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

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.

Keywords: PCOS; adipokines; follicular fluid; human granulosa cells; polycystic ovary morphology.

Figure 1

Clinical parameters, hormonal data, and in vitro fertilization procedure outcomes in patients of different studied groups. (A) Follicle counts assessed by transvaginal ultrasound, (B) plasma AMH concentration, (C) plasma LH concentration, (D) number of oocytes withdrawn during transvaginal retrieval, and (E) number of embryos obtained after in vitro fertilization. For A panel, see Table 1 for the data number per group. For the B, C, D, and E panels, the data were pooled in three groups (n = 27, n = 28, n = 23 for controls, ECHO, and PCOS groups, respectively) according to the pathological condition, as the BMI effect was not significant and no interaction between the BMI and pathological condition effect was found. The values are expressed as mean ± standard errors of means. °° indicates significant difference (p < 0.01) between normal-weight and obese subjects; * indicates significant difference vs. controls (* p < 0.05, ** p < 0.01, *** p < 0.001); ### indicates significant difference (p<0.001) vs. ECHO women.

Figure 2

Follicular fluid adiponectin and chemerin concentration and mRNA expression of AdipoR1(Adiponectin receptor 1), CMKLR1, and CCRL2 in granulosa cells of obese and normal-weight PCOS, ECHO, and control groups. (A) Follicular fluid (FF) adiponectin concentration assessed by ELISA and (B) AdipoR1 mRNA levels in granulosa cells (GCs) quantified by RT-PCR within the six different groups; (C, D) chemerin levels in FF and GC; (E, F) mRNA levels of CMKLR1 and CCLR2 in GC. The values are expressed as mean ± standard errors of means (n = 12 for normal-weight controls, n = 13 for normal-weight ECHO, n = 13 for normal-weight PCOS, n = 15 for obese controls, n = 15 for obese ECHO, and n = 10 for obese PCOS). ° indicates significant difference between normal-weight and obese subjects (°° p < 0.01, °°° p < 0.001); * indicates significant difference vs. controls (*** p < 0.001); # indicates significant difference vs. ECHO women (# p < 0.05, # # # p < 0.001).

Figure 3

Follicular fluid resistin, visfatin, and omentin concentration and mRNA expression of omentin in granulosa cells of obese and normal-weight PCOS, ECHO, and control groups. (A) Follicular fluid (FF) resistin, (B) visfatin, and (C) omentin concentrations assessed by ELISA; (D) mRNA omentin levels in granulosa cells (GCs) quantified by RT-PCR within the six different groups. The values are expressed as mean ± standard errors of means (n = 12 for normal-weight controls, n = 13 for normal-weight ECHO, n = 13 for normal-weight PCOS, n = 15 for obese controls, n = 15 for obese ECHO, and n = 10 for obese PCOS). °°° indicates significant difference (p < 0.001) between normal-weight and obese subjects; * indicates significant difference vs. controls (* p < 0.05, ** p < 0.01, *** p < 0.001); ### indicates significant difference (p < 0.001) vs. ECHO women.

Figure 4

Follicular fluid apelin concentration, mRNA expression of apelin and its receptor, APJ, in GCs of obese and normal-weight PCOS, ECHO, and controls groups and correlations of apelin FF levels and apelin or APJ mRNA expression in GCs. (A) Follicular fluid (FF) apelin concentration assessed by ELISA; (B) apelin and (C) APJ mRNA levels in granulosa cells (GC) quantified by RT-PCR within the six different groups; (D) correlation between FF concentration and GC expression of apelin; correlations between APJ mRNA levels in GCs; and (E) apelin FF concentration and (F) apelin mRNA levels in GCs. The values are expressed as mean ± standard errors of means (n = 12 for normal-weight controls, n = 13 for normal-weight ECHO, n = 13 for normal-weight PCOS, n = 15 for obese controls, n = 15 for obese ECHO, and n = 10 for obese PCOS). °°° indicates significant difference (p < 0.001) between normal-weight and obese subjects; *** indicates significant difference (p < 0.001) vs. controls; ### indicates significant difference (p < 0.001) vs. ECHO women.