Role of intraluteal and intrauterine prostaglandin signaling in LH-induced luteolysis in pregnant rats

Abstract

Luteal dysfunctions lead to fertility disorders and pregnancy complications. Normal luteal function is regulated by many factors, including luteinizing hormone (LH). The luteotropic roles of LH have been widely investigated but its role in the process of luteolysis has received little attention. LH has been shown to have luteolytic effects during pregnancy in rats. Stocco et al. have demonstrated the role of intraluteal prostaglandins (PGs) in LH-mediated luteolysis. However, the status of PG signaling in the uterus during LH-mediated luteolysis remains unexplored. In this study, we have examined the effect of LH-mediated luteolysis on luteal and uterine PG synthesis machinery and genes associated with activated luteal PGF2 signalling and uterine activation during different stages (mid and late) of pregnancy. Further, we analysed the effect of overall PG synthesis machinery blockage on LH-mediated luteolysis during late-pregnancy. Unlike the mid-stage of pregnancy, the expression of genes involved in PG synthesis and responsivity in late-stage pregnant rats luteal and uterine tissue increase post repeated administration of LH. Since the cAMP/PKA pathway mediates LH-mediated luteolysis, we analyzed the effect of inhibition of endogenous PG synthesis on the cAMP/PKA/CREB pathway, followed by the analysis of the expression of markers of luteolysis. Inhibition of endogenous PG synthesis did not affect the cAMP/PKA/CREB pathway. However, in the absence of endogenous PGs, luteolysis could not be activated to the full extent. Our results suggest that endogenous PGs may contribute to LH-mediated luteolysis, but this dependency on endogenous PGs is pregnancy stage dependent. These findings advance our understanding of the molecular pathways that regulate luteolysis.