Progesterone regulates inflammation and receptivity of cells via the NF-κB and LIF/STAT3 pathways

Abstract

A high concentration of blood ammonia can lead to failure of early embryo implantation in dairy cows. Progesterone (P4) is an important hormone that regulates the changes of uterine receptivity and participates in pregnancy during early implantation. However, whether P4 alleviates the harmful effects of blood ammonia is unknown. Therefore, this experiment treated bovine endometrial epithelial cells (BEEC) with ammonia chloride and P4. The results showed that ammonia decreased the viability of BEEC, upregulated the ROS level and apoptosis rate, and upregulated the expressions of Bax, Bcl-2, P53, Cyt-c, caspase-3, caspase-8 and caspase-9. It also upregulated the expressions of TLR4, NF-κB, and in turn, produced a large amount of IL-6 and downregulated the expressions of EGF and VEGF. After co-treating BEEC with ammonia and P4, P4 had no alleviating effect on cell viability, ROS and apoptosis, but downregulated the expressions of TLR4, NF-κB, IL-6, and upregulated the expressions of LIF, EGF and VEGF. Inhibition of STAT3 signaling pathway, LIF expression was not affected, and VEGF expression was down-regulated. Using LIF treated BEEC, VEGF expression was upregulated, but after the addition of inhibitors, the expression of VEGF was not upregulated by LIF. Therefore, progesterone could not alleviate the oxidative stress and apoptosis induced by ammonia in BEEC. However, progesterone ameliorated the inflammation and receptivity genes of BEEC induced by ammonia via the NF-κB and LIF/STAT3 signaling pathways.