulas, C., Chandra, T., Voet, T., Dean, W., Nichols, J., et al. (2017). Single-cell landscape of transcriptional heterogeneity and cell fate decisions during mouse early gastrulation. Cell Rep 20, 1215–1228.
Mortazavi, A., Williams, B.A., McCue, K., Schaeffer, L., and Wold, B. (2008). Mapping and quantifying mammalian transcriptomes by RNA-Seq. Nat Methods 5, 621–628.
Nakajima, T., Iguchi, T., and Sato, T. (2016). Retinoic acid signaling determines the fate of uterine stroma in the mouse Müllerian duct. Proc Natl Acad Sci USA 113, 14354–14359.
Niakan, K.K., Han, J., Pedersen, R.A., Simon, C., and Pera, R.A.R. (2012). Human pre-implantation embryo development. Development 139, 829–841.
Noël, F., Massenet-Regad, L., Carmi-Levy, I., Cappuccio, A., Grandclaudon, M., Trichot, C., Kieffer, Y., Mechta-Grigoriou, F., and Soumelis, V. (2021). Dissection of intercellular communication using the transcriptome-based framework ICELLNET. Nat Commun 12, 1089.
Noy, N. (2016). Vitamin A in regulation of insulin responsiveness: mini review. Proc Nutr Soc 75, 212–215.
Ochiai, Y., Suzuki, C., Segawa, K., Uchiyama, Y., and Nagata, S. (2022). Inefficient development of syncytiotrophoblasts in the Atp11a-deficient mouse placenta. Proc Natl Acad Sci USA 119, e2200582119.
Pavlicev, M., Wagner, G.P., Chavan, A.R., Owens, K., Maziarz, J., Dunn-Fletcher, C., Kallapur, S.G., Muglia, L., and Jones, H. (2017). Single-cell transcriptomics of the human placenta: inferring the cell communication network of the maternal-fetal interface. Genome Res 27, 349–361.
Pawson, A.J., Sharman, J.L., Benson, H.E., Faccenda, E., Alexander, S.P.H., Buneman, O.P., Davenport, A.P., McGrath, J.C., Peters, J.A., Southan, C., et al. (2014). The IUPHAR/BPS Guide to PHARMACOLOGY: an expert-driven knowledgebase of drug targets and their ligands. Nucl Acids Res 42, D1098–D1106.
Pertea, M., Pertea, G.M., Antonescu, C.M., Chang, T.C., Mendell, J.T., and Salzberg, S. L. (2015). StringTie enables improved reconstruction of a transcriptome from RNA-seq reads. Nat Biotechnol 33, 290–295.
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.
Proctor, G.B. (2016). The physiology of salivary secretion. Periodontol 2000 70, 11–25.
Qiao, W., Wang, W., Laurenti, E., Turinsky, A.L., Wodak, S.J., Bader, G.D., Dick, J.E., and Zandstra, P.W. (2014). Intercellular network structure and regulatory motifs in the human hematopoietic system. Mol Syst Biol 10, 741.
Qiu, X., Hill, A., Packer, J., Lin, D., Ma, Y.A., and Trapnell, C. (2017). Single-cell mRNA quantification and differential analysis with Census. Nat Methods 14, 309–315.
Ramilowski, J.A., Goldberg, T., Harshbarger, J., Kloppmann, E., Lizio, M., Satagopam, V.P., Itoh, M., Kawaji, H., Carninci, P., Rost, B., et al. (2015). A draft network of ligand-receptor-mediated multicellular signalling in human. Nat Commun 6, 1–2.
Ramos-Ibeas, P., Sang, F., Zhu, Q., Tang, W.W.C., Withey, S., Klisch, D., Wood, L., Loose, M., Surani, M.A., and Alberio, R. (2019). Pluripotency and X chromosome dynamics revealed in pig pre-gastrulating embryos by single cell analysis. Nat Commun 10, 1–7.
Reardon, S.N., King, M.L., MacLean Ii, J.A., Mann, J.L., DeMayo, F.J., Lydon, J.P., and Hayashi, K. (2012). Cdh1 is essential for endometrial differentiation, gland development, and adult function in the mouse uterus. Biol Reprod 86.
Rickard, J.P., Ryan, G., Hall, E., de Graaf, S.P., and Hermes, R. (2017). Using transrectal ultrasound to examine the effect of exogenous progesterone on early embryonic loss in sheep. PLoS ONE 12, e0183659.
Robbins, P.D., and Morelli, A.E. (2014). Regulation of immune responses by extracellular vesicles. Nat Rev Immunol 14, 195–208.
Rohani, M.G., and Parks, W.C. (2015). Matrix remodeling by MMPs during wound repair. Matrix Biol 44–46, 113–121.
Rossant, J., and Tam, P.P.L. (2022). Early human embryonic development: Blastocyst formation to gastrulation. Dev Cell 57, 152–165.
Salamonsen, L.A., Evans, J., Nguyen, H.P.T., and Edgell, T.A. (2016). The microenvironment of human implantation: determinant of reproductive success. Am J Rep Immunol 75, 218–225.
Shao, X., Liao, J., Li, C., Lu, X., Cheng, J., and Fan, X. (2021). CellTalkDB: a manually curated database of ligand-receptor interactions in humans and mice. Brief Bioinf 22, bbaa269.
Shi, M., Chen, Z., Chen, M., Liu, J., Li, J., Xing, Z., Zhang, X., Lv, S., Li, X., Zuo, S., et al. (2021). Continuous activation of polymorphonuclear myeloid-derived suppressor cells during pregnancy is critical for fetal development. Cell Mol Immunol 18, 1692–1707.
Sidell, N., Feng, Y., Hao, L., Wu, J., Yu, J., Kane, M.A., Napoli, J.L., and Taylor, R.N. (2010). Retinoic acid is a cofactor for translational regulation of vascular endothelial growth factor in human endometrial stromal cells. Mol Endocrinol 24, 148–160.
Smith, K., Alnifaidy, R., Wei, Q., and Nieman, L.K. (2011). Endometrial Indian hedgehog expression is decreased in women with endometriosis. Fertility Sterility 95, 2738–2741.e3.
Smith, Z.D., and Meissner, A. (2013). DNA methylation: roles in mammalian development. Nat Rev Genet 14, 204–220.
Smyth, G.K. (2005). Limma: Linear models for microarray data. In: Gentleman, R., Carey, V.J., Huber, W., Irizarry, R.A., and Dudoit, S., eds. Bioinformatics and Computational Biology Solutions Using R and Bioconductor. Statistics for Biology and Health. New York: Springer. 397–420.
Suhorutshenko, M., Kukushkina, V., Velthut-Meikas, A., Altmäe, S., Peters, M., Mägi, R., Krjutškov, K., Koel, M., Codoner, F.M., Martinez-Blanch, J.F., et al. (2018). Endometrial receptivity revisited: endometrial transcriptome adjusted for tissue cellular heterogeneity. Hum Reprod 33, 2074–2086.
Sun, Y., Yang, Y., Jiang, Z., Wang, F., Han, K., Hong, L., Cao, J., and Yu, M. (2022). C/EBP-β contributes to pig endometrial LE receptivity by targeting cell remodeling genes during implantation. Reproduction 164, 269–281.
Suryawanshi, H., Morozov, P., Straus, A., Sahasrabudhe, N., Max, K.E.A., Garzia, A., Kustagi, M., Tuschl, T., and Williams, Z. (2018). A single-cell survey of the human first-trimester placenta and decidua. Sci Adv 4, eaau4788.
Thumuluri, V., Almagro Armenteros, J.J., Johansen, A.R., Nielsen, H., and Winther, O. (2022). DeepLoc 2.0: multi-label subcellular localization prediction using protein language models. Nucleic Acids Res 50, W228–W234.
Turco, M.Y., and Moffett, A. (2019). Development of the human placenta. Development 146, dev163428.
Türei, D., Valdeolivas, A., Gul, L., Palacio-Escat, N., Klein, M., Ivanova, O., Ölbei, M., Gábor, A., Theis, F., Módos, D., et al. (2021). Integrated intra- and intercellular signaling knowledge for multicellular omics analysis. Mol Syst Biol 17, e9923.
Van de Sande, B., Flerin, C., Davie, K., De Waegeneer, M., Hulselmans, G., Aibar, S., Seurinck, R., Saelens, W., Cannoodt, R., Rouchon, Q., et al. (2020). A scalable SCENIC workflow for single-cell gene regulatory network analysis. Nat Protoc 15, 2247–2276.
Veeck, J., Chorovicer, M., Naami, A., Breuer, E., Zafrakas, M., Bektas, N., Dürst, M., Kristiansen, G., Wild, P.J., Hartmann, A., et al. (2008). The extracellular matrix protein ITIH5 is a novel prognostic marker in invasive node-negative breast cancer and its aberrant expression is caused by promoter hypermethylation. Oncogene 27, 865–876.
Vento-Tormo, R., Efremova, M., Botting, R.A., Turco, M.Y., Vento-Tormo, M., Meyer, K.B., Park, J.E., Stephenson, E., Polanski, K., Goncalves, A., et al. (2018). Single-cell reconstruction of the early maternal-fetal interface in humans. Nature 563, 347–353.
Wang, W., Vilella, F., Alama, P., Moreno, I., Mignardi, M., Isakova, A., Pan, W., Simon, C., and Quake, S.R. (2020). Single-cell transcriptomic atlas of the human endometrium during the menstrual cycle. Nat Med 26, 1644–1653.
Wang, Y., Wang, R., Zhang, S., Song, S., Jiang, C., Han, G., Wang, M., Ajani, J., Futreal, A., and Wang, L. (2019). Italk: an R package to characterize and illustrate intercellular communication. bioRxiv 507871.
Wang, Y., Xue, S., Liu, X., Liu, H., Hu, T., Qiu, X., Zhang, J., and Lei, M. (2016). Analyses of Long Non-Coding RNA and mRNA profiling using RNA sequencing during the pre-implantation phases in pig endometrium. Sci Rep 6, 20238.
Weis, W.I., and Kobilka, B.K. (2018). The molecular basis of G protein-coupled receptor activation. Annu Rev Biochem 87, 897–919.
Whyte, J.J., Meyer, A.E., Spate, L.D., Benne, J.A., Cecil, R., Samuel, M.S., Murphy, C. N., Prather, R.S., and Geisert, R.D. (2018). Inactivation of porcine interleukin-1 β results in failure of rapid conceptus elongation. Proc Natl Acad Sci USA 115, 307–312.
Wilcox, A.J., Weinberg, C.R., O’Connor, J.F., Baird, D.D., Schlatterer, J.P., Canfield, R. E., Armstrong, E.G., and Nisula, B.C. (1988). Incidence of early loss of pregnancy. N Engl J Med 319, 189–194.
Wiltbank, M.C., Baez, G.M., Garcia-Guerra, A., Toledo, M.Z., Monteiro, P.L.J., Melo, L. F., Ochoa, J.C., Santos, J.E.P., and Sartori, R. (2016). Pivotal periods for pregnancy loss during the first trimester of gestation in lactating dairy cows. Theriogenology 86, 239–253.
Wu, B., Wang, Y., Yan, J., Liu, M., Li, X., Tang, F., and Bao, S. (2024). Blastoids generated purely from embryonic stem cells both in mice and humans. Sci China Life Sci 67, 418–420.
Wu, T., Hu, E., Xu, S., Chen, M., Guo, P., Dai, Z., Feng, T., Zhou, L., Tang, W., Zhan, L., et al. (2021). clusterProfiler 4.0: a universal enrichment tool for interpreting omics data. Innovation 2, 100141.
Ximerakis, M., Lipnick, S.L., Innes, B.T., Simmons, S.K., Adiconis, X., Dionne, D., Mayweather, B.A., Nguyen, L., Niziolek, Z., Ozek, C., et al. (2019). Single-cell transcriptomic profiling of the aging mouse brain. Nat Neurosci 22, 1696–1708.
Yang, Y., Zhu, Q., and Liu, J. (2021). Deciphering mouse uterine receptivity for embryo implantation at single-cell resolution. Cell Proliferation 54, e13128.
Ye, X., Hama, K., Contos, J.J.A., Anliker, B., Inoue, A., Skinner, M.K., Suzuki, H., Amano, T., Kennedy, G., Arai, H., et al. (2005). LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing. Nature 435, 104–108.
Yoshihara, K., Shahmoradgoli, M., Martinez, E., Vegesna, R., Kim, H., Torres-Garcia, W., Trevino, V., Shen, H., Laird, P.W., Levine, D.A., et al. (2013). Inferring tumour purity and stromal and immune cell admixture from expression data. Nat Commun 4, 1.
Yu, L., Wei, Y., Duan, J., Schmitz, D.A., Sakurai, M., Wang, L., Wang, K., Zhao, S., Hon, G.C., and Wu, J. (2021). Blastocyst-like structures generated from human pluripotent stem cells. Nature 591, 620–626.
Zang, X., Gu, T., Hu, Q., Xu, Z., Xie, Y., Zhou, C., Zheng, E., Huang, S., Xu, Z., Meng, F., et al. (2021). Global transcriptomic analyses reveal genes involved in conceptus development during the implantation stages in pigs. Front Genet 12, 584995.
Zhi, M., Zhang, J., Tang, Q., Yu, D., Gao, S., Gao, D., Liu, P., Guo, J., Hai, T., Gao, J., et al. (2022). Generation and characterization of stable pig pregastrulation epiblast stem cell lines. Cell Res 32, 383–400.
Zhou, F., Wang, R., Yuan, P., Ren, Y., Mao, Y., Li, R., Lian, Y., Li, J., Wen, L., Yan, L., et al. (2019). Reconstituting the transcriptome and DNA methylome landscapes of human implantation. Nature 572, 660–664.
Zhu, H., Li, T., Xu, P., Ding, L., Zhu, X., Wang, B., Tang, X., Li, J., Zhu, P., Wang, H., et al. (2024). Effect of autologous bone marrow stem cells-scaffold transplantation on the ongoing pregnancy rate in intrauterine adhesion women: a randomized, controlled trial. Sci China Life Sci 67, 113–121.
Zhu, Y., Zhou, Z., Huang, T., Zhang, Z., Li, W., Ling, Z., Jiang, T., Yang, J., Yang, S., Xiao, Y., et al. (2022). Mapping and analysis of a spatiotemporal H3K27ac and gene expression spectrum in pigs. Sci China Life Sci 65, 1517–1534.
Acknowledgement
This work was supported by the National Key Research and Development Program of China (2021YFD1301103), the National Natural Science Foundation of China (31802033), the Guangdong Provincial Key Area Research and Development Program (2022B0202090002), the Guangdong Basic and Applied Basic Research Foundation (2022A1515011131, 2023A1515030193) and the Guangdong Provincial Promotion Project on Preservation and Utilization of Local Breed of Livestock and Poultry (2018143).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
The author(s) declare that they have no conflict of interest.
Rights and permissions
About this article
Cite this article
Zang, X., Gu, S., Wang, W. et al. Dynamic intrauterine crosstalk promotes porcine embryo implantation during early pregnancy. Sci. China Life Sci. (2024). https://doi.org/10.1007/s11427-023-2557-x
Received:
Accepted:
Published:
DOI: https://doi.org/10.1007/s11427-023-2557-x