The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis

Abstract

Polycystic ovary syndrome (PCOS) and endometriosis are frequent diseases of the female reproductive tract causing high morbidity as they can significantly affect fertility and quality of life. Adipokines are pleiotropic signaling molecules secreted by white or brown adipose tissues with a central role in energy metabolism. More recently, their involvement in PCOS and endometriosis has been demonstrated. In this review article, we provide an update on the role of adipokines in both diseases and summarize previous findings. We also address the results of multi-omics approaches in adipokine research to examine the role of single nucleotide polymorphisms (SNPs) in genes coding for adipokines and their receptors, the secretome of adipocytes and to identify epigenetic alterations of adipokine genes that might be conferred from mother to child. Finally, we address novel data on the role of brown adipose tissue (BAT), which seems to have notable effects on PCOS. For this review, original research articles on adipokine actions in PCOS and endometriosis are considered, which are listed in the PubMed database.

Keywords: adipokine; batokine; brown adipose tissue; endometriosis; infertility; obesity; omics; polycystic ovary syndrome; single nucleotide polymorphism; white adipose tissue.

Figure 1

Proposed effects of the indicated WAT adipokines and of BAT on PCOS, based on current experimental evidence and on an assessment of the effects of the known adipokine actions on PCOS. Green arrows illustrate a beneficial effect, red arrows an adverse effect on PCOS pathophysiology. Red-green-colored arrows indicate the presence of both beneficial and adverse effects of an adipokine. BAT activation or transplantation has been reported to notably improve PCOS, although only few molecular mechanisms underlying this effect are known to date. * Novel proteomic approaches are expected to identify further batokines (XY) affecting PCOS. “↑” = increase; “↓” = decrease.

Figure 2

Proposed effect of the indicated adipokines on endometriotic tissue based on the current state of research. Additional studies are necessary to further substantiate the role of these adipokines in endometriosis. It can be expected that the recent report suggesting apelin receptor APLNR to be one of three key genes in endometriosis resulting from in silico analyses of DNA microarray data will encourage functional studies to elucidate underlying molecular mechanisms. Red arrows indicate adverse effects on endometriosis; green inhibitor arrows indicate beneficial effects. In text boxes, red arrows indicate the up-regulation and green ones the down-regulation of the respective pathways. White arrows indicate an increase or decline in the adipokine concentration in the blood/peritoneal fluid of women with endometriosis.