Department of Animal Science, Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164, USA.
Stem Cells Dev. 2013 Mar 15;22(6):964-74. doi: 10.1089/scd.2012.0435. Epub 2013 Jan 29.
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.
尽管子宫是一个组织学上活跃的器官，但协调月经/发情周期和分娩后子宫再生的机制仍知之甚少。在本研究中，我们假设子宫内膜上皮组织的再生部分是通过间质上皮转化（MET）实现的。为了验证这一假设，我们使用了一种双转基因（Tg）报告品系 Amhr2-Cre；Rosa26-Stop(fl/fl-EYFP)（即 flox-stop EYFP 报告品系）完成了命运图谱研究。在年轻和围青春期的双 Tg 雌性小鼠中，EYFP 表达仅见于苗勒管间质衍生的基质和子宫肌层，但不见于上皮细胞。然而，在分娩后的双 Tg 小鼠中，观察到上皮细胞中存在镶嵌型 EYFP 表达。为了确保观察到的上皮细胞 EYFP 表达不是由于 Amhr2 启动子活性泄漏导致异常 Cre 表达，我们使用了在 Amhr2 启动子控制下表达 LacZ 的转基因小鼠（Amhr2-LacZ）来监测子宫内的β-半乳糖苷酶（β-Gal）活性。无论年龄、生殖状态或子宫内损伤程度如何，均未检测到腔上皮或腺上皮中的β-Gal 活性。最后，鉴定出一种独特的过渡细胞群体，其表达上皮细胞标志物泛细胞角蛋白和间质细胞标志物波形蛋白。这些细胞主要定位于子宫内膜中系膜区的再生区。这些发现提示 MET 在子宫内膜再生中具有以前未被认识的作用，并且对子宫内膜的增殖性疾病（如子宫内膜异位症）具有重要意义。
