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It is also implicated in adenocarcinoma and endometriosis. Little is known about this process in normal uterine physiology. Previously, using pregnancy and menses-like mouse models, MET occurred only as an epithelial damage\/repair mechanism. Here, we hypothesized that MET also occurs in other physiological endometrial remodeling events, outside of damage\/repair, such as during the estrous cycle and adenogenesis (gland development). To investigate this, <jats:italic>Amhr2-Cre-YFP\/GFP<\/jats:italic> mesenchyme-specific reporter mice were used to track the fate of mesenchymal-derived (MD) cells. Using EpCAM (epithelial marker), EpCAM<jats:sup>+<\/jats:sup>YFP<jats:sup>+<\/jats:sup> MD-epithelial cells were identified in all stages of the estrous cycle except diestrus, in both postpartum and virgin mice. EpCAM<jats:sup>+<\/jats:sup>YFP<jats:sup>+<\/jats:sup> MD-epithelial cells comprised up to 80% of the epithelia during estrogen-dominant proestrus and significantly declined to indistinguishable from control uteri in diestrus, suggesting MET is hormonally regulated. MD-epithelial cells were also identified during postnatal epithelial remodeling. MET occurred immediately after birth at postnatal day (P) 0.5 with EpCAM<jats:sup>+<\/jats:sup>GFP<jats:sup>+<\/jats:sup> cells ranging from negligible (0.21%) to 82% of the epithelia. EpCAM<jats:sup>+<\/jats:sup>GFP<jats:sup>+<\/jats:sup> MD-epithelial cells declined during initiation of adenogenesis (P8, avg. 1.75%) and then increased during gland morphogenesis (P14, avg. 10%). MD-epithelial cells expressed markers in common with non-MD-epithelial cells (e.g., EpCAM, FOXA2, ESR1, PGR). However, MD-epithelial cells were differentially regulated postnatally and in adults, suggesting a functional distinction in the two populations. We conclude that MET occurs not only as an epithelial damage\/repair mechanism but also during other epithelial remodeling events, which to our knowledge has not been demonstrated in other tissues.\n<\/jats:p>","DOI":"10.1007\/s00441-022-03711-z","type":"journal-article","created":{"date-parts":[[2022,11,19]],"date-time":"2022-11-19T04:35:27Z","timestamp":1668832527000},"page":"393-408","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":15,"title":["A re-appraisal of mesenchymal-epithelial transition (MET) in endometrial epithelial remodeling"],"prefix":"10.1007","volume":"391","author":[{"given":"Madelyn","family":"Spooner-Harris","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Karl","family":"Kerns","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michal","family":"Zigo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter","family":"Sutovsky","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ahmed","family":"Balboula","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8407-5437","authenticated-orcid":false,"given":"Amanda L.","family":"Patterson","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2022,11,19]]},"reference":[{"key":"3711_CR1","doi-asserted-by":"publisher","first-page":"5","DOI":"10.1186\/s40738-020-00074-3","volume":"6","author":"AF Ajayi","year":"2020","unstructured":"Ajayi AF, Akhigbe RE (2020) Staging of the estrous cycle and induction of estrus in experimental rodents: An update. 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