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Updated: Jul 11, 2025

Isolation of Mouse Endometrial Epithelial and Stromal Cells for In Vitro Decidualization
Published on: March 2, 2017
Steroid receptor coactivator-2 drives epithelial reprogramming that enables murine embryo implantation
Vineet K Maurya1, Maria M Szwarc1, David M Lonard1
1Department of Molecular and Cellular Biology, Center for Coregulator Research, Baylor College of Medicine, Houston, Texas, USA.
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-2d/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-2d/d luminal epithelium, respectively. These findings indicate that the SRC-2d/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-2d/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.
Insights
Steroid receptor coactivator-2 (SRC-2) is crucial for embryo implantation by enabling uterine receptivity. Loss of SRC-2 prevents embryo attachment, highlighting its role in early pregnancy establishment.
Area of Science:
- Reproductive Biology
- Molecular Endocrinology
- Cellular Biology
Background:
- Steroid receptor coactivator-2 (SRC-2) is known to be essential for decidualization in endometrial stromal cells.
- The role of SRC-2 in earlier stages of embryo implantation, specifically in the uterine luminal epithelium, remains inadequately addressed.
- Uterine receptivity is a critical prerequisite for successful embryo implantation and establishment of early pregnancy.
Purpose of the Study:
- To investigate the role of endometrial SRC-2 in the critical early stages of embryo implantation.
- To determine if SRC-2 is required for the plasma membrane transformation (PMT) state necessary for uterine receptivity.
- To elucidate the molecular mechanisms by which SRC-2 influences uterine receptivity and implantation.
Main Methods:
- Utilized a conditional SRC-2 knockout mouse model (SRC-2d/d) in timed natural pregnancy studies.
- Examined embryo attachment and adherence to the uterine luminal epithelium in SRC-2d/d and control mice.
- Assessed the expression of Mucin 1 and E-cadherin in the luminal epithelium.
- Performed transcriptomic analysis to identify gene expression changes in the SRC-2d/d endometrium.
Main Results:
- Endometrial SRC-2 is essential for embryo attachment and adherence to the uterine luminal epithelium.
- SRC-2d/d mice exhibit implantation failure associated with persistent apical Mucin 1 and basolateral E-cadherin expression.
- The SRC-2d/d luminal epithelium fails to undergo the plasma membrane transformation (PMT) required for uterine receptivity.
- Transcriptomics revealed disrupted expression of genes involved in steroid hormone control, epithelial tight junctions, and epithelial-mesenchymal transition (EMT) in SRC-2d/d endometrium.
Conclusions:
- Endometrial SRC-2 plays a novel and critical role in inducing the luminal epithelial PMT state.
- This SRC-2-dependent PMT is a prerequisite for establishing uterine receptivity and successful early pregnancy.
- SRC-2 regulates key molecular pathways, including those controlling epithelial integrity and plasticity, essential for implantation.
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