Ovarian Expression of Adipokines in Polycystic Ovary Syndrome: A Role for Chemerin, Omentin, and Apelin in Follicular Growth Arrest and Ovulatory Dysfunction?

Alice Bongrani,Christelle Rame,Namya Mellouk,Pascal Froment,Marion Cornuau,Fabrice Guérif,Joëlle Dupont

doi:10.3390/ijms20153778

Abstract

Adipokines are a potential link between reproduction and energy metabolism and could partly explain some infertilities related to some pathophysiology, such as polycystic ovary syndrome (PCOS). However, adipokines were predominantly assessed in blood samples, while very little is known concerning their variations in follicular fluid (FF) and ovarian granulosa cells (GCs) of PCOS women. Thus, the objectives of our study were to investigate adiponectin, chemerin, resistin, visfatin, omentin, and apelin ovarian expression in PCOS women in comparison with controls and women with only a polycystic ovary morphology. In total, 78 women undergoing an in vitro fertilization procedure were divided into three groups: 23 PCOS women, 28 women presenting only ≥12 follicles per ovary (ECHO group), and 27 control women. Each group almost equally included normal weight and obese women. Follicular fluid (FF) concentration and granulosa cells (GCs) mRNA expression of adipokines and their receptors were assessed by ELISA and RT-qPCR, respectively. Omentin levels in FF and GC were higher in PCOS than in ECHO and control women, while apelin expression was increased in both PCOS and ECHO groups. FF chemerin concentration was predominant in normal-weight PCOS women compared to BMI (Body Mass Index)-matched ECHO and control women, while GC mRNA levels were higher in the obese PCOS group than in the ECHO one. Compared to PCOS, ECHO women had increased FF adiponectin concentrations and lower plasma AMH levels. The FF concentration of all adipokines was higher in obese subjects except for adiponectin, predominant in normal-weight women. In conclusion, women with PCOS expressed higher GC chemerin and omentin, whereas the ECHO group presented higher levels of FF adiponectin and apelin and lower plasma AMH and LH concentrations. Chemerin, omentin, and apelin expression was differently regulated in women with PCOS, suggesting their possible role in follicular growth arrest and ovulatory dysfunction characterizing PCOS pathogenesis.

Highlights

Polycystic ovary syndrome (PCOS) is a very common endocrinopathy affecting 6% to 13% of women of reproductive age and is one of the leading causes of female poor fertility [1]
Apelin enhances progesterone and estradiol secretion in human and porcine granulosa cells (GCs) cultures [19,60], it improves rat, bovine, and porcine GC proliferation, and it seems to be involved in the regulation of the bovine corpus luteum luteolysis process [61] and oocyte maturation [62]. We demonstrated that both apelin concentration in follicular fluid (FF) and apelin/APJ mRNA expression in GCs positively correlated with antral follicle count and were significantly higher in PCOS and ECHO groups, both characterized by the accumulation of small antral follicles resulting from the failed selection of a dominant follicle
We found that FF concentration and GC mRNA expression of omentin, chemerin, and APJ were significantly lower in ECHO compared to PCOS women, suggesting that these molecules could play a physiopathological role in other main features of PCOS, such as anovulatory infertility

Summary

Introduction

Polycystic ovary syndrome (PCOS) is a very common endocrinopathy affecting 6% to 13% of women of reproductive age and is one of the leading causes of female poor fertility [1]. It was initially described as the association of anovulation and clinical and/or biological hyperandrogenism (1990 National Institutes of Health-Sponsored conference). Despite its typical association with insulin resistance (IR), abdominal obesity [4], and an increased risk of developing type 2 diabetes [5], the causal relationship between reproductive and metabolic features in PCOS has not yet been fully elucidated. In PCOS, it has been suggested that an original adipose tissue dysfunction, possibly due to in utero androgen hyperexposition and leading to excessive visceral fat depots, may play a key role in determining both IR and altered androgen metabolism [8]

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