{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T07:45:20Z","timestamp":1758613520174,"version":"3.44.0"},"reference-count":54,"publisher":"Oxford University Press (OUP)","issue":"3","license":[{"start":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T00:00:00Z","timestamp":1740355200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,5,14]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Adult ovarian tissues or biopsies isolated from patients prior to chemotherapy or irradiation can reconstitute ovarian functions when transplanted either in the abdomen or subcutaneously. Subcutaneously transplantation\u00a0avoids invasive surgery and potential risks associated with internal procedures. We investigated whether functional ovaries could develop subcutaneously from early E12.5 fetal gonads without entering meiosis in mouse model. Unexpectedly, the subcutaneously transplanted fetal gonads failed to undergo folliculogenesis in the recipient mice. The transplanted gonads experienced meiotic deficiency and exhibited significant defects in DNA repair and recombination, increased apoptosis levels. Meiotic defects in the subcutaneous grafts were partly attributable to variations in temperature and oxygen concentration. However, completion of meiotic prophase I was effectively achieved through in vitro culture of the gonads at 37\u00b0C. Subsequently, the in vitro cultured E12.5 gonads, following subcutaneous transplantation, became competent in folliculogenesis, restoring endocrine functions. This finding may have implications for rejuvenating ovarioids from fetal gonad-like cells using pluripotent stem cell technologies, as well as for enhancing endocrine recovery and health span.<\/jats:p>","DOI":"10.1093\/lifemedi\/lnaf007","type":"journal-article","created":{"date-parts":[[2025,2,24]],"date-time":"2025-02-24T09:11:22Z","timestamp":1740388282000},"source":"Crossref","is-referenced-by-count":0,"title":["Follicular development of fetal gonads under the skin of adult mice"],"prefix":"10.1093","volume":"4","author":[{"given":"Jiyu","family":"Chen","sequence":"first","affiliation":[{"name":"Department of Genetics and Cell Biology, College of Life Science, Nankai University , Tianjin 300071 ,","place":["China"]},{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300350 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chang","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Cell Biology, College of Life Science, Nankai University , Tianjin 300071 ,","place":["China"]},{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300350 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yongqin","family":"Yu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Cell Biology, College of Life Science, Nankai University , Tianjin 300071 ,","place":["China"]},{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300350 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoying","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Genetics and Cell Biology, College of Life Science, Nankai University , Tianjin 300071 ,","place":["China"]},{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300350 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9881-6830","authenticated-orcid":false,"given":"Lin","family":"Liu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Cell Biology, College of Life Science, Nankai University , Tianjin 300071 ,","place":["China"]},{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300350 ,","place":["China"]},{"name":"Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8734-8020","authenticated-orcid":false,"given":"Zhengmao","family":"Zhu","sequence":"additional","affiliation":[{"name":"Department of Genetics and Cell Biology, College of Life Science, Nankai University , Tianjin 300071 ,","place":["China"]},{"name":"State Key Laboratory of Medicinal Chemical Biology, Nankai University , Tianjin 300350 ,","place":["China"]},{"name":"Haihe Laboratory of Cell Ecosystem, Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300020 ,","place":["China"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2025,2,24]]},"reference":[{"key":"2025092302362619300_CIT0001","doi-asserted-by":"crossref","first-page":"1196","DOI":"10.1016\/S0140-6736(09)61460-4","article-title":"Ageing populations: the challenges ahead","volume":"374","author":"Christensen","year":"2009","journal-title":"Lancet"},{"key":"2025092302362619300_CIT0002","doi-asserted-by":"crossref","first-page":"881","DOI":"10.1093\/humrep\/dez015","article-title":"Variations in reproductive events across life: a pooled analysis of data from 505 147 women across 10 countries","volume":"34","author":"Inter","year":"2019","journal-title":"Hum Reprod"},{"key":"2025092302362619300_CIT0003","doi-asserted-by":"crossref","first-page":"470","DOI":"10.1038\/s41586-022-04463-0","article-title":"FSH blockade improves cognition in mice with Alzheimer\u2019s disease","volume":"603","author":"Xiong","year":"2022","journal-title":"Nature"},{"key":"2025092302362619300_CIT0004","doi-asserted-by":"crossref","first-page":"590","DOI":"10.1515\/mr-2022-0031","article-title":"Ovarian aging: mechanisms and intervention strategies","volume":"2","author":"Zhu","year":"2022","journal-title":"Medical review (2021)"},{"key":"2025092302362619300_CIT0005","doi-asserted-by":"crossref","first-page":"220","DOI":"10.1038\/nrendo.2016.164","article-title":"Hormone-replacement therapy: current thinking","volume":"13","author":"Lobo","year":"2017","journal-title":"Nat Rev Endocrinol"},{"key":"2025092302362619300_CIT0006","doi-asserted-by":"crossref","first-page":"1095627","DOI":"10.3389\/fendo.2022.1095627","article-title":"Ovarian tissue cryopreservation and transplantation: 20 years experience in Bologna University","volume":"13","author":"Fabbri","year":"2022","journal-title":"Front Endocrinol (Lausanne)"},{"key":"2025092302362619300_CIT0007","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1093\/humupd\/dmac003","article-title":"Fresh and cryopreserved ovarian tissue transplantation for preserving reproductive and endocrine function: a systematic review and individual patient data meta-analysis","volume":"28","author":"Khattak","year":"2022","journal-title":"Hum Reprod Update"},{"key":"2025092302362619300_CIT0008","doi-asserted-by":"crossref","first-page":"1102","DOI":"10.1016\/j.fertnstert.2021.03.008","article-title":"Transplantation of cryopreserved ovarian tissue in a series of 285 women: a review of five leading European centers","volume":"115","author":"Dolmans","year":"2021","journal-title":"Fertil Steril"},{"key":"2025092302362619300_CIT0009","doi-asserted-by":"crossref","first-page":"139","DOI":"10.1186\/s13048-022-01083-0","article-title":"Ovarian tissue transplantation ameliorates osteoporosis and dyslipidaemia in ovariectomised mice","volume":"15","author":"Zhou","year":"2022","journal-title":"J Ovarian Res"},{"key":"2025092302362619300_CIT0010","doi-asserted-by":"crossref","first-page":"113","DOI":"10.1016\/j.bpobgyn.2009.09.002","article-title":"Orthotopic and heterotopic ovarian tissue transplantation","volume":"24","author":"Sonmezer","year":"2010","journal-title":"Best Pract Res Clin Obstet Gynaecol"},{"key":"2025092302362619300_CIT0011","doi-asserted-by":"crossref","first-page":"31","DOI":"10.1530\/REP-22-0114","article-title":"Xenograft model of heterotopic transplantation of human ovarian cortical tissue and its clinical relevance","volume":"165","author":"Man","year":"2023","journal-title":"Reproduction"},{"key":"2025092302362619300_CIT0012","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1007\/s10815-017-1019-y","article-title":"Subcutaneous ovarian tissue transplantation in nonhuman primates: duration of endocrine function and normalcy of subsequent offspring as demonstrated by reproductive competence, oocyte production, and telomere length","volume":"34","author":"Lee","year":"2017","journal-title":"J Assist Reprod Genet"},{"key":"2025092302362619300_CIT0013","doi-asserted-by":"crossref","first-page":"315","DOI":"10.1530\/jrf.0.1070315","article-title":"Transplantation of cryopreserved fetal ovarian tissue to adult recipients in mice","volume":"107","author":"Cox","year":"1996","journal-title":"J Reprod Fertil"},{"key":"2025092302362619300_CIT0014","doi-asserted-by":"crossref","first-page":"1427","DOI":"10.1038\/s41598-017-01648-w","article-title":"Reconstitution of ovarian function following transplantation of primordial germ cells","volume":"7","author":"Zeng","year":"2017","journal-title":"Sci Rep"},{"key":"2025092302362619300_CIT0015","doi-asserted-by":"crossref","first-page":"567","DOI":"10.1089\/scd.2012.0436","article-title":"Recovery of functional oocytes from cultured premeiotic germ cells after kidney capsule transplantation","volume":"22","author":"Chen","year":"2013","journal-title":"Stem Cells Dev"},{"key":"2025092302362619300_CIT0016","doi-asserted-by":"crossref","first-page":"631","DOI":"10.1095\/biolreprod.110.087122","article-title":"Generation of functional oocytes and spermatids from fetal primordial germ cells after ectopic transplantation in adult mice","volume":"84","author":"Matoba","year":"2011","journal-title":"Biol Reprod"},{"key":"2025092302362619300_CIT0017","doi-asserted-by":"crossref","first-page":"54","DOI":"10.1093\/humrep\/dem334","article-title":"Mature oocytes derived from purified mouse fetal germ cells","volume":"23","author":"Qing","year":"2008","journal-title":"Hum Reprod"},{"key":"2025092302362619300_CIT0018","doi-asserted-by":"crossref","first-page":"233","DOI":"10.1111\/j.1440-169X.1992.tb00012.x","article-title":"Mouse offspring derived from fetal ovaries or reaggregates which were cultured and transplanted into adult females","volume":"34","author":"Hashimoto","year":"1992","journal-title":"Dev Growth Differentiation"},{"key":"2025092302362619300_CIT0019","doi-asserted-by":"crossref","first-page":"615","DOI":"10.1095\/biolreprod.106.051482","article-title":"Live offspring produced by mouse oocytes derived from premeiotic fetal germ cells","volume":"75","author":"Shen","year":"2006","journal-title":"Biol Reprod"},{"key":"2025092302362619300_CIT0020","doi-asserted-by":"crossref","first-page":"e13304","DOI":"10.1111\/acel.13304","article-title":"Mtor inhibition by INK128 extends functions of the ovary reconstituted from germline stem cells in aging and premature aging mice","volume":"20","author":"Heng","year":"2021","journal-title":"Aging Cell"},{"key":"2025092302362619300_CIT0021","doi-asserted-by":"crossref","first-page":"eabe0237","DOI":"10.1126\/science.abe0237","article-title":"Generation of ovarian follicles from mouse pluripotent stem cells","volume":"373","author":"Yoshino","year":"2021","journal-title":"Science"},{"key":"2025092302362619300_CIT0022","doi-asserted-by":"crossref","first-page":"356","DOI":"10.1126\/science.aat1674","article-title":"Generation of human oogonia from induced pluripotent stem cells in vitro","volume":"362","author":"Yamashiro","year":"2018","journal-title":"Science"},{"key":"2025092302362619300_CIT0023","doi-asserted-by":"crossref","first-page":"e87987","DOI":"10.7554\/eLife.87987","article-title":"Directed differentiation of human iPSCs to functional ovarian granulosa-like cells via transcription factor overexpression","volume":"12","author":"Pierson Smela","year":"2023","journal-title":"Elife"},{"key":"2025092302362619300_CIT0024","doi-asserted-by":"crossref","first-page":"e110815","DOI":"10.15252\/embj.2022110815","article-title":"Ex vivo reconstitution of fetal oocyte development in humans and cynomolgus monkeys","volume":"41","author":"Mizuta","year":"2022","journal-title":"EMBO J"},{"key":"2025092302362619300_CIT0025","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1038\/nature20104","article-title":"Reconstitution in vitro of the entire cycle of the mouse female germ line","volume":"539","author":"Hikabe","year":"2016","journal-title":"Nature"},{"key":"2025092302362619300_CIT0026","doi-asserted-by":"crossref","first-page":"4256","DOI":"10.1016\/j.celrep.2019.11.080","article-title":"Functional oocytes derived from granulosa cells","volume":"29","author":"Tian","year":"2019","journal-title":"Cell Rep"},{"key":"2025092302362619300_CIT0027","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1007\/s13238-021-00865-4","article-title":"Generation of developmentally competent oocytes and fertile mice from parthenogenetic embryonic stem cells","volume":"12","author":"Tian","year":"2021","journal-title":"Protein Cell"},{"key":"2025092302362619300_CIT0028","doi-asserted-by":"crossref","first-page":"5869","DOI":"10.1242\/dev.00804","article-title":"Mechanisms of germ cell specification across the metazoans: epigenesis and preformation","volume":"130","author":"Extavour","year":"2003","journal-title":"Development"},{"key":"2025092302362619300_CIT0029","doi-asserted-by":"crossref","first-page":"REVIEWS1017","DOI":"10.1186\/gb-2000-1-3-reviews1017","article-title":"The function and regulation of vasa-like genes in germ-cell development","volume":"1","author":"Raz","year":"2000","journal-title":"Genome Biol"},{"key":"2025092302362619300_CIT0030","doi-asserted-by":"crossref","first-page":"2053","DOI":"10.1093\/hmg\/ddi210","article-title":"Foxl2 is required for commitment to ovary differentiation","volume":"14","author":"Ottolenghi","year":"2005","journal-title":"Hum Mol Genet"},{"key":"2025092302362619300_CIT0031","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1083\/jcb.135.2.469","article-title":"Characterization of a premeiotic germ cell-specific cytoplasmic protein encoded by Stra8, a novel retinoic acid-responsive gene","volume":"135","author":"Oulad-Abdelghani","year":"1996","journal-title":"J Cell Biol"},{"key":"2025092302362619300_CIT0032","doi-asserted-by":"crossref","first-page":"14976","DOI":"10.1073\/pnas.0807297105","article-title":"Stra8 and its inducer, retinoic acid, regulate meiotic initiation in both spermatogenesis and oogenesis in mice","volume":"105","author":"Anderson","year":"2008","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025092302362619300_CIT0033","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1038\/85830","article-title":"Recombinational DNA double-strand breaks in mice precede synapsis","volume":"27","author":"Mahadevaiah","year":"2001","journal-title":"Nat Genet"},{"key":"2025092302362619300_CIT0034","doi-asserted-by":"crossref","first-page":"457","DOI":"10.1016\/0092-8674(92)90447-K","article-title":"Rad51 protein involved in repair and recombination in S. cerevisiae is a RecA-like protein","volume":"69","author":"Shinohara","year":"1992","journal-title":"Cell"},{"key":"2025092302362619300_CIT0035","doi-asserted-by":"crossref","first-page":"29","DOI":"10.1093\/humupd\/dmt049","article-title":"Blood and lymphatic vasculature in the ovary: development, function and disease","volume":"20","author":"Brown","year":"2014","journal-title":"Hum Reprod Update"},{"key":"2025092302362619300_CIT0036","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1007\/s10456-005-9004-y","article-title":"Vascular morphogenesis in the primate ovary","volume":"8","author":"Fraser","year":"2005","journal-title":"Angiogenesis"},{"key":"2025092302362619300_CIT0037","doi-asserted-by":"crossref","first-page":"18","DOI":"10.1186\/1477-7827-4-18","article-title":"Regulation of the ovarian follicular vasculature","volume":"4","author":"Fraser","year":"2006","journal-title":"Reprod Biol Endocrinol"},{"key":"2025092302362619300_CIT0038","first-page":"322","article-title":"Blood flow rate, temperature, oxygen tension and consumption in the skin of adults measured by a heated microcathode oxygen electrode","volume":"35","author":"Jaszczak","year":"1988","journal-title":"Dan Med Bull"},{"key":"2025092302362619300_CIT0039","doi-asserted-by":"crossref","first-page":"3479","DOI":"10.1016\/j.transproceed.2005.09.023","article-title":"Islet transplantation at subcutaneous and intramuscular sites","volume":"37","author":"Juang","year":"2005","journal-title":"Transplant Proc"},{"key":"2025092302362619300_CIT0040","doi-asserted-by":"crossref","first-page":"9337","DOI":"10.1073\/pnas.1619216114","article-title":"Modular tissue engineering for the vascularization of subcutaneously transplanted pancreatic islets","volume":"114","author":"Vlahos","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025092302362619300_CIT0041","doi-asserted-by":"crossref","first-page":"423","DOI":"10.1007\/s00266-022-03096-y","article-title":"Effect of hyperbaric oxygen therapy on the survival rate of autologous fat transplantation","volume":"47","author":"Liang","year":"2023","journal-title":"Aesthetic Plast Surg"},{"key":"2025092302362619300_CIT0042","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1111\/j.1467-789X.2009.00623.x","article-title":"Subcutaneous and visceral adipose tissue: structural and functional differences","volume":"11","author":"Ibrahim","year":"2010","journal-title":"Obes Rev"},{"key":"2025092302362619300_CIT0043","doi-asserted-by":"crossref","first-page":"1734","DOI":"10.1093\/humrep\/deq131","article-title":"Xenotransplantation of human ovarian tissue to nude mice: comparison between four grafting sites","volume":"25","author":"Dath","year":"2010","journal-title":"Hum Reprod"},{"key":"2025092302362619300_CIT0044","doi-asserted-by":"crossref","first-page":"4489","DOI":"10.1210\/jcem.86.9.7871","article-title":"Long-term ovarian function evaluation after autografting by implantation with fresh and frozen-thawed human ovarian tissue","volume":"86","author":"Callejo","year":"2001","journal-title":"J Clin Endocrinol Metab"},{"key":"2025092302362619300_CIT0045","doi-asserted-by":"crossref","first-page":"1167","DOI":"10.1007\/s10815-015-0544-9","article-title":"Ovarian cortex transplantation: 60 reported live births brings the success and worldwide expansion of the technique towards routine clinical practice","volume":"32","author":"Donnez","year":"2015","journal-title":"J Assist Reprod Genet"},{"key":"2025092302362619300_CIT0046","doi-asserted-by":"crossref","first-page":"276","DOI":"10.1038\/s41420-023-01577-w","article-title":"In vitro oogenesis from murine premeiotic germ cells using a new three-dimensional culture system","volume":"9","author":"Wang","year":"2023","journal-title":"Cell Death Discov"},{"key":"2025092302362619300_CIT0047","doi-asserted-by":"crossref","first-page":"12735","DOI":"10.3390\/ijms222312735","article-title":"The Roles of Luteinizing Hormone, Follicle-Stimulating Hormone and Testosterone in Spermatogenesis and Folliculogenesis Revisited","volume":"22","author":"Oduwole","year":"2021","journal-title":"Int J Mol Sci"},{"key":"2025092302362619300_CIT0048","doi-asserted-by":"crossref","first-page":"3775","DOI":"10.3390\/jcm13133775","article-title":"The roles of GDF-9, BMP-15, BMP-4 and EMMPRIN in Folliculogenesis and in vitro fertilization","volume":"13","author":"Fountas","year":"2024","journal-title":"J Clin Med"},{"key":"2025092302362619300_CIT0049","doi-asserted-by":"crossref","first-page":"854","DOI":"10.1016\/j.theriogenology.2014.11.026","article-title":"Transplantation of mouse ovarian tissue: comparison of the transplantation sites","volume":"83","author":"Youm","year":"2015","journal-title":"Theriogenology"},{"key":"2025092302362619300_CIT0050","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.cell.2014.12.013","article-title":"SOX17 is a critical specifier of human primordial germ cell fate","volume":"160","author":"Irie","year":"2015","journal-title":"Cell"},{"key":"2025092302362619300_CIT0051","doi-asserted-by":"crossref","first-page":"178","DOI":"10.1016\/j.stem.2015.06.014","article-title":"Robust in vitro induction of human germ cell fate from pluripotent stem cells","volume":"17","author":"Sasaki","year":"2015","journal-title":"Cell Stem Cell"},{"key":"2025092302362619300_CIT0052","doi-asserted-by":"crossref","first-page":"E9913","DOI":"10.1073\/pnas.1707779114","article-title":"Relevance of iPSC-derived human PGC-like cells at the surface of embryoid bodies to prechemotaxis migrating PGCs","volume":"114","author":"Mitsunaga","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2025092302362619300_CIT0053","doi-asserted-by":"crossref","first-page":"1733","DOI":"10.1038\/nprot.2017.070","article-title":"Reconstitution of mouse oogenesis in a dish from pluripotent stem cells","volume":"12","author":"Hayashi","year":"2017","journal-title":"Nat Protoc"},{"key":"2025092302362619300_CIT0054","doi-asserted-by":"crossref","first-page":"922","DOI":"10.1093\/humrep\/den466","article-title":"Effect of in vitro maturation of mouse oocytes on the health and lifespan of adult offspring","volume":"24","author":"Eppig","year":"2009","journal-title":"Hum Reprod"}],"container-title":["Life Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/lifemedi\/advance-article-pdf\/doi\/10.1093\/lifemedi\/lnaf007\/62111279\/lnaf007.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/lifemedi\/article-pdf\/4\/3\/lnaf007\/62111279\/lnaf007.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/lifemedi\/article-pdf\/4\/3\/lnaf007\/62111279\/lnaf007.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,9,23]],"date-time":"2025-09-23T06:36:40Z","timestamp":1758609400000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/lifemedi\/article\/doi\/10.1093\/lifemedi\/lnaf007\/8037801"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,2,24]]},"references-count":54,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2025,5,14]]}},"URL":"https:\/\/doi.org\/10.1093\/lifemedi\/lnaf007","relation":{},"ISSN":["2755-1733"],"issn-type":[{"type":"electronic","value":"2755-1733"}],"subject":[],"published-other":{"date-parts":[[2025,6]]},"published":{"date-parts":[[2025,2,24]]},"article-number":"lnaf007"}}