Expression of purinergic receptor P2Y, G-protein coupled 2, is regulated by estrogen during the estrous cycle in mouse uterus

Elucidating the molecular intricacies governing uterine function is crucial for reproductive success. The purinergic receptor P2Y, G-protein coupled 2 (P2ry2), regulates critical cellular processes, and we investigated the mechanisms by which estrogen regulates P2ry2 expression in the mouse uterus using in vivo models. Uterine P2ry2 expression was analyzed across the estrous cycle in female mice using gene and protein expression analyses. To confirm hormonal regulation, ovariectomized mice were treated with β-estradiol and/or an Estrogen receptor Antagonist ICI 182,780. Our findings revealed a dynamic pattern of P2ry2 expression, which increased during the proestrus and estrus stages and decreased during metestrus and diestrus. P2ry2 expression was rapidly elevated following β-estradiol administration, an effect that was diminished by the Estrogen receptor Antagonist. This indicates that estrogen activates P2ry2 expression through Estrogen receptor alpha. Additionally, P2Y2 protein was localized in the luminal epithelium and glandular epithelium. In conclusion, P2ry2 expression in the mouse uterus is tightly regulated by estrogen and is predominantly localized in the epithelial compartment, suggesting P2Y2 is closely associated with endometrial remodeling and may play a potential role in uterine tissue repair.