{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,1,30]],"date-time":"2026-01-30T04:34:21Z","timestamp":1769747661672,"version":"3.49.0"},"reference-count":59,"publisher":"Oxford University Press (OUP)","issue":"4","license":[{"start":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T00:00:00Z","timestamp":1653004800000},"content-version":"vor","delay-in-days":1,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["32171113"],"award-info":[{"award-number":["32171113"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["31972910"],"award-info":[{"award-number":["31972910"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["82071723"],"award-info":[{"award-number":["82071723"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001809","name":"National Natural Science Foundation of China","doi-asserted-by":"publisher","award":["81871162"],"award-info":[{"award-number":["81871162"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2021A1515010774"],"award-info":[{"award-number":["2021A1515010774"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2021B1515020069"],"award-info":[{"award-number":["2021B1515020069"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100021171","name":"Guangdong Basic and Applied Basic Research Foundation","doi-asserted-by":"publisher","award":["2019A1515010755"],"award-info":[{"award-number":["2019A1515010755"]}],"id":[{"id":"10.13039\/501100021171","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Guangdong Medical Science and Technology Research Foundation","award":["A2020080"],"award-info":[{"award-number":["A2020080"]}]},{"name":"Science and Technology Project of Guangzhou","award":["202002030063"],"award-info":[{"award-number":["202002030063"]}]},{"name":"Health Science and Technology Project of Guangzhou","award":["20201A011016"],"award-info":[{"award-number":["20201A011016"]}]},{"name":"Health Science and Technology Project of Guangzhou","award":["201904010024"],"award-info":[{"award-number":["201904010024"]}]},{"name":"Scientific Program of Dongguan People\u2019s Hospital","award":["K202022"],"award-info":[{"award-number":["K202022"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2022,10,11]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>In mammals, testis development is triggered by the expression of the sex-determining Y-chromosome gene SRY to commit the Sertoli cell (SC) fate at gonadal sex determination in the fetus. Several genes have been identified to be required to promote the testis pathway following SRY activation (i.e., SRY box 9 (SOX9)) in an embryo; however, it largely remains unknown about the genes and the mechanisms involved in stabilizing the testis pathway after birth and throughout adulthood. Herein, we report postnatal males with SC-specific deletion of Raptor demonstrated the absence of SC unique identity and adversely acquired granulosa cell-like characteristics, along with loss of tubular architecture and scattered distribution of SCs and germ cells. Subsequent genome-wide analysis by RNA sequencing revealed a profound decrease in the transcripts of testis genes (i.e., Sox9, Sox8, and anti-Mullerian hormone (Amh)) and, conversely, an increase in ovary genes (i.e., LIM\/Homeobox gene 9 (Lhx9), Forkhead box L2 (Foxl2) and Follistatin (Fst)); these changes were further confirmed by immunofluorescence and quantitative reverse-transcription polymerase chain reaction. Importantly, co-immunofluorescence demonstrated that Raptor deficiency induced SCs dedifferentiation into a progenitor state; the Raptor-mutant gonads showed some ovarian somatic cell features, accompanied by enhanced female steroidogenesis and elevated estrogen levels, yet the zona pellucida 3 (ZP3)-positive terminally feminized oocytes were not observed. In vitro experiments with primary SCs suggested that Raptor is likely involved in the fibroblast growth factor 9 (FGF9)-induced formation of cell junctions among SCs. Our results established that Raptor is required to maintain SC identity, stabilize the male pathway, and promote testis development.<\/jats:p>","DOI":"10.1093\/biolre\/ioac104","type":"journal-article","created":{"date-parts":[[2022,5,20]],"date-time":"2022-05-20T19:21:32Z","timestamp":1653074492000},"page":"1125-1138","source":"Crossref","is-referenced-by-count":5,"title":["Loss of <i>Raptor<\/i> induces Sertoli cells into an undifferentiated state in mice"],"prefix":"10.1093","volume":"107","author":[{"given":"Minyu","family":"Xie","sequence":"first","affiliation":[{"name":"Department of Obstetrics and Gynecology, Center for Reproductive Medicine; Department of Fetal Medicine and Prenatal Diagnosis, BioResource Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou Guangdong , China"},{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiao","family":"Hu","sequence":"additional","affiliation":[{"name":"Department of Plastic and Burn Surgery, Guangzhou Red Cross Hospital, Jinan University Faculty of Medical Science , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lei","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Center for Reproductive Medicine; Department of Fetal Medicine and Prenatal Diagnosis, BioResource Research Center, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhi","family":"Xiong","sequence":"additional","affiliation":[{"name":"Bioland Laboratory (Guangzhou Regenerative Medicine and Health Guangdong Laboratory) , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hanbin","family":"Zhang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuge","family":"Zhuang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zicong","family":"Huang","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jinsheng","family":"Liu","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jingyao","family":"Lian","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Chuyu","family":"Huang","sequence":"additional","affiliation":[{"name":"Center for Reproductive Medicine, Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Qiang","family":"Xie","sequence":"additional","affiliation":[{"name":"Center for Reproduction, Affiliated Dongguan Hospital, Southern Medical University (Dongguan People\u2019s Hospital) , Dongguan, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiangjin","family":"Kang","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yong","family":"Fan","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Guangdong Provincial Key Laboratory of Major Obstetric Diseases, Key Laboratory of Reproduction and Genetics of Guangdong Higher Education Institutes, The Third Affiliated Hospital of Guangzhou Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaochun","family":"Bai","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zhenguo","family":"Chen","sequence":"additional","affiliation":[{"name":"Guangdong Provincial Key Laboratory of Construction and Detection in Tissue Engineering, Department of Cell Biology, School of Basic Medical Sciences, Southern Medical University , Guangzhou, Guangdong , China"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2022,5,19]]},"reference":[{"key":"2022121212363933600_ref1","doi-asserted-by":"crossref","first-page":"245","DOI":"10.1038\/346245a0","article-title":"A gene mapping to the sex-determining region of the mouse Y chromosome is a member of a novel family of embryonically expressed genes","volume":"346","author":"Gubbay","year":"1990","journal-title":"Nature"},{"key":"2022121212363933600_ref2","doi-asserted-by":"crossref","first-page":"117","DOI":"10.1038\/351117a0","article-title":"Male development of chromosomally female mice transgenic for Sry","volume":"351","author":"Koopman","year":"1991","journal-title":"Nature"},{"key":"2022121212363933600_ref3","doi-asserted-by":"crossref","first-page":"201","DOI":"10.1002\/dvdy.1134","article-title":"Spatially dynamic expression of Sry in mouse genital ridges","volume":"221","author":"Bullejos","year":"2001","journal-title":"Dev Dyn"},{"key":"2022121212363933600_ref4","doi-asserted-by":"crossref","first-page":"1603","DOI":"10.1242\/dev.121.6.1603","article-title":"Expression of Sry, the mouse sex determining gene","volume":"121","author":"Hacker","year":"1995","journal-title":"Development"},{"key":"2022121212363933600_ref5","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1016\/j.ydbio.2004.07.011","article-title":"SOX9 is up-regulated by the transient expression of SRY specifically in Sertoli cell precursors","volume":"274","author":"Sekido","year":"2004","journal-title":"Dev Biol"},{"key":"2022121212363933600_ref6","doi-asserted-by":"crossref","first-page":"10553","DOI":"10.1074\/jbc.M609578200","article-title":"SOX9 regulates prostaglandin D synthase gene transcription in vivo to ensure testis development","volume":"282","author":"Wilhelm","year":"2007","journal-title":"J Biol Chem"},{"key":"2022121212363933600_ref7","doi-asserted-by":"crossref","first-page":"1798","DOI":"10.1038\/sj.emboj.7600660","article-title":"Prostaglandin D2 induces nuclear import of the sex-determining factor SOX9 via its cAMP-PKA phosphorylation","volume":"24","author":"Malki","year":"2005","journal-title":"EMBO J"},{"key":"2022121212363933600_ref8","doi-asserted-by":"crossref","first-page":"111","DOI":"10.1016\/j.ydbio.2005.08.039","article-title":"Sertoli cell differentiation is induced both cell-autonomously and through prostaglandin signaling during mammalian sex determination","volume":"287","author":"Wilhelm","year":"2005","journal-title":"Dev Biol"},{"key":"2022121212363933600_ref9","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pbio.0040187","article-title":"Fgf9 and Wnt4 act as antagonistic signals to regulate mammalian sex determination","volume":"4","author":"Kim","year":"2006","journal-title":"PLoS Biol"},{"key":"2022121212363933600_ref10","doi-asserted-by":"crossref","first-page":"195","DOI":"10.1016\/bs.ctdb.2019.01.008","article-title":"Role of epigenetic regulation in mammalian sex determination","volume":"134","author":"Miyawaki","year":"2019","journal-title":"Curr Top Dev Biol"},{"key":"2022121212363933600_ref11","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1159\/000520007","article-title":"The chromatin state during gonadal sex determination","volume":"15","author":"Dupont","year":"2021","journal-title":"Sex Dev"},{"key":"2022121212363933600_ref12","doi-asserted-by":"crossref","first-page":"1278","DOI":"10.1093\/hmg\/ddn036","article-title":"R-spondin1 plays an essential role in ovarian development through positively regulating Wnt-4 signaling","volume":"17","author":"Tomizuka","year":"2008","journal-title":"Hum Mol Genet"},{"key":"2022121212363933600_ref13","doi-asserted-by":"crossref","first-page":"1264","DOI":"10.1093\/hmg\/ddn016","article-title":"Activation of beta-catenin signaling by Rspo1 controls differentiation of the mammalian ovary","volume":"17","author":"Chassot","year":"2008","journal-title":"Hum Mol Genet"},{"key":"2022121212363933600_ref14","doi-asserted-by":"crossref","first-page":"R97","DOI":"10.1530\/REP-14-0177","article-title":"R-spondin1, WNT4, and the CTNNB1 signaling pathway: strict control over ovarian differentiation","volume":"148","author":"Chassot","year":"2014","journal-title":"Reproduction"},{"key":"2022121212363933600_ref15","doi-asserted-by":"crossref","first-page":"17577","DOI":"10.1074\/jbc.M117.811349","article-title":"Beta-catenin directs the transformation of testis Sertoli cells to ovarian granulosa-like cells by inducing Foxl2 expression","volume":"292","author":"Li","year":"2017","journal-title":"J Biol Chem"},{"key":"2022121212363933600_ref16","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":"2022121212363933600_ref17","doi-asserted-by":"crossref","first-page":"1130","DOI":"10.1016\/j.cell.2009.11.021","article-title":"Somatic sex reprogramming of adult ovaries to testes by FOXL2 ablation","volume":"139","author":"Uhlenhaut","year":"2009","journal-title":"Cell"},{"key":"2022121212363933600_ref18","doi-asserted-by":"crossref","first-page":"210","DOI":"10.1002\/dvdy.20042","article-title":"Follistatin operates downstream of Wnt4 in mammalian ovary organogenesis","volume":"230","author":"Yao","year":"2004","journal-title":"Dev Dyn"},{"key":"2022121212363933600_ref19","doi-asserted-by":"crossref","first-page":"1433","DOI":"10.1101\/gad.981202","article-title":"Desert hedgehog\/patched 1 signaling specifies fetal Leydig cell fate in testis organogenesis","volume":"16","author":"Yao","year":"2002","journal-title":"Genes Dev"},{"key":"2022121212363933600_ref20","doi-asserted-by":"crossref","first-page":"800","DOI":"10.1101\/gad.1052503","article-title":"Pdgfr-alpha mediates testis cord organization and fetal Leydig cell development in the XY gonad","volume":"17","author":"Brennan","year":"2003","journal-title":"Genes Dev"},{"key":"2022121212363933600_ref21","doi-asserted-by":"crossref","first-page":"11987","DOI":"10.1073\/pnas.0600994103","article-title":"The Wilms tumor gene, Wt1, is required for Sox9 expression and maintenance of tubular architecture in the developing testis","volume":"103","author":"Gao","year":"2006","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022121212363933600_ref22","doi-asserted-by":"crossref","DOI":"10.1371\/journal.pgen.1007895","article-title":"CBX2 is required to stabilize the testis pathway by repressing Wnt signaling","volume":"15","author":"Garcia-Moreno","year":"2019","journal-title":"PLoS Genet"},{"key":"2022121212363933600_ref23","doi-asserted-by":"crossref","first-page":"32","DOI":"10.1038\/ng1141","article-title":"Dax1 is required for testis determination","volume":"34","author":"Meeks","year":"2003","journal-title":"Nat Genet"},{"key":"2022121212363933600_ref24","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1038\/35799","article-title":"Dax1 antagonizes Sry action in mammalian sex determination","volume":"391","author":"Swain","year":"1998","journal-title":"Nature"},{"key":"2022121212363933600_ref25","doi-asserted-by":"crossref","first-page":"487","DOI":"10.1016\/j.ajhg.2018.01.021","article-title":"Loss of function of the nuclear receptor NR2F2, encoding COUP-TF2, causes testis development and cardiac defects in 46","volume":"102","author":"Bashamboo","year":"2018","journal-title":"XX Children Am J Hum Genet"},{"key":"2022121212363933600_ref26","doi-asserted-by":"crossref","first-page":"5116","DOI":"10.1038\/s41467-019-13060-1","article-title":"RUNX1 maintains the identity of the fetal ovary through an interplay with FOXL2","volume":"10","author":"Nicol","year":"2019","journal-title":"Nat Commun"},{"key":"2022121212363933600_ref27","doi-asserted-by":"crossref","first-page":"101","DOI":"10.1038\/nature10239","article-title":"DMRT1 prevents female reprogramming in the postnatal mammalian testis","volume":"476","author":"Matson","year":"2011","journal-title":"Nature"},{"key":"2022121212363933600_ref28","doi-asserted-by":"crossref","first-page":"239","DOI":"10.1007\/s00018-009-0163-7","article-title":"Key factors in mTOR regulation","volume":"67","author":"Bai","year":"2010","journal-title":"Cell Mol Life Sci"},{"key":"2022121212363933600_ref29","doi-asserted-by":"crossref","first-page":"183","DOI":"10.1038\/s41580-019-0199-y","article-title":"mTOR at the nexus of nutrition, growth, ageing and disease","volume":"21","author":"Liu","year":"2020","journal-title":"Nat Rev Mol Cell Biol"},{"key":"2022121212363933600_ref30","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1007\/978-981-15-0602-4_3","article-title":"Regulation of autophagy by mTOR signaling pathway","volume":"1206","author":"Wang","year":"2019","journal-title":"Adv Exp Med Biol"},{"key":"2022121212363933600_ref31","doi-asserted-by":"crossref","first-page":"72","DOI":"10.1016\/j.ceb.2017.02.012","article-title":"mTORC1 signaling and the metabolic control of cell growth","volume":"45","author":"Ben-Sahra","year":"2017","journal-title":"Curr Opin Cell Biol"},{"key":"2022121212363933600_ref32","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1095\/biolreprod.116.140947","article-title":"mTORC1 activation promotes spermatogonial differentiation and causes subfertility in mice","volume":"95","author":"Wang","year":"2016","journal-title":"Biol Reprod"},{"key":"2022121212363933600_ref33","doi-asserted-by":"crossref","first-page":"467","DOI":"10.15252\/embr.201439379","article-title":"Distinct germline progenitor subsets defined through Tsc2-mTORC1 signaling","volume":"16","author":"Hobbs","year":"2015","journal-title":"EMBO Rep"},{"key":"2022121212363933600_ref34","doi-asserted-by":"crossref","first-page":"4244","DOI":"10.1210\/en.2015-1217","article-title":"Rictor regulates spermatogenesis by controlling Sertoli cell cytoskeletal organization and cell polarity in the mouse testis","volume":"156","author":"Dong","year":"2015","journal-title":"Endocrinology"},{"key":"2022121212363933600_ref35","doi-asserted-by":"crossref","first-page":"1289","DOI":"10.1093\/biolre\/ioy144","article-title":"Raptor directs Sertoli cell cytoskeletal organization and polarity in the mouse testis","volume":"99","author":"Xiong","year":"2018","journal-title":"Biol Reprod"},{"key":"2022121212363933600_ref36","doi-asserted-by":"crossref","first-page":"291","DOI":"10.1016\/B978-0-12-407704-1.00006-3","article-title":"Regulation of blood-testis barrier (BTB) dynamics during spermatogenesis via the \"Yin\" and \"Yang\" effects of mammalian target of rapamycin complex 1 (mTORC1) and mTORC2","volume":"301","author":"Mok","year":"2013","journal-title":"Int Rev Cell Mol Biol"},{"key":"2022121212363933600_ref37","doi-asserted-by":"crossref","first-page":"13","DOI":"10.1095\/biolreprod.115.138016","article-title":"mTOR regulates gap junction alpha-1 protein trafficking in Sertoli cells and is required for the maintenance of spermatogenesis in mice","volume":"95","author":"Boyer","year":"2016","journal-title":"Biol Reprod"},{"key":"2022121212363933600_ref38","doi-asserted-by":"crossref","first-page":"E5326","DOI":"10.1073\/pnas.1800352115","article-title":"Oocyte stage-specific effects of MTOR determine granulosa cell fate and oocyte quality in mice","volume":"115","author":"Guo","year":"2018","journal-title":"Proc Natl Acad Sci U S A"},{"key":"2022121212363933600_ref39","doi-asserted-by":"crossref","first-page":"1060","DOI":"10.1095\/biolreprod.107.061242","article-title":"Peroxisomes in human and mouse testis: differential expression of peroxisomal proteins in germ cells and distinct somatic cell types of the testis","volume":"77","author":"Nenicu","year":"2007","journal-title":"Biol Reprod"},{"key":"2022121212363933600_ref40","doi-asserted-by":"crossref","first-page":"1891","DOI":"10.1242\/dev.01087","article-title":"Functional analysis of Sox8 and Sox9 during sex determination in the mouse","volume":"131","author":"Chaboissier","year":"2004","journal-title":"Development"},{"key":"2022121212363933600_ref41","doi-asserted-by":"crossref","first-page":"281","DOI":"10.1159\/000364935","article-title":"Molecular genetics of Mullerian duct formation, regression and differentiation","volume":"8","author":"Mullen","year":"2014","journal-title":"Sex Dev"},{"key":"2022121212363933600_ref42","doi-asserted-by":"crossref","first-page":"398","DOI":"10.1016\/S0006-291X(88)81099-4","article-title":"Rat clusterin isolated from primary Sertoli cell-enriched culture medium is sulfated glycoprotein-2 (SGP-2)","volume":"155","author":"Cheng","year":"1988","journal-title":"Biochem Biophys Res Commun"},{"key":"2022121212363933600_ref43","doi-asserted-by":"crossref","first-page":"1759","DOI":"10.1242\/dev.120.7.1759","article-title":"Developmental stage- and spermatogenic cycle-specific expression of transcription factor GATA-1 in mouse Sertoli cells","volume":"120","author":"Yomogida","year":"1994","journal-title":"Development"},{"key":"2022121212363933600_ref44","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1095\/biolreprod.110.086231","article-title":"Activin a balances Sertoli and germ cell proliferation in the fetal mouse testis","volume":"84","author":"Mendis","year":"2011","journal-title":"Biol Reprod"},{"key":"2022121212363933600_ref45","doi-asserted-by":"crossref","first-page":"10373","DOI":"10.1096\/fj.202000361R","article-title":"Ablation of the canonical testosterone production pathway via knockout of the steroidogenic enzyme HSD17B3, reveals a novel mechanism of testicular testosterone production","volume":"34","author":"Rebourcet","year":"2020","journal-title":"FASEB J"},{"key":"2022121212363933600_ref46","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1095\/biolreprod.115.129718","article-title":"CYP26 enzymes are necessary within the postnatal seminiferous epithelium for normal murine spermatogenesis","volume":"93","author":"Hogarth","year":"2015","journal-title":"Biol Reprod"},{"key":"2022121212363933600_ref47","doi-asserted-by":"crossref","first-page":"909","DOI":"10.1038\/35002622","article-title":"The LIM homeobox gene Lhx9 is essential for mouse gonad formation","volume":"403","author":"Birk","year":"2000","journal-title":"Nature"},{"key":"2022121212363933600_ref48","doi-asserted-by":"crossref","first-page":"2328","DOI":"10.1126\/science.286.5448.2328","article-title":"Postnatal sex reversal of the ovaries in mice lacking estrogen receptors alpha and beta","volume":"286","author":"Couse","year":"1999","journal-title":"Science"},{"key":"2022121212363933600_ref49","doi-asserted-by":"crossref","first-page":"115","DOI":"10.1016\/j.canlet.2004.10.007","article-title":"Cytochrome P450-mediated metabolism of estrogens and its regulation in human","volume":"227","author":"Tsuchiya","year":"2005","journal-title":"Cancer Lett"},{"key":"2022121212363933600_ref50","doi-asserted-by":"crossref","first-page":"3272","DOI":"10.1016\/j.celrep.2019.02.069","article-title":"Dissecting cell lineage specification and sex fate determination in gonadal somatic cells using single-cell transcriptomics","volume":"26","author":"Stevant","year":"2019","journal-title":"Cell Rep"},{"key":"2022121212363933600_ref51","doi-asserted-by":"crossref","first-page":"373","DOI":"10.1016\/S1567-133X(02)00050-9","article-title":"Lhx9 expression during gonadal morphogenesis as related to the state of cell differentiation","volume":"2","author":"Mazaud","year":"2002","journal-title":"Gene Expr Patterns"},{"key":"2022121212363933600_ref52","first-page":"1607","article-title":"Numb regulates somatic cell lineage commitment during early gonadogenesis in mice","volume":"144","author":"Lin","year":"2017","journal-title":"Development"},{"key":"2022121212363933600_ref53","doi-asserted-by":"crossref","first-page":"181","DOI":"10.1016\/S0074-7696(04)33005-6","article-title":"Cell biology of Leydig cells in the testis","volume":"233","author":"Haider","year":"2004","journal-title":"Int Rev Cytol"},{"key":"2022121212363933600_ref54","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/humupd\/dmi020","article-title":"Regulation of primordial follicle assembly and development","volume":"11","author":"Skinner","year":"2005","journal-title":"Hum Reprod Update"},{"key":"2022121212363933600_ref55","doi-asserted-by":"crossref","first-page":"483","DOI":"10.1097\/MED.0000000000000116","article-title":"5-alpha reductase deficiency: a 40-year retrospective review","volume":"21","author":"Okeigwe","year":"2014","journal-title":"Curr Opin Endocrinol Diabetes Obes"},{"key":"2022121212363933600_ref56","doi-asserted-by":"crossref","first-page":"3627","DOI":"10.1242\/dev.01239","article-title":"Fgf9 induces proliferation and nuclear localization of FGFR2 in Sertoli precursors during male sex determination","volume":"131","author":"Schmahl","year":"2004","journal-title":"Development"},{"key":"2022121212363933600_ref57","doi-asserted-by":"crossref","first-page":"10255","DOI":"10.1038\/ncomms10255","article-title":"mTORC1-independent raptor prevents hepatic steatosis by stabilizing PHLPP2","volume":"7","author":"Kim","year":"2016","journal-title":"Nat Commun"},{"key":"2022121212363933600_ref58","doi-asserted-by":"crossref","first-page":"416","DOI":"10.1038\/s41588-021-00825-y","article-title":"A resource of targeted mutant mouse lines for 5,061 genes","volume":"53","author":"Birling","year":"2021","journal-title":"Nat Genet"},{"key":"2022121212363933600_ref59","doi-asserted-by":"crossref","first-page":"769","DOI":"10.1530\/rep.0.1250769","article-title":"Proliferation and functional maturation of Sertoli cells, and their relevance to disorders of testis function in adulthood","volume":"125","author":"Sharpe","year":"2003","journal-title":"Reproduction"}],"container-title":["Biology of Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/biolreprod\/advance-article-pdf\/doi\/10.1093\/biolre\/ioac104\/44118824\/ioac104.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/107\/4\/1125\/47785593\/ioac104.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/biolreprod\/article-pdf\/107\/4\/1125\/47785593\/ioac104.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,12,12]],"date-time":"2022-12-12T12:37:40Z","timestamp":1670848660000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/biolreprod\/article\/107\/4\/1125\/6588711"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2022,5,19]]},"references-count":59,"journal-issue":{"issue":"4","published-online":{"date-parts":[[2022,5,19]]},"published-print":{"date-parts":[[2022,10,11]]}},"URL":"https:\/\/doi.org\/10.1093\/biolre\/ioac104","relation":{},"ISSN":["0006-3363","1529-7268"],"issn-type":[{"value":"0006-3363","type":"print"},{"value":"1529-7268","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2022,10]]},"published":{"date-parts":[[2022,5,19]]}}}