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

BACKGROUND: Cyclooxygenase (COX)-derived prostanoids (PGE(2,) PGI(2)) 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 PGE(2) concentration in the uterus (0.53 ± 0.05 vs. 12.0 ± 3.2 pmol/mg protein, p < 0.001, non-decidualized vs. decidualized horns); Ang-(1-7) infusion attenuated the increase of PGE(2) (12.0 ± 3.2 vs. 5.1 ± 1.3 pmol/mg protein, p < 0.01 control vs. Ang-(1-7) treated decidualized horns). The stable metabolite of PGI(2) (6-keto PGF(1α)) was increased with decidualization (0.79 ± 0.17 vs. 3.5 ± 0.82 pmol/mg protein, p < 0.001, non-decidualized vs. decidualized horns). Ang-(1-7) infusion attenuated the increase in 6-keto PGF(1α) in the decidualized horn (3.5 ± 0.82 vs 1.8 ± 0.37 pmol/mg protein, p < 0.05 control vs. Ang-(1-7) treated decidualized horns). The circulating levels of 6-keto-PGF(1a) and TXB(2) were decreased by Ang-(1-7) infusion, while no difference was observed in circulating PGE(2). 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.