{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,8,21]],"date-time":"2025-08-21T17:28:13Z","timestamp":1755797293916,"version":"3.44.0"},"reference-count":35,"publisher":"Public Library of Science (PLoS)","issue":"8","license":[{"start":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T00:00:00Z","timestamp":1755475200000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001809","name":"Natural Science Foundation of China","doi-asserted-by":"crossref","award":["32302740"],"award-info":[{"award-number":["32302740"]}],"id":[{"id":"10.13039\/501100001809","id-type":"DOI","asserted-by":"crossref"}]},{"name":"Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions"}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS One"],"abstract":"<jats:p>Uterine glands and their secretions are essential for conceptus survival and development, with abnormalities in uterine gland morphogenesis (adenogenesis) are closely related to high rates of peri-implantation embryonic loss in humans and livestock. While uterine adenogenesis occurs postnatally in most mammals, the key regulatory factors and mechanisms governing this developmental event remains largely unexplored. Our recent study reveals that cysteine dioxygenase (CDO) is highly expressed in the uterus of adult mice, which is also rich in taurine. Notably, <jats:italic>Cdo<\/jats:italic> knockout (KO) and the resulting taurine deficiency lead to the defects in embryo implantation and subfertility. However, the regulatory roles of CDO and taurine in uterine development and adenogenesis remain unclear. In the current study, we assayed CDO expression and taurine content in the developmental uteri of mice from postnatal day (PND) 3 to PND 28, and investigated the regulatory roles of CDO and taurine in uterine adenogenesis using <jats:italic>Cdo<\/jats:italic> KO mice. Our results showed that uterine CDO protein expression gradually increased from PND 3 to prepuberty, closely correlating with uterine taurine levels. <jats:italic>Cdo<\/jats:italic> KO and taurine deficiency impaired the formation and development of uterine gland by inhibiting uterine epithelial cell proliferation and enhancing cell apoptosis. Remarkably, taurine supplementation partially rescued these defects in uterine adenogenesis. These findings, for the first time, demonstrate that uterine tissue acquires the ability to synthesis taurine postnatally, CDO and taurine act as novel factors regulating uterine gland development. Uncovering the mechanisms of uterine adenogenesis could significantly improve pregnancy outcomes in humans and other mammals.<\/jats:p>","DOI":"10.1371\/journal.pone.0329503","type":"journal-article","created":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T17:42:48Z","timestamp":1755538968000},"page":"e0329503","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":0,"title":["Cysteine dioxygenase knockout and taurine deficiency impair mouse uterine adenogenesis by inhibiting epithelial cell proliferation and enhancing apoptosis"],"prefix":"10.1371","volume":"20","author":[{"given":"Hui","family":"Liu","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuneng","family":"Gong","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaoyan","family":"Qu","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sheng","family":"Cui","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-1533-7186","authenticated-orcid":true,"given":"Di","family":"Zhang","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"340","published-online":{"date-parts":[[2025,8,18]]},"reference":[{"key":"pone.0329503.ref001","doi-asserted-by":"crossref","first-page":"81","DOI":"10.1093\/humrep\/15.suppl_1.81","article-title":"Uterine contractility during the menstrual cycle","volume":"15","author":"C Bulletti","year":"2000","journal-title":"Hum Reprod"},{"issue":"4","key":"pone.0329503.ref002","doi-asserted-by":"crossref","first-page":"531","DOI":"10.1007\/s00109-020-02028-0","article-title":"Organoids of the female reproductive tract","volume":"99","author":"C Chumduri","year":"2021","journal-title":"J Mol Med (Berl)"},{"issue":"1","key":"pone.0329503.ref003","doi-asserted-by":"crossref","first-page":"21","DOI":"10.1002\/aja.1001860103","article-title":"Histologic, morphometric, and immunocytochemical analysis of myometrial development in rats and mice: II. Effects of DES on development","volume":"186","author":"JR Brody","year":"1989","journal-title":"Am J Anat"},{"key":"pone.0329503.ref004","doi-asserted-by":"crossref","first-page":"85","DOI":"10.1016\/S0070-2153(05)68004-0","article-title":"Comparative developmental biology of the mammalian uterus","volume":"68","author":"TE Spencer","year":"2005","journal-title":"Curr Top Dev Biol"},{"issue":"5","key":"pone.0329503.ref005","doi-asserted-by":"crossref","first-page":"346","DOI":"10.1055\/s-0034-1376354","article-title":"Biological roles of uterine glands in pregnancy","volume":"32","author":"TE Spencer","year":"2014","journal-title":"Semin Reprod Med"},{"issue":"4","key":"pone.0329503.ref006","doi-asserted-by":"crossref","first-page":"93","DOI":"10.1095\/biolreprod.113.107631","article-title":"Endometrial glands are essential for blastocyst implantation and decidualization in the mouse uterus","volume":"88","author":"J Filant","year":"2013","journal-title":"Biol Reprod"},{"key":"pone.0329503.ref007","doi-asserted-by":"crossref","first-page":"125","DOI":"10.1146\/annurev-animal-020518-115321","article-title":"Development and function of uterine glands in domestic animals","volume":"7","author":"TE Spencer","year":"2019","journal-title":"Annu Rev Anim Biosci"},{"issue":"2","key":"pone.0329503.ref008","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1016\/j.ydbio.2007.03.027","article-title":"Cellular mechanisms of Mullerian duct formation in the mouse","volume":"306","author":"GD Orvis","year":"2007","journal-title":"Dev Biol"},{"issue":"9","key":"pone.0329503.ref009","doi-asserted-by":"crossref","first-page":"1442","DOI":"10.1210\/me.2012-1126","article-title":"CTNNB1 in mesenchyme regulates epithelial cell differentiation during Mullerian duct and postnatal uterine development","volume":"27","author":"CA Stewart","year":"2013","journal-title":"Mol Endocrinol"},{"issue":"12","key":"pone.0329503.ref010","doi-asserted-by":"crossref","first-page":"969","DOI":"10.1038\/nrg1225","article-title":"Developmental genetics of the female reproductive tract in mammals","volume":"4","author":"A Kobayashi","year":"2003","journal-title":"Nat Rev Genet"},{"issue":"3","key":"pone.0329503.ref011","doi-asserted-by":"crossref","first-page":"396","DOI":"10.1095\/biolreprod.109.083154","article-title":"Foxa2 is essential for mouse endometrial gland development and fertility","volume":"83","author":"J-W Jeong","year":"2010","journal-title":"Biol Reprod"},{"issue":"12","key":"pone.0329503.ref012","doi-asserted-by":"crossref","first-page":"2013","DOI":"10.1038\/cdd.2017.120","article-title":"PR-Set7 deficiency limits uterine epithelial population growth hampering postnatal gland formation in mice","volume":"24","author":"T Cui","year":"2017","journal-title":"Cell Death Differ"},{"issue":"1","key":"pone.0329503.ref013","doi-asserted-by":"crossref","first-page":"58","DOI":"10.1016\/j.ydbio.2016.11.023","article-title":"Porcupine-dependent Wnt signaling controls stromal proliferation and endometrial gland maintenance through the action of distinct WNTs","volume":"422","author":"O Farah","year":"2017","journal-title":"Dev Biol"},{"issue":"1","key":"pone.0329503.ref014","doi-asserted-by":"crossref","first-page":"5378","DOI":"10.1038\/s41467-019-13363-3","article-title":"Neonatal Wnt-dependent Lgr5 positive stem cells are essential for uterine gland development","volume":"10","author":"R Seishima","year":"2019","journal-title":"Nat Commun"},{"issue":"1","key":"pone.0329503.ref015","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.stem.2019.11.012","article-title":"Endometrial Axin2( ) cells drive epithelial homeostasis, regeneration, and cancer following oncogenic transformation","volume":"26","author":"SM Syed","year":"2020","journal-title":"Cell Stem Cell"},{"issue":"1","key":"pone.0329503.ref016","doi-asserted-by":"crossref","first-page":"97","DOI":"10.1093\/hmg\/ddv452","article-title":"Dlx5 and Dlx6 control uterine adenogenesis during post-natal maturation: possible consequences for endometriosis","volume":"25","author":"B Bellessort","year":"2016","journal-title":"Hum Mol Genet"},{"issue":"6","key":"pone.0329503.ref017","doi-asserted-by":"crossref","DOI":"10.1073\/pnas.1618433114","article-title":"Forkhead box a2 (FOXA2) is essential for uterine function and fertility","volume":"114","author":"AM Kelleher","year":"2017","journal-title":"Proc Natl Acad Sci U S A"},{"key":"pone.0329503.ref018","doi-asserted-by":"crossref","first-page":"273","DOI":"10.1111\/j.1439-0531.2008.01174.x","article-title":"Epigenetic programming of porcine endometrial function and the lactocrine hypothesis","author":"FF Bartol","year":"2008","journal-title":"Reprod Domest Anim"},{"issue":"1","key":"pone.0329503.ref019","doi-asserted-by":"crossref","first-page":"110","DOI":"10.1210\/en.2002-220627","article-title":"Prolactin regulation of neonatal ovine uterine gland morphogenesis","volume":"144","author":"KD Carpenter","year":"2003","journal-title":"Endocrinology"},{"issue":"1","key":"pone.0329503.ref020","doi-asserted-by":"crossref","first-page":"67","DOI":"10.1002\/1098-2795(200009)57:1<67::AID-MRD10>3.0.CO;2-M","article-title":"Mechanisms regulating norgestomet inhibition of endometrial gland morphogenesis in the neonatal ovine uterus","volume":"57","author":"CA Gray","year":"2000","journal-title":"Mol Reprod Dev"},{"issue":"7","key":"pone.0329503.ref021","first-page":"903","article-title":"Effects of an Igf1 gene null mutation on mouse reproduction","volume":"10","author":"J Baker","year":"1996","journal-title":"Mol Endocrinol"},{"issue":"4","key":"pone.0329503.ref022","doi-asserted-by":"crossref","first-page":"1236","DOI":"10.1095\/biolreprod64.4.1236","article-title":"Expression of messenger ribonucleic acids for fibroblast growth factors 7 and 10, hepatocyte growth factor, and insulin-like growth factors and their receptors in the neonatal ovine uterus","volume":"64","author":"KM Taylor","year":"2001","journal-title":"Biol Reprod"},{"issue":"6","key":"pone.0329503.ref023","doi-asserted-by":"crossref","first-page":"2520","DOI":"10.1210\/endo-117-6-2520","article-title":"Effects of progestins and glucocorticoids on deoxyribonucleic acid synthesis in the uterus of the neonatal mouse","volume":"117","author":"RM Bigsby","year":"1985","journal-title":"Endocrinology"},{"issue":"2","key":"pone.0329503.ref024","article-title":"Taurine is Involved in Energy Metabolism in Muscles, Adipose Tissue, and the Liver","volume":"63","author":"C Wen","year":"2019","journal-title":"Mol Nutr Food Res"},{"issue":"1","key":"pone.0329503.ref025","doi-asserted-by":"crossref","first-page":"191","DOI":"10.1111\/apha.12365","article-title":"Physiological role of taurine--from organism to organelle","volume":"213","author":"IH Lambert","year":"2015","journal-title":"Acta Physiol (Oxf)"},{"issue":"4","key":"pone.0329503.ref026","doi-asserted-by":"crossref","first-page":"595","DOI":"10.1016\/S0168-8278(98)80155-4","article-title":"Hepatic localisation of rat cysteine dioxygenase","volume":"29","author":"RB Parsons","year":"1998","journal-title":"J Hepatol"},{"issue":"1","key":"pone.0329503.ref027","doi-asserted-by":"crossref","first-page":"17","DOI":"10.1007\/s10545-009-9006-9","article-title":"Dealing with methionine\/homocysteine sulfur: cysteine metabolism to taurine and inorganic sulfur","volume":"34","author":"MH Stipanuk","year":"2011","journal-title":"J Inherit Metab Dis"},{"issue":"4","key":"pone.0329503.ref028","doi-asserted-by":"crossref","DOI":"10.1152\/ajpendo.00151.2011","article-title":"Knockout of the murine cysteine dioxygenase gene results in severe impairment in ability to synthesize taurine and an increased catabolism of cysteine to hydrogen sulfide","volume":"301","author":"I Ueki","year":"2011","journal-title":"Am J Physiol Endocrinol Metab"},{"issue":"1","key":"pone.0329503.ref029","doi-asserted-by":"crossref","first-page":"6","DOI":"10.1186\/s40104-022-00804-1","article-title":"Cysteine dioxygenase and taurine are essential for embryo implantation by involving in E2-ER\u03b1 and P4-PR signaling in mouse","volume":"14","author":"D Zhang","year":"2023","journal-title":"J Anim Sci Biotechnol"},{"key":"pone.0329503.ref030","doi-asserted-by":"crossref","first-page":"38078","DOI":"10.1038\/srep38078","article-title":"Uterine glands impact uterine receptivity, luminal fluid homeostasis and blastocyst implantation","volume":"6","author":"AM Kelleher","year":"2016","journal-title":"Sci Rep"},{"key":"pone.0329503.ref031","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1016\/bs.ctdb.2021.12.004","article-title":"Mammalian uterine morphogenesis and variations","volume":"148","author":"DA Machado","year":"2022","journal-title":"Curr Top Dev Biol"},{"issue":"5","key":"pone.0329503.ref032","doi-asserted-by":"crossref","first-page":"1424","DOI":"10.1210\/er.2018-00281","article-title":"Uterine Glands: Developmental Biology and Functional Roles in Pregnancy","volume":"40","author":"AM Kelleher","year":"2019","journal-title":"Endocr Rev"},{"issue":"12","key":"pone.0329503.ref033","doi-asserted-by":"crossref","first-page":"1001","DOI":"10.1038\/nrd2637","article-title":"Directing cancer cells to self-destruct with pro-apoptotic receptor agonists","volume":"7","author":"A Ashkenazi","year":"2008","journal-title":"Nat Rev Drug Discov"},{"issue":"5","key":"pone.0329503.ref034","doi-asserted-by":"crossref","first-page":"379","DOI":"10.1038\/s41580-023-00689-6","article-title":"A guide to cell death pathways","volume":"25","author":"J Yuan","year":"2024","journal-title":"Nat Rev Mol Cell Biol"},{"issue":"1","key":"pone.0329503.ref035","doi-asserted-by":"crossref","first-page":"11","DOI":"10.1016\/S1534-5807(02)00410-0","article-title":"Tube or not tube: remodeling epithelial tissues by branching morphogenesis","volume":"4","author":"M Affolter","year":"2003","journal-title":"Dev Cell"}],"container-title":["PLOS One"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0329503","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,8,18]],"date-time":"2025-08-18T17:42:56Z","timestamp":1755538976000},"score":1,"resource":{"primary":{"URL":"https:\/\/dx.plos.org\/10.1371\/journal.pone.0329503"}},"subtitle":[],"editor":[{"given":"Jin Su","family":"Kim","sequence":"first","affiliation":[],"role":[{"role":"editor","vocabulary":"crossref"}]}],"short-title":[],"issued":{"date-parts":[[2025,8,18]]},"references-count":35,"journal-issue":{"issue":"8","published-online":{"date-parts":[[2025,8,18]]}},"URL":"https:\/\/doi.org\/10.1371\/journal.pone.0329503","relation":{},"ISSN":["1932-6203"],"issn-type":[{"type":"electronic","value":"1932-6203"}],"subject":[],"published":{"date-parts":[[2025,8,18]]}}}