New Aspects of Corpus Luteum Regulation in Physiological and Pathological Conditions: Involvement of Adipokines and Neuropeptides

Abstract

The corpus luteum is a small gland of great importance because its proper functioning determines not only the appropriate course of the estrous/menstrual cycle and embryo implantation, but also the subsequent maintenance of pregnancy. Among the well-known regulators of luteal tissue functions, increasing attention is focused on the role of neuropeptides and adipose tissue hormones-adipokines. Growing evidence points to the expression of these factors in the corpus luteum of women and different animal species, and their involvement in corpus luteum formation, endocrine function, angiogenesis, cells proliferation, apoptosis, and finally, regression. In the present review, we summarize the current knowledge about the expression and role of adipokines, such as adiponectin, leptin, apelin, vaspin, visfatin, chemerin, and neuropeptides like ghrelin, orexins, kisspeptin, and phoenixin in the physiological regulation of the corpus luteum function, as well as their potential involvement in pathologies affecting the luteal cells that disrupt the estrous cycle.

Keywords: adipokines; corpus luteum; luteinization; luteolysis; neuropeptides; progesterone.

Figure 1

Corpus luteum development, morphological and hormonal changes during the luteal phase. VEGF—vascular endothelial growth factor, FGF—fibroblast growth factor, ANG-1—angiopoietin 1, PCNA—proliferating cell nuclear antigen, p27Kip1—cyclin-dependent kinase inhibitor 1B, P₄—progesterone, STAR—steroidogenic acute regulatory protein, CYP11A1—cytochrome P450 family 11 subfamily A member 1, HSD3B1—hydroxy-delta-5-steroid dehydrogenase, BCL-2—B-cell lymphoma-2 protein, PGE₂—prostaglandin E2, PGF_2α—prostaglandin F2α.

Figure 2

The influence of adipokines and neuropeptides on the functions of the corpus luteum in humans and various animal species. P₄—progesterone, E₂—estradiol, PGE₂—prostaglandin E₂, PGF_2α—prostaglandin 2α, PTGER—prostaglandin E receptor, PTGFR—prostaglandin F re-ceptor, PCNA—proliferating cell nuclear antigen, VEGF—vascular endothelial growth factor, FGF2—fibroblast growth factor 2, ANG-1—angiopoietin 1, BCL-2—B-cell lymphoma-2 protein, BAX—Bcl-2-associated X protein, ↑—increase, ↓—decrease.

Figure 3

Involvement of adipokines and neuropeptides in corpus luteum pathology. P₄—progesterone, LH—luteinizing hormone, ↓—decrease, ?—unknown effect.