Label-Retaining Stromal Cells in Mouse Endometrium Awaken for Expansion and Repair After Parturition

Abstract

Human and mouse endometrium undergo dramatic cellular reorganization during pregnancy and postpartum. Somatic stem cells maintain homeostasis of the tissue by providing a cell reservoir for regeneration. We hypothesized that endometrial cells with quiescent properties (stem/progenitor cells) were involved in the regeneration of the endometrial tissue. Given that stem cells divide infrequently, they can retain the DNA synthesis label [bromodeoxyuridine (BrdU)] after a prolonged chase period. In this study, prepubertal mice were pulsed with BrdU and after a 6-week chase a small population of label-retaining stromal cells (LRSC) was located primarily beneath the luminal epithelium, adjacent to blood vessels, and near the endometrialmyometrial junction. Marker analyses suggested that they were of mesenchymal origin expressing CD44 + , CD90+ , CD140b + , CD146 + , and Sca-1 + . During pregnancy, nonproliferating LRSC predominately resided at the interimplantation/placental loci of the gestational endometrium. Immediately after parturition, a significant portion of the LRSC underwent proliferation (BrdU + /Ki-67 + ) and expressed total and active b-catenin. The b-catenin expression in the LRSC was transiently elevated at postpartum day (PPD) 1. The proliferation of LRSC resulted in a significant decline in the proportion of LRSC in the postpartum uterus. The LRSC returned to dormancy at PPD7, and the percentage of LRSC remained stable thereafter until 11 weeks. This study demonstrated that LRSC can respond efficiently to physiological stimuli upon initiation of uterine involution and return to its quiescent state after postpartum repair.

Mapping of estradiol binding sites through receptor micro-autoradiography in the endometrial stroma of early pregnant mice

“…These results reinforce previous studies from our group showing that the mouse endometrium presents a compartmentalization similar to that of the human endometrium (Oliveira et al 1995(Oliveira et al , 1998Zorn et al 1995;Greca et al 1998;Salgado et al 2009aSalgado et al , b, 2011Salgado et al , 2013Favaro et al 2014). While the superficial stroma (functional layer in humans) commits with decidualization, the deep stroma (basal layer) remains undifferentiated and contributes to reconstruct the endometrium after pregnancy (Abrahamsohn 1983; Kleinfeld and O'Shea 1983;Favaro et al 2014;Cao et al 2015).…”

Loss of Endometrial Plasticity in Recurrent Pregnancy Loss

“…As is the case for most adult tissues, resident and bone marrow‐derived MSCs are critical for endometrial homeostasis and tissue repair . Menstruation, miscarriage, and parturition impose a constant need for recruitment and activation of endometrial progenitor cells.…”

Regeneration capacity of the endometrium: endometrial stem cells

“…[15] Taze elde edilen endometrial hüc-relerin yaklaık %5'ini SP hücrelerinin oluturdu¤u gösterilmitir. [17] Bu hücrelerin endometriumda kan damarları çevresinde, hem bazal hem de fonksiyonel tabakalar içerisinde yerletikleri gösterilmitir. [17] Yapılan flow sitometrik çalımalarda SP hücreleri-nin CD31+ endotelial hücrelerden (%51), CD326+ (EpCAM) epitelial hücrelerden (%27) ve CD10+ veya PDGFR-b+ stromal hücre (%10-14) grupların-dan olutukları gösterilmitir.…”

“…[17] Bu hücrelerin endometriumda kan damarları çevresinde, hem bazal hem de fonksiyonel tabakalar içerisinde yerletikleri gösterilmitir. [17] Yapılan flow sitometrik çalımalarda SP hücreleri-nin CD31+ endotelial hücrelerden (%51), CD326+ (EpCAM) epitelial hücrelerden (%27) ve CD10+ veya PDGFR-b+ stromal hücre (%10-14) grupların-dan olutukları gösterilmitir. [16] Benzer yerleimde bulunan ve main popülasyon (MP) hücreleri olarak adlandırılan hücreler ise Hoechst boyasını hücre dıına çıkarma yetilerinin olmaması ile SP hüc-relerinde ayrılırlar.…”