Serum and follicular fluid chemerin and chemerin mRNA expression in women with polycystic ovary syndrome: Systematic review and meta‐analysis

Abstract

Introduction Polycystic ovary syndrome (PCOS) is one of the most common endocrine disorders among women of reproductive age. Chemerin, a novel adipokine, is involved in inflammation, energy metabolism, adipogenesis, angiogenesis and insulin secretion in the adipose cells and ovary. This systematic review with meta‐analysis aimed to compare serum and follicular fluid (FF) chemerin and ovarian chemerin mRNA expression among women with PCOS and non‐PCOS. Methods Electronic databases including Web of Science, PubMed, Google Scholar, Scopus, Cochrane and CINAHL were used for a comprehensive search through April 2021. Of the 174 articles initially identified, 22 studies met the eligibility criteria. A random‐effects model with a weighted mean difference (WMD) and 95% confidence interval (CI) was performed to compare the outcomes between groups. Subgroup and sensitivity analyses were performed to detect the sources of heterogeneity. Results Women with PCOS compared to without PCOS showed significantly higher serum chemerin [WMD: 12.02 pg/ml (95% CI: [10.92, 13.13]), p < .001], chemerin mRNA expression [WMD: 0.38% (95% CI [0.25, 0.52]), p = .001] and FF chemerin [(WMD): 41.7 pg/ml (95% CI [17.89, 65.5]) p < .001]. Further, serum chemerin remained high in PCOS women even with subgroup analysis based on body mass index (BMI) or sample size (p < .001). Serum chemerin was higher in women with PCOS and higher BMI [(WMD): 3.29 pg/ml (95% CI: [2.73, 3.384]), p < .001]. The expression of chemerin mRNA was significantly higher in the PCOS group compared to the control group [WMD: 0.38% (95% CI [0.25, 0.52]), p < .001]. Conclusion Serum and FF chemerin and mRNA expression were higher in the PCOS group compared to the controls. Further, serum chemerin was higher in PCOS women with higher BMI compared to lower BMI. The present findings illustrate that chemerin may be associated with PCOS status and BMI, independently.

The Complex Roles of Adipokines in Polycystic Ovary Syndrome and Endometriosis

“…However, the majority of classical studies addressing the role of adipokines in PCOS examined levels of circulating adipokines [ 106 ]. Further studies examined adipokine levels in follicular fluid (FF) or their gene expression in the ovaries of PCOS patients [ 107 , 108 , 109 ]. In vitro studies were performed to elucidate the molecular mechanisms underlying adipokine action in this disease [ 110 ].…”

“…A major, recent meta-analysis comparing chemerin serum levels in women with and without PCOS, including 77 case-control studies with 8239 participants, reported significantly elevated circulating chemerin levels in PCOS patients with standard mean differences (SMD) of 1.87 with a 95% CI from 1.35 to 2.40 ( p < 0.001) [ 106 ]. A further meta-analysis including 22 studies with 2256 participants also reported a significant increase in serum chemerin levels of PCOS patients in comparison to women without PCOS ( p < 0.001) [ 109 ]. A subgroup analysis revealed chemerin serum levels to be significantly higher in overweight/obese women with PCOS (BMI > 25 kg/m 2 ) than in overweight/obese women without PCOS ( p < 0.001).…”

Chemerin: A Functional Adipokine in Reproductive Health and Diseases

“…Chemerin was evidenced as a valuable biomarker for diagnosis in a wide range of diseases, including obesity [ 145 ], cardiovascular diseases [ 146 ], T2DM [ 146 ], male subfertility [ 45 ], PCOS [ 86 ], and cytomegalovirus-induced intrauterine infection [ 147 ]. However, researchers and physicians should dissect the differential patterns of chemerin isoforms varied in diverse physiopathological microenvironments by using the mass spectrometry analysis or antibodies against specific chemerin isoforms [ 148 ].…”

“…Chemerin expression was found to be significantly increased in ovarian tissues [ 86 ], granulosa-lutein cells [ 87 ], and adipose tissues [ 88 ] in women with PCOS patients relative to normal individuals. CMKLR1 expression was also up-regulated in granulosa-lutein cells from women with PCOS relative to the healthy subjects [ 87 , 89 , 90 ].…”

“…CMKLR1 expression was also up-regulated in granulosa-lutein cells from women with PCOS relative to the healthy subjects [ 87 , 89 , 90 ]. There is extensive literature reporting that chemerin levels in blood samples and follicular fluids (FF) were significantly enhanced in PCOS patients relative to healthy women [ 86 , 91 , 92 , 93 , 94 ]. Serum chemerin values were correlated with other adipokines values (leptin, r = 0.508; adiponectin, r = −0.36; leptin/adiponectin ratio, r = 0.605) [ 95 ], and positively correlated with BMI [ 95 ], the incidence of abortion [ 96 ], and assisted reproductive failure [ 97 ] in PCOS patients.…”