Integrated hormonal, metabolic, and epigenetic regulation of corpus luteum function: insights into steroidogenesis, angiogenesis, and regression

The corpus luteum is a transient endocrine structure essential for establishing and maintaining early pregnancy, primarily through the secretion of progesterone. Its function is regulated by a complex interplay of hormonal, metabolic, and epigenetic factors that govern steroidogenesis, angiogenesis, and luteal cell fate. Luteotrophic hormones such as luteinizing hormone, prolactin, and prostaglandin E2 promote corpus luteum maintenance by activating key signaling pathways, including cyclic adenosine monophosphate/protein kinase A and mitogen-activated protein kinase, while luteolytic factors such as prostaglandin F2α initiate regression through calcium- and protein kinase C-mediated pathways. Recent studies have highlighted the central roles of metabolic regulators AMP-activated protein kinase and Peroxisome proliferator-activated receptor gamma and the histone methyltransferase Enhancer of zeste homolog 2 in modulating corpus luteum function. These molecules integrate hormonal signals with intracellular energy and lipid status, ultimately influencing gene expression through transcriptional and epigenetic mechanisms. Epigenetic modifications, including DNA methylation, histone acetylation/methylation, and microRNAs, act as dynamic regulators of genes involved in steroid biosynthesis, angiogenesis, and programmed cell death. This review highlights the convergence of hormonal, metabolic, and epigenetic pathways in controlling corpus luteum function and regression, offering new insights into reproductive regulation and therapeutic targets for luteal insufficiency.