ESR1 Regulates Fecundity and Functions in Sheep Endometrial Stromal Cells

Area of Science:

• Reproductive Biology
• Endocrinology
• Molecular Genetics

Background:

• Endometrial stromal cell (ESC) plasticity is vital for successful embryo implantation and development.
• The genetic regulation of ESC function, particularly by estrogen signaling, remains incompletely understood.
• Estrogen Receptor 1 (ESR1) is a key mediator of estrogenic effects in reproductive tissues.

Purpose of the Study:

• To investigate the role of ESR1 in regulating ovine endometrial stromal cell function.
• To elucidate the molecular mechanisms by which ESR1 influences sheep fecundity.
• To understand the basis for high reproductive efficiency in Hu sheep related to endometrial function.

Main Methods:

• Analysis of ESR1 tissue distribution in ovine reproductive and non-reproductive organs.
• Quantification of ESR1 mRNA and ERα protein expression in the endometrium of high- and low-fecundity Hu sheep.
• In vitro studies involving ESR1 knockdown in ovine ESCs to assess effects on proliferation, apoptosis, cell cycle, and migration.

Main Results:

• ESR1 is highly expressed in ovine reproductive organs, especially the endometrium.
• ESR1 and ERα are upregulated in the endometrium of high-fecundity Hu sheep.
• ESR1 knockdown in ESCs inhibited proliferation, induced apoptosis (via Caspase3/9), caused G0/G1 cell cycle arrest (via P53/P21), and impaired migration.

Conclusions:

• ESR1 critically regulates key functions of ovine endometrial stromal cells, including proliferation, apoptosis, cell cycle progression, and migration.
• ESR1 is a significant determinant of sheep fecundity.
• These findings provide mechanistic insights into the enhanced reproductive efficiency observed in Hu sheep.