Oxytocin stimulated release of PGF₂α and its inhibition by a cyclooxygenase inhibitor and an oxytocin receptor antagonist from equine endometrial cultures

Uterine inflammation results in a poor uterine environment and early embryonic loss in the mare due to an inhibition of maternal recognition of pregnancy caused from increased prostaglandin F₂α (PGF₂α). Oxytocin binds to endometrial cell receptors to activate prostaglandin synthesis. An oxytocin receptor antagonist (Atosiban) and a cyclooxygenase inhibitor (indomethacin) both decrease PGF₂α production. The aim of this study was to evaluate the in vitro effects of Atosiban and indomethacin on equine uterine prostaglandin secretion. Equine endometrial explants were harvested on day two of behavioral estrus. Endometrial explant cultures were challenged with oxytocin (250nM) and PGF₂α concentrations were measured over time. Explants were also cultured with Atosiban and indomethacin for 6h to determine the influence on PGF₂α secretion. When endometrial explants were challenged with oxytocin, PGF₂α concentrations were greater (P<0.0001) at each time point over the 24h of culture as compared to controls. Oxytocin failed (P<0.001) to elicit PGF₂α release in explants cultured with either Atosiban or indomethacin. These findings show equine endometrial explants can be stimulated with oxytocin to increase secretion of PGF₂α and this secretion can be inhibited through an oxytocin receptor antagonist and a Cox inhibitor, suggesting that this response to oxytocin involves an oxytocin receptor mediated event that activates the prostaglandin synthesis cascade through cyclooxygenase. Furthermore, this data suggests a role for the use of these inhibitors in vivo to decrease uterine PGF₂α secretion and prevent early luteal regression and embryonic loss.