Local intra-uterine Ang-(1–7) infusion attenuates PGE 2 and 6-keto PGF 1α in decidualized uterus of pseudopregnant rats

摘要

Background Cyclooxygenase (COX)-derived prostanoids (PGE_2, PGI₂) are important contributors to the process of decidualization. Previous studies showed the presence of Ang-(1-7) in the primary and secondary decidualized zones of the implantation site at early pregnancy. Decreased concentrations of Ang-(1-7) were found in the decidualized uterus compared to the non-decidualized uterus of pseudopregnant rats, suggesting that low levels of Ang-(1-7) are required for successful decidualization at early pregnancy. Methods To understand the role of Ang-(1-7) in prostaglandin production in a decidualized uterus, induced by a bolus injection of sesame oil, Ang-(1-7) (24?μg/kg/h) or vehicle was then infused directly into the decidualized uterine horn using an osmotic minipump. The right horns were not injected or infused and served as non-decidualized uterine horns in both groups of animals. Results Decidualization increased PGE₂ concentration in the uterus (0.53?±?0.05 vs. 12.0?±?3.2 pmol/mg protein, p 2 (12.0?±?3.2 vs. 5.1?±?1.3 pmol/mg protein, p 2 (6-keto PGF_1α) was increased with decidualization (0.79?±?0.17 vs. 3.5?±?0.82 pmol/mg protein, p 1α in the decidualized horn (3.5?±?0.82 vs 1.8?±?0.37 pmol/mg protein, p 1a and TXB₂ were decreased by Ang-(1-7) infusion, while no difference was observed in circulating PGE₂. Although the global assessment of cleaved caspase 3 immunostaining, a marker of apoptosis, was unchanged within the Ang-(1-7) decidualized horn, there were localized decreases in cleaved caspase 3 staining in the luminal region in the decidualized uterus of Ang-(1-7)-treated rats. Conclusions These studies show that increased local uterine Ang-(1-7) alters the uterine prostaglandin environment, possibly leading to disruptions of early events of decidualization.