Abstract
Irisin is an exercise-induced myokine/adipokine in mice and humans that plays an important role in ‘browning’ of white adipose tissue and has shown great potential as a treatment for some metabolic diseases, such as obesity, insulin resistance, and inflammation. The circulating irisin level is reported to be associated with exercise, obesity, diet, diseases, and exposure to different pharmacological agents. Several studies have attempted to characterize the role of irisin in PCOS and other reproductive diseases, but contradictory results have been reported. Our previous study showed that irisin may serve further functions in folliculogenesis and fertility. In this review, we present the current knowledge on the physiology of irisin and its role in gonadal axis. Firstly, we describe irisin circulating levels and speculate on the potential mechanisms involved in irisin secretion and regulation. Then, we focus on the irisin levels in PCOS, and explore the relationships between, BMI, insulin resistance, and hyperandrogenism. Finally, we present the results from animal interventional studies and in vitro experiments to investigate the relationship between irisin and gonadal axis, indicating its novel effects on reproduction and fertility.
Highlights
Irisin is a novel cytokine that is mainly secreted from skeletal muscle and was discovered by Bostrom in 2012 [1]
Obesity has a negative impact on the outcomes of assisted reproductive technology (ART); the number of retrieved oocytes, ongoing pregnancy rate, and live birth rate are decreased in obesity [11–13]
Our study initially reported an elevated progesterone level in FNDC5knockout mice, which may be due to the downregulation of Akr1c18 gene expression, which in turn is mainly related to the removal of progesterone from the body
Summary
Irisin is a novel cytokine that is mainly secreted from skeletal muscle and was discovered by Bostrom in 2012 [1]. FNDC5, the precursor protein of irisin, can promote the development of mouse ovaries, as reported by Bastu [97] et al, showing a significant increase in the number of primary and secondary follicles Consistent with their results, our previous study showed that FNDC5-knockout mice had a decreased number of antral follicles. Some studies have reported that irisin has negative effects on ovaries and testes, significantly reducing the number of vegetative cells and Leydig cells, sperm density and mobility in male rats under irisin exposure [102], and causing a decrease in the number of primary follicles and a significant increase in ovarian fibrosis in female mice [98]. Energy metabolism directly affects the secretion of GH and IGF-I, and some studies have reported that the levels of FNDC5 and/or irisin in circulation are positively correlated with the activity of the GH/IGF-I axis [46, 119, 120]. Due to the lack of available evidence, the specific effects and mechanisms of irisin on fertility are unclear, and more in-depth research is required to develop the field
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