Regulation of progesterone receptor A and B expression in human preterm, term, and postterm placental villi

Abstract

The progesterone receptor (PR)-A/B ratio in the myometrium is reported to be closely related to labor onset. This might represent a potential target for therapeutic interventions for postterm and preterm deliveries, though the mechanisms currently remain unknown. The aim of this study was to investigate the regulation mechanism of PR-A and B expression in human preterm, term, and postterm placental villi. Experimental study. People's Hospital of Jiangsu Province, China. Singleton women of preterm (PRNIL, not in labor, n = 10), term (TNIL, not in labor, n = 10; TIL, in labor, n = 10), and postterm (PONIL, not in labor, n = 10) cesarean deliveries. The PR-A/PR-B mRNA and protein ratios were analyzed using real-time reverse transcription-polymerase chain reaction and western blots in villi from preterm, term, postterm groups. PONIL and PRNIL villi were incubated with prostaglandin F(2alpha) (PG) and indomethacin for 72 hours, respectively, and the PR-A/PR-B mRNA and protein ratios and p38 signaling pathway were explored. The PR-A/PR-B ratio was highest in TIL, followed by PRNIL, PONIL and TNIL. Indomethacin significantly up-regulated PR-B expression, thereby decreasing the PR-A/PR-B ratio (p < 0.05). Meanwhile, PG reduced the expression of PR-B and increased PR-A, leading to a significant increase in the PR-A/PR-B ratio (p < 0.05). We also determined that the PR-A/PR-B ratio was mediated through the activation of p38 mitogen-activated protein kinase. These results demonstrate that the PR-A/PR-B ratio plays a key role in the mechanisms regulating preterm, term, and postterm deliveries.