title: Mesenchymal-to-epithelial transition contributes to endometrial regeneration following natural and artificial decidualization.
abstract: Despite being a histologically dynamic organ, mechanisms coordinating uterine regeneration during the menstrual/estrous cycle and following parturition are poorly understood. In the current study, we hypothesized that endometrial epithelial tissue regeneration is accomplished, in part, by mesenchymal-to-epithelial transition (MET). To test this hypothesis, fate mapping studies were completed using a double transgenic (Tg) reporter strain, Amhr2-Cre; Rosa26-Stop(fl/fl-EYFP) (i.e., flox-stop EYFP reporter). EYFP expression was observed in Müllerian duct mesenchyme-derived stroma and myometrium, but not epithelia in young and peripubertal double Tg female mice. However, mosaic EYFP expression was observed in epithelia of double Tg mice after parturition. To ensure the observed epithelial EYFP expression was not due to leaky Amhr2 promoter activity, resulting in aberrant Cre expression, transgenic mice expressing LacZ under the control of the Amhr2 promoter (Amhr2-LacZ) were used to monitor β-galactosidase (β-Gal) activity within the uterus. β-Gal activity was not detected in luminal or glandular epithelia regardless of age, reproductive status, or degree of damage incurred within the uterus. Lastly, a unique population of transitional cells was identified that expressed the epithelial cell marker, pan-cytokeratin, and the stromal cell marker, vimentin. These cells localized predominantly to the regeneration zone in the mesometrial region of the endometrium. These findings suggest a previously unappreciated role for MET in endometrial regeneration and have important implications for proliferative diseases of the endometrium such as endometriosis.
authors.affiliation: Department of Animal Science, Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
authors.forename: Amanda L
authors.initials: AL
authors.lastname: Patterson
authors.forename: Ling
authors.initials: L
authors.lastname: Zhang
authors.forename: Nelson A
authors.initials: NA
authors.lastname: Arango
authors.forename: Jose
authors.initials: J
authors.lastname: Teixeira
authors.forename: James K
authors.initials: JK
authors.lastname: Pru
mesh_terms: D000818:Animals; D001426:Bacterial Proteins / Q000096:biosynthesis / Q000235:genetics; D054338:Cell Transdifferentiation; D003656:Decidua / Q000166:cytology / Q000187:drug effects / Q000502:physiology*; D004717:Endometrium / Q000166:cytology / Q000187:drug effects / Q000502:physiology; D030762:Estrous Cycle; D005260:Female; D015870:Gene Expression; D017930:Genes, Reporter; D006801:Humans; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008297:Male; D051379:Mice; D008822:Mice, Transgenic; D008856:Microscopy, Fluorescence; D011401:Promoter Regions, Genetic; D018000:Receptors, Peptide / Q000235:genetics; D018125:Receptors, Transforming Growth Factor beta / Q000235:genetics; D012038:Regeneration; D012715:Sesame Oil / Q000494:pharmacology
chemical_list: D001426:Bacterial Proteins; D008164:Luminescent Proteins; D018000:Receptors, Peptide; D018125:Receptors, Transforming Growth Factor beta; C084621:anti-Mullerian hormone receptor; C054562:yellow fluorescent protein, Bacteria; D012715:Sesame Oil