Publication Date
12-1-2023
Journal
The FASEB Journal
DOI
10.1096/fj.202301581R
PMID
37962238
PMCID
PMC10655894
PubMedCentral® Posted Date
12-1-2024
PubMedCentral® Full Text Version
Author MSS
Published Open-Access
yes
Keywords
Animals, Female, Humans, Mice, Pregnancy, Embryo Implantation, Endometrium, Epithelial Cells, Epithelial-Mesenchymal Transition, Mice, Knockout, Nuclear Receptor Coactivator 2, Uterus, Steroid receptor coactivator-2, mouse, endometrium, implantation, epithelium, Steroid receptor coactivator-2, mouse, endometrium, implantation, epithelium, transcriptome
Abstract
Although we have shown that steroid receptor coactivator-2 (SRC-2), a member of the p160/SRC family of transcriptional coregulators, is essential for decidualization of both human and murine endometrial stromal cells, SRC-2’s role in the earlier stages of the implantation process have not been adequately addressed. Using a conditional SRC-2 knockout mouse (SRC-2 d/d) in timed natural pregnancy studies, we show that endometrial SRC-2 is required for embryo attachment and adherence to the luminal epithelium. Implantation failure is associated with the persistent expression of Mucin 1 and E-cadherin on the apical surface and basolateral adherens junctions of the SRC-2 d/d luminal epithelium respectively. These findings indicate that the SRC-2 d/d luminal epithelium fails to exhibit a plasma membrane transformation (PMT) state known to be required for the development of uterine receptivity. Transcriptomics demonstrated that the expression of genes involved in steroid hormone control of uterine receptivity were significantly disrupted in the SRC-2 d/d endometrium as well as genes that control epithelial tight junctional biology and the emergence of the epithelial mesenchymal transition state, with the latter sharing similar biological properties with PMT. Collectively, these findings uncover a new role for endometrial SRC-2 in the induction of the luminal epithelial PMT state, which is a prerequisite for the development of uterine receptivity and early pregnancy establishment.
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Diseases Commons, Medical Sciences Commons, Obstetrics and Gynecology Commons, Women's Health Commons
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