Prostaglandin E2 is a crucial intermediator of 17β-estradiol-induced growth factor expression in bovine endometrial cells and explants

Estradiol is a critical hormone that regulates morphological and functional changes in the bovine endometrium throughout the estrous cycle. Prostaglandin E₂ (PGE₂), a well-established inflammatory mediator, also plays an essential role in endometrial physiology. Whether PGE₂ acts as an intermediary in estradiol-related activities within the bovine endometrium remains unclear. The results revealed that 17β-estradiol at 10⁻¹⁰ M and 10⁻⁹ M induced PGE₂ secretion in endometrial explants, whereas a higher concentration (10⁻⁷ M) downregulated PGE₂ secretion. In endometrial epithelial cells, 17β-estradiol at concentrations ranging from 10⁻¹⁰ to 10⁻⁸ M stimulated PGE₂ secretion. In endometrial stromal cells, 17β-estradiol at 10⁻¹⁰ to 10⁻⁷ M concentrations promoted PGE₂ production. PGE₂ synthesis was inhibited by the mPGES-1 inhibitor MF63 [2-(6-chloro-1H-phenanthro[9,10-d]imidazol-2-yl) isophthalonitrile] in the presence of 17β-estradiol (10⁻⁹ M), highlighting mPGES-1 as a key enzyme in 17β-estradiol-induced PGE₂ production in the bovine endometrium. Furthermore, both the mRNA and protein levels of endometrial growth factors, including fibroblast growth factor 2 (FGF-2), vascular endothelial growth factor A (VEGFA), matrix metalloproteinase-2 (MMP-2), and MMP-9, were increased by 17β-estradiol (10⁻⁹ M). This effect was reversed by pretreatment with the mPGES-1 inhibitor MF63 in endometrial cells and explants. Notably, supplementation with exogenous PGE₂ restored the expression of these growth factors in the presence of both 17β-estradiol (10⁻⁹ M) and MF63. In conclusion, mPGES-1-derived PGE₂ serves as a crucial mediator of the 17β-estradiol-induced expression of FGF-2, VEGFA, MMP-2, and MMP-9 in the bovine endometrium, underscoring its significant role in regulating endometrial function.