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In this study, we performed single-cell RNA sequencing analysis of control and RSA villous tissues and identified three subtypes of cytotrophoblasts (CTBs): CTB1, which is mainly involved in protein synthesis; CTB2, a highly proliferative progenitor population; and CTB3, an adhesive and invasive subtype that serves as the precursor of extravillous trophoblasts. We also characterized syncytiotrophoblasts, which are responsible for hormone production. In RSA villi, the functions of both CTBs and syncytiotrophoblasts were impaired. Notably, CTB2 and CTB3 exhibited pronounced features of cellular senescence, potentially contributing to reduced proliferative and differentiation capacity. These findings suggest that aberrant trophoblast senescence may underlie defective placentation in RSA and highlight potential therapeutic targets for restoring trophoblast function and improving pregnancy outcomes.<\/jats:p>","DOI":"10.1093\/reprod\/xaag030","type":"journal-article","created":{"date-parts":[[2026,3,18]],"date-time":"2026-03-18T17:39:16Z","timestamp":1773855556000},"source":"Crossref","is-referenced-by-count":1,"title":["Single-cell transcriptomics reveals cytotrophoblast subtypes and senescence in recurrent spontaneous abortion"],"prefix":"10.1093","volume":"171","author":[{"given":"Si-Man","family":"Chen","sequence":"first","affiliation":[{"name":"Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Obstetrics & Gynecology Hospital of Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Meng-Ying","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Obstetrics & Gynecology Hospital of Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yi-Xing","family":"Yang","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Obstetrics & Gynecology Hospital of Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nan","family":"Liu","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Obstetrics & Gynecology Hospital of Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Xiao","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Jinshan Hospital of Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiao-Yan","family":"Cao","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Obstetrics & Gynecology Hospital of Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2512-9703","authenticated-orcid":false,"given":"Xiao-Yong","family":"Zhu","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Obstetrics & Gynecology Hospital of Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9276-0722","authenticated-orcid":false,"given":"Ming-Qing","family":"Li","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Obstetrics & Gynecology Hospital of Fudan University , Shanghai,","place":["China"]},{"name":"Department of Reproductive Immunology, The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University , Shanghai,","place":["China"]},{"name":"Shanghai Key Laboratory of Embryo Original Diseases , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4867-6563","authenticated-orcid":false,"given":"Feng","family":"Xie","sequence":"additional","affiliation":[{"name":"Shanghai Key Lab of Reproduction and Development, Shanghai Key Lab of Female Reproductive Endocrine Related Diseases, Obstetrics & Gynecology Hospital of Fudan University , Shanghai,","place":["China"]},{"name":"Medical Center of Diagnosis and Treatment for Cervical Diseases, Obstetrics & Gynecology Hospital of Fudan University , Shanghai,","place":["China"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2026,3,18]]},"reference":[{"key":"2026040804085308900_xaag030-B1","doi-asserted-by":"publisher","first-page":"e1","DOI":"10.1111\/1471-0528.15968","article-title":"Reproductive implications and management of congenital uterine anomalies: scientific impact paper no. 62 November 2019","volume":"127","author":"Akhtar","year":"2020","journal-title":"BJOG: An International Journal of Obstetrics and Gynaecology"},{"key":"2026040804085308900_xaag030-B2","doi-asserted-by":"publisher","first-page":"479","DOI":"10.1038\/s41574-020-0372-6","article-title":"Tracking placental development in health and disease","volume":"16","author":"Aplin","year":"2020","journal-title":"Nature Reviews. 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