The myokine Irisin: localization and effects in swine late medium and large antral ovarian follicle

Irisin is mainly synthesized by skeletal muscle tissue, where it is believed to be 9 responsible for the benefits of exercise on metabolism and cardiovascular system. 10 In adipose tissue, its best known effect is the browning of white adipocytes, 11 resulting in the increase of thermogenesis and energy expenditure. Since it has 12 been largely documented that metabolic dysfunctions can frequently be 13 associated with reductions in fertility, the possible involvement of this molecule in 14 the regulation of reproductive processes represents an issue to be addressed. On 15 this basis, the first aim of this work was the evaluation of the presence of irisin in the 16 swine ovary; then we investigated the expression of the associated molecules 17 FNDC5, PGC-1α, PPAR-γ. In order to verify a potential modulatory role both on 18 ovarian function and on the redox status, cell growth, steroidogenesis, production 19 of superoxide anion and nitric oxide, the non-enzymatic antioxidant scavengers, 20 were assessed in-vitro on granulosa cells treated with increasing concentrations of 21 irisin (50, 100 and 150 ng/ml). The data collected demonstrate the presence of irisin 22 in swine ovarian follicle. Moreover, the highest concentrations tested stimulated 23 metabolic activity and inhibited cell proliferation (p<0.05); the peptide exerted a 24 biphasic effect on progesterone (p<0.01) production and, at the highest 25 concentrations, inhibited nitric oxide while stimulated the non-enzymatic 26 antioxidant power (p<0.05). Superoxide anion and estradiol 17β were unaffected. 27 The demonstration of the local presence of irisin at the ovarian level and the 28 highlighted effects allow us to qualify this molecule as a potential physiological 29 regulator of follicular function