{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T05:05:13Z","timestamp":1771218313702,"version":"3.50.1"},"reference-count":43,"publisher":"Oxford University Press (OUP)","issue":"2","license":[{"start":{"date-parts":[[2026,1,23]],"date-time":"2026-01-23T00:00:00Z","timestamp":1769126400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/academic.oup.com\/pages\/standard-publication-reuse-rights"}],"funder":[{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R03HD097384"],"award-info":[{"award-number":["R03HD097384"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R03HD100652"],"award-info":[{"award-number":["R03HD100652"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100000002","name":"NIH","doi-asserted-by":"publisher","award":["R01HD114750"],"award-info":[{"award-number":["R01HD114750"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,2,5]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Uterine epithelial estrogen receptor \u03b1 (ER\u03b1) deficiency in epiER\u03b1-\/- (Esr1f\/-Wnt7aCre\/+) mice leads to dysregulated environment of uterine lumen, which is lined by uterine luminal epithelium (LE). We hypothesized that transcriptomes in the LE layer held molecular keys to understanding ER\u03b1 in regulating preimplantation uterine environment. Day 0.5 post-coitum (D0.5) and D3.5 LE layer (isolated via enzymatic digestion), digested uterus (DU), and uterus (U) from Esr1f\/- (control) and epiER\u03b1-\/- mice were processed for mRNA-seq. There were minimal differentially expressed genes (DEGs: transcripts per million\u2009&amp;gt;\u20091, fold-change\u2009&amp;gt;\u20092, false discovery rate\u2009&amp;lt;\u20090.05) between DU and U. Between D0.5 and D3.5 Esr1f\/- LE layer, the top upregulated and downregulated gene ontology biological process (GOBP) pathways were on cellular processes and innate immune responses, respectively. Compared to Esr1f\/- LE layer, the most upregulated and downregulated pathways in D0.5 epiER\u03b1-\/- LE layer were on innate immune responses and on biosynthesis and metabolism, respectively; while those in D3.5 epiER\u03b1-\/- LE layer were on cell division and on signaling and metabolic processes, respectively. Na+ transmembrane transport was among shared upregulated pathways in D0.5 and D3.5 epiER\u03b1-\/- LE layer. Between Esr1f\/- and epiER\u03b1-\/-, most DEGs in U were also DEGs in the LE layer, and limited DEGs in U only with higher expression than in the LE layer were related to immune responses, implying potential paracrine effects of uterine epithelial ER\u03b1. Selected DEGs were verified by realtime PCR and immunohistochemistry. This mRNA-seq dataset provides molecular keys to understanding temporal (e.g., innate immunity) and constituent (e.g., uterine fluid movement) functions, and potential paracrine effects of uterine epithelial ER\u03b1 in regulating the preimplantation uterine environment.<\/jats:p>","DOI":"10.1093\/reprod\/xaaf025","type":"journal-article","created":{"date-parts":[[2026,1,5]],"date-time":"2026-01-05T12:23:41Z","timestamp":1767615821000},"source":"Crossref","is-referenced-by-count":0,"title":["Uterine epithelial ER\u03b1 regulates preimplantation uterine luminal epithelial and uterine mRNAs"],"prefix":"10.1093","volume":"171","author":[{"given":"Jonathan Matthew","family":"Hancock","sequence":"first","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia , Athens, GA,","place":["United States"]},{"name":"Interdisciplinary Toxicology Program, University of Georgia , Athens, GA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-2361-1931","authenticated-orcid":false,"given":"Tong","family":"Zhou","sequence":"additional","affiliation":[{"name":"Department of Physiology and Cell Biology, University of Nevada, Reno School of Medicine , Reno, NV,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yuehuan","family":"Li","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia , Athens, GA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Taylor Elijah","family":"Martin","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia , Athens, GA,","place":["United States"]},{"name":"Interdisciplinary Toxicology Program, University of Georgia , Athens, GA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Moya","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia , Athens, GA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1037-9005","authenticated-orcid":false,"given":"Xiaoqin","family":"Ye","sequence":"additional","affiliation":[{"name":"Department of Physiology and Pharmacology, College of Veterinary Medicine, University of Georgia , Athens, GA,","place":["United States"]},{"name":"Interdisciplinary Toxicology Program, University of Georgia , Athens, GA,","place":["United States"]}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"286","published-online":{"date-parts":[[2026,1,23]]},"reference":[{"key":"2026021523214749600_xaaf025-B1","doi-asserted-by":"publisher","first-page":"821","DOI":"10.1016\/j.cell.2023.01.016","article-title":"Structures of LRP2 reveal a molecular machine for endocytosis","volume":"186","author":"Beenken","year":"2023","journal-title":"Cell"},{"key":"2026021523214749600_xaaf025-B2","doi-asserted-by":"publisher","first-page":"390","DOI":"10.1210\/endo-119-1-390","article-title":"Estrogen stimulation of deoxyribonucleic acid synthesis in uterine epithelial cells which lack estrogen receptors","volume":"119","author":"Bigsby","year":"1986","journal-title":"Endocrinology"},{"key":"2026021523214749600_xaaf025-B3","doi-asserted-by":"publisher","first-page":"525","DOI":"10.1038\/nbt.3519","article-title":"Near-optimal probabilistic RNA-seq quantification","volume":"34","author":"Bray","year":"2016","journal-title":"Nature Biotechnology"},{"key":"2026021523214749600_xaaf025-B4","doi-asserted-by":"publisher","first-page":"4872","DOI":"10.1091\/mbc.e07-06-0563","article-title":"Antibody to AP1B adaptor blocks biosynthetic and recycling routes of basolateral proteins at recycling endosomes","volume":"18","author":"Cancino","year":"2007","journal-title":"Molecular Biology of the Cell"},{"key":"2026021523214749600_xaaf025-B5","doi-asserted-by":"publisher","first-page":"6535","DOI":"10.1073\/pnas.94.12.6535","article-title":"Stromal estrogen receptors mediate mitogenic effects of estradiol on uterine epithelium","volume":"94","author":"Cooke","year":"1997","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"2026021523214749600_xaaf025-B6","doi-asserted-by":"publisher","first-page":"123","DOI":"10.1095\/biolreprod.115.131110","article-title":"Deletion of lysophosphatidic acid receptor 3 (Lpar3) disrupts fine local balance of progesterone and estrogen signaling in mouse uterus during implantation","volume":"93","author":"Diao","year":"2015","journal-title":"Biology of Reproduction"},{"key":"2026021523214749600_xaaf025-B7","doi-asserted-by":"publisher","first-page":"2750","DOI":"10.1016\/j.fertnstert.2010.01.009","article-title":"Progesterone receptor-mediated up-regulation of transthyretin in preimplantation mouse uterus","volume":"93","author":"Diao","year":"2010","journal-title":"Fertility and Sterility"},{"key":"2026021523214749600_xaaf025-B8","doi-asserted-by":"publisher","first-page":"31","DOI":"10.1095\/biolreprod.113.110106","article-title":"Broad gap junction blocker carbenoxolone disrupts uterine preparation for embryo implantation in mice","volume":"89","author":"Diao","year":"2013","journal-title":"Biology of Reproduction"},{"key":"2026021523214749600_xaaf025-B9","doi-asserted-by":"publisher","first-page":"2808","DOI":"10.1016\/j.fertnstert.2010.06.034","article-title":"Uterine luminal epithelium-specific proline-rich acidic protein 1 (PRAP1) as a marker for successful embryo implantation","volume":"94","author":"Diao","year":"2010","journal-title":"Fertility and Sterility"},{"key":"2026021523214749600_xaaf025-B10","doi-asserted-by":"publisher","first-page":"1218","DOI":"10.1096\/fj.11-193334","article-title":"Epithelial progesterone receptor exhibits pleiotropic roles in uterine development and function","volume":"26","author":"Franco","year":"2012","journal-title":"FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology"},{"key":"2026021523214749600_xaaf025-B11","doi-asserted-by":"publisher","first-page":"12293","DOI":"10.1038\/s41598-023-39474-y","article-title":"The role of mesenchymal estrogen receptor 1 in mouse uterus in response to estrogen","volume":"13","author":"Furuminato","year":"2023","journal-title":"Scientific Reports"},{"key":"2026021523214749600_xaaf025-B12","doi-asserted-by":"publisher","DOI":"10.1093\/molehr\/gaae020","article-title":"Murine uterine gland branching is necessary for gland function in implantation","volume":"30","author":"Granger","year":"2024","journal-title":"Molecular Human Reproduction"},{"key":"2026021523214749600_xaaf025-B13","doi-asserted-by":"publisher","first-page":"359","DOI":"10.1093\/biolre\/ioac225","article-title":"Upregulation of FOXA2 in uterine luminal epithelium and vaginal basal epithelium of epiERalpha-\/- (Esr1fl\/flWnt7aCre\/+) micedagger","volume":"108","author":"Hancock","year":"2023","journal-title":"Biology of Reproduction"},{"key":"2026021523214749600_xaaf025-B14","doi-asserted-by":"publisher","DOI":"10.1530\/REP-24-0447","article-title":"Increased plugging latency in cycling epiERalpha -\/- (Esr1 f\/- Wnt7a Cre\/+) mice","volume":"169","author":"Hancock","year":"2025","journal-title":"Reproduction (Cambridge, England)"},{"key":"2026021523214749600_xaaf025-B15","doi-asserted-by":"publisher","first-page":"4660","DOI":"10.1096\/fj.10-163428","article-title":"Biological and biochemical consequences of global deletion of exon 3 from the ER alpha gene","volume":"24","author":"Hewitt","year":"2010","journal-title":"FASEB Journal: Official Publication of the Federation of American Societies for Experimental Biology"},{"key":"2026021523214749600_xaaf025-B16","doi-asserted-by":"publisher","first-page":"664","DOI":"10.1210\/er.2018-00087","article-title":"Estrogen receptors: New directions in the new millennium","volume":"39","author":"Hewitt","year":"2018","journal-title":"Endocrine Reviews"},{"key":"2026021523214749600_xaaf025-B17","doi-asserted-by":"publisher","first-page":"887","DOI":"10.1210\/me.2011-1311","article-title":"Research resource: whole-genome estrogen receptor alpha binding in mouse uterine tissue revealed by ChIP-seq","volume":"26","author":"Hewitt","year":"2012","journal-title":"Molecular Endocrinology (Baltimore, Md.)"},{"key":"2026021523214749600_xaaf025-B18","doi-asserted-by":"publisher","first-page":"307","DOI":"10.1089\/vim.2019.0144","article-title":"From influenza virus infections to lupus: Synchronous estrogen receptor alpha and RNA polymerase II binding within the immunoglobulin heavy chain locus","volume":"33","author":"Jones","year":"2020","journal-title":"Viral Immunology"},{"key":"2026021523214749600_xaaf025-B19","doi-asserted-by":"publisher","first-page":"1204","DOI":"10.1038\/ng1874","article-title":"Indian hedgehog is a major mediator of progesterone signaling in the mouse uterus","volume":"38","author":"Lee","year":"2006","journal-title":"Nature Genetics"},{"key":"2026021523214749600_xaaf025-B20","doi-asserted-by":"publisher","first-page":"e1006743","DOI":"10.1371\/journal.pgen.1006743","article-title":"Crucial role of estrogen for the mammalian female in regulating semen coagulation and liquefaction in vivo","volume":"13","author":"Li","year":"2017","journal-title":"PLoS Genetics"},{"key":"2026021523214749600_xaaf025-B21","doi-asserted-by":"publisher","DOI":"10.1210\/endocr\/bqaa050","article-title":"ESR1 mutations associated with estrogen insensitivity syndrome change conformation of ligand-receptor complex and altered transcriptome profile","volume":"161","author":"Li","year":"2020","journal-title":"Endocrinology"},{"key":"2026021523214749600_xaaf025-B22","doi-asserted-by":"publisher","first-page":"204","DOI":"10.1093\/biolre\/ioac198","article-title":"Visualization of preimplantation uterine fluid absorption in mice using Alexa Fluor 488 Hydrazidedagger","volume":"108","author":"Li","year":"2023","journal-title":"Biology of Reproduction"},{"key":"2026021523214749600_xaaf025-B23","doi-asserted-by":"publisher","first-page":"100077","DOI":"10.1016\/j.waojou.2019.100077","article-title":"Calcium-activated chloride channel regulator 1 (CLCA1): More than a regulator of chloride transport and mucus production","volume":"12","author":"Liu","year":"2019","journal-title":"The World Allergy Organization Journal"},{"key":"2026021523214749600_xaaf025-B24","doi-asserted-by":"publisher","first-page":"3201","DOI":"10.1242\/dev.125.16.3201","article-title":"Wnt-7a maintains appropriate uterine patterning during the development of the mouse \u00adfemale reproductive tract","volume":"125","author":"Miller","year":"1998","journal-title":"Development (Cambridge, England)"},{"key":"2026021523214749600_xaaf025-B25","doi-asserted-by":"publisher","first-page":"175","DOI":"10.1016\/j.bbrc.2013.10.037","article-title":"Progesterone induces expression of Lrp2 in the murine uterus","volume":"441","author":"Oh","year":"2013","journal-title":"Biochemical and Biophysical Research Communications"},{"key":"2026021523214749600_xaaf025-B26","doi-asserted-by":"publisher","first-page":"3958","DOI":"10.1210\/endo.139.9.6173","article-title":"Histidine decarboxylase gene in the mouse uterus is regulated by progesterone and correlates with uterine differentiation for blastocyst implantation","volume":"139","author":"Paria","year":"1998","journal-title":"Endocrinology"},{"key":"2026021523214749600_xaaf025-B27","doi-asserted-by":"publisher","first-page":"1362","DOI":"10.1210\/me.2015-1142","article-title":"Uterine epithelial estrogen receptor-alpha controls decidualization via a paracrine mechanism","volume":"29","author":"Pawar","year":"2015","journal-title":"Molecular Endocrinology (Baltimore, Md.)"},{"key":"2026021523214749600_xaaf025-B28","doi-asserted-by":"publisher","first-page":"107568","DOI":"10.1016\/j.isci.2023.107568","article-title":"Estrogen receptor alpha regulates uterine epithelial lineage specification and homeostasis","volume":"26","author":"Rizo","year":"2023","journal-title":"iScience"},{"key":"2026021523214749600_xaaf025-B29","doi-asserted-by":"publisher","first-page":"139","DOI":"10.1093\/bioinformatics\/btp616","article-title":"edgeR: A Bioconductor package for differential expression analysis of digital gene expression data","volume":"26","author":"Robinson","year":"2010","journal-title":"Bioinformatics (Oxford, England)"},{"key":"2026021523214749600_xaaf025-B30","doi-asserted-by":"publisher","first-page":"W216","DOI":"10.1093\/nar\/gkac194","article-title":"DAVID: A web server for functional enrichment analysis and functional annotation of gene lists (2021 update)","volume":"50","author":"Sherman","year":"2022","journal-title":"Nucleic Acids Research"},{"key":"2026021523214749600_xaaf025-B31","doi-asserted-by":"publisher","first-page":"5310","DOI":"10.1210\/endo.140.11.7148","article-title":"Differential \u00aduterine expression of estrogen and progesterone receptors \u00adcorrelates with uterine preparation for implantation and decidualization in the mouse","volume":"140","author":"Tan","year":"1999","journal-title":"Endocrinology"},{"key":"2026021523214749600_xaaf025-B32","doi-asserted-by":"publisher","first-page":"4057","DOI":"10.1242\/dev.121.12.4057","article-title":"Pax-2 controls multiple steps of urogenital development","volume":"121","author":"Torres","year":"1995","journal-title":"Development (Cambridge, England)"},{"key":"2026021523214749600_xaaf025-B33","doi-asserted-by":"publisher","first-page":"120","DOI":"10.1002\/aja.1001820203","article-title":"Endocytosis in the uterine luminal and glandular epithelial cells of mice during early pregnancy","volume":"182","author":"Tung","year":"1988","journal-title":"The American Journal of Anatomy"},{"key":"2026021523214749600_xaaf025-B34","doi-asserted-by":"publisher","first-page":"e10453","DOI":"10.7554\/eLife.10453","article-title":"Oviductal estrogen receptor alpha signaling prevents protease-mediated embryo death","volume":"4","author":"Winuthayanon","year":"2015","journal-title":"eLife"},{"key":"2026021523214749600_xaaf025-B35","doi-asserted-by":"publisher","first-page":"110","DOI":"10.1095\/biolreprod.114.120170","article-title":"Uterine epithelial cell estrogen receptor alpha-dependent and -independent genomic profiles that underlie estrogen responses in mice","volume":"91","author":"Winuthayanon","year":"2014","journal-title":"Biology of Reproduction"},{"key":"2026021523214749600_xaaf025-B36","doi-asserted-by":"publisher","first-page":"19272","DOI":"10.1073\/pnas.1013226107","article-title":"Uterine epithelial estrogen receptor alpha is dispensable for proliferation but essential for complete biological and biochemical responses","volume":"107","author":"Winuthayanon","year":"2010","journal-title":"Proceedings of the National Academy of Sciences of the United States of America"},{"key":"2026021523214749600_xaaf025-B37","doi-asserted-by":"publisher","first-page":"351","DOI":"10.1177\/1933719113497287","article-title":"Differential gene expression profiling of mouse uterine \u00adluminal epithelium during periimplantation","volume":"21","author":"Xiao","year":"2014","journal-title":"Reproductive Sciences (Thousand Oaks, Calif.)"},{"key":"2026021523214749600_xaaf025-B38","doi-asserted-by":"publisher","first-page":"e65607","DOI":"10.1371\/journal.pone.0065607","article-title":"Progesterone receptor-mediated regulation of N-acetylneuraminate pyruvate lyase (NPL) in mouse uterine luminal epithelium and nonessential role of NPL in uterine function","volume":"8","author":"Xiao","year":"2013","journal-title":"PLoS One"},{"key":"2026021523214749600_xaaf025-B39","doi-asserted-by":"publisher","first-page":"232","DOI":"10.1095\/biolreprod.116.144451","article-title":"Acidification of uterine epithelium during embryo implantation in mice","volume":"96","author":"Xiao","year":"2017","journal-title":"Biology of Reproduction"},{"key":"2026021523214749600_xaaf025-B40","doi-asserted-by":"publisher","first-page":"165","DOI":"10.1016\/j.tem.2019.11.008","article-title":"Uterine luminal epithelium as the transient gateway for embryo implantation","volume":"31","author":"Ye","year":"2020","journal-title":"Trends in Endocrinology and Metabolism: TEM"},{"key":"2026021523214749600_xaaf025-B41","doi-asserted-by":"publisher","first-page":"104","DOI":"10.1038\/nature03505","article-title":"LPA3-mediated lysophosphatidic acid signalling in embryo implantation and spacing","volume":"435","author":"Ye","year":"2005","journal-title":"Nature"},{"key":"2026021523214749600_xaaf025-B42","doi-asserted-by":"publisher","first-page":"2107","DOI":"10.1016\/j.fertnstert.2011.02.024","article-title":"Unique uterine localization and regulation may differentiate LPA3 from other lysophospholipid receptors for its role in embryo implantation","volume":"95","author":"Ye","year":"2011","journal-title":"Fertility and Sterility"},{"key":"2026021523214749600_xaaf025-B43","doi-asserted-by":"publisher","first-page":"39","DOI":"10.1083\/jcb.117.1.39","article-title":"Cytoplasmic sequence required for basolateral targeting of LDL receptor in livers of transgenic mice","volume":"117","author":"Yokode","year":"1992","journal-title":"The Journal of Cell Biology"}],"container-title":["Reproduction"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/academic.oup.com\/reproduction\/advance-article-pdf\/doi\/10.1093\/reprod\/xaaf025\/66564292\/xaaf025.pdf","content-type":"application\/pdf","content-version":"am","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/171\/2\/xaaf025\/66564292\/xaaf025.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"syndication"},{"URL":"https:\/\/academic.oup.com\/reproduction\/article-pdf\/171\/2\/xaaf025\/66564292\/xaaf025.pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,2,16]],"date-time":"2026-02-16T04:22:04Z","timestamp":1771215724000},"score":1,"resource":{"primary":{"URL":"https:\/\/academic.oup.com\/reproduction\/article\/doi\/10.1093\/reprod\/xaaf025\/8440087"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,1,23]]},"references-count":43,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2026,2,5]]}},"URL":"https:\/\/doi.org\/10.1093\/reprod\/xaaf025","relation":{},"ISSN":["1741-7899"],"issn-type":[{"value":"1741-7899","type":"electronic"}],"subject":[],"published-other":{"date-parts":[[2026,2]]},"published":{"date-parts":[[2026,1,23]]},"article-number":"xaaf025"}}