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 and the role of intraluteal prostaglandins (PGs)in LH-mediated luteolysis has been demonstrated by others. However, the status of PG signaling in the uterus during LH-mediated luteolysis remains unexplored. In this study, we utilized the repeated LH administration (4×LH)model for luteolysis induction. We have examined the effect of LH-mediated luteolysis on the expression of genes involved in luteal/uterine PG synthesis, luteal PGF2α signaling, and uterine activation during different stages (mid and late) of pregnancy. Further, we analyzed the effect of overall PG synthesis machinery blockage on LH-mediated luteolysis during late pregnancy. Unlike the midstage of pregnancy, the expression of genes involved in PG synthesis, PGF2α signaling, and uterine activation in late-stage pregnant rats' luteal and uterine tissue increase 4×LH. Since the cAMP/PKApathway mediates LH-mediated luteolysis, we analyzed the effect of inhibition of endogenous PG synthesis on the cAMP/PKA/CREBpathway, followed by the analysis of the expression of markers of luteolysis. Inhibition of endogenous PG synthesis did not affect the cAMP/PKA/CREBpathway. 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.