{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,27]],"date-time":"2026-09-27T07:09:29Z","timestamp":1790492969034,"version":"4.1.0"},"reference-count":29,"publisher":"MDPI AG","issue":"24","license":[{"start":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T00:00:00Z","timestamp":1765152000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100002641","name":"Konkuk University","doi-asserted-by":"crossref","id":[{"id":"10.13039\/501100002641","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>In mice, the uterus undergoes dynamic changes regulated by estrogen and progesterone during the estrous cycle. Proper regulation of these changes is critical for successful pregnancy. The Family with sequence similarity 3 (Fam3) gene family, comprising Fam3a, Fam3b, Fam3c, and Fam3d, encodes cytokine-like proteins, but their uterine roles remain unclear. This study examined Fam3 expression in the mouse uterus across the estrous cycle and assessed estrogen-dependent regulation. RNA-seq analysis revealed increased Fam3b, Fam3c, and Fam3d expression during proestrus and estrus. Notably, Fam3d showed dynamic regulation, peaking in these stages. To test estrogen regulation, estradiol was administered to ovariectomized mice, showing maximal Fam3d expression at 24 h post-injection. ER\u03b1 antagonist treatment blocked this induction, indicating ER\u03b1-mediated regulation. Immunofluorescence localized FAM3D to the cytoplasm of luminal and glandular epithelia, especially in the apical region, with no stromal or nuclear expression. These findings suggest that estrogen and Er\u03b1 (Estrogen receptor alpha) signaling control Fam3d expression, implicating FAM3D in uterine epithelial function. This study provides novel insights into Fam3d\u2019s role in uterine physiology and a foundation for exploring its function in reproduction.<\/jats:p>","DOI":"10.3390\/ijms262411840","type":"journal-article","created":{"date-parts":[[2025,12,8]],"date-time":"2025-12-08T14:52:24Z","timestamp":1765205544000},"page":"11840","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":4,"title":["Estrogen-Mediated Regulation of Fam3d in Mouse Uterus During the Estrous Cycle"],"prefix":"10.3390","volume":"26","author":[{"given":"Hyukjung","family":"Kim","sequence":"first","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-4037-9222","authenticated-orcid":false,"given":"Byeongseok","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0502-1124","authenticated-orcid":false,"given":"Joohee","family":"Kim","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yeonju","family":"Suh","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jimin","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sangok","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Stem Cell and Regenerative Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Man Ryul","family":"Lee","sequence":"additional","affiliation":[{"name":"Major in Stem Cell and Regenerative Biotechnology, School of Advanced Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"},{"name":"The Institute of Advanced Regenerative Sciences, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6436-8918","authenticated-orcid":false,"given":"Hoi Chang","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Obstetrics and Gynecology, Feinberg School of Medicine, Northwestern University, Chicago, IL 60611, USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3862-4105","authenticated-orcid":false,"given":"Youngsok","family":"Choi","sequence":"additional","affiliation":[{"name":"Major in Stem Cell and Regenerative Biotechnology, School of Advanced Biotechnology, Konkuk University, Seoul 05029, Republic of Korea"},{"name":"The Institute of Advanced Regenerative Sciences, Konkuk University, Seoul 05029, Republic of Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2025,12,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"225","DOI":"10.5483\/BMBRep.2018.51.5.045","article-title":"Role of estrogen and RAS signaling in repeated implantation failure","volume":"51","author":"Hong","year":"2018","journal-title":"BMB Rep."},{"key":"ref_2","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":"Kobayashi","year":"2003","journal-title":"Nat. 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