Effects of asprosin on estradiol and progesterone secretion and proliferation of bovine granulosa cells

Adipokines are hormones capable of regulating various physiological process in endocrine, paracrine, and autocrine ways (Trayhurn and Wood, 2004). Ovaries are key players of mammalian female fertility and health, regulating reproductive functions and energy homeostasis through sex steroid actions (Newell-Fugate, 2017; Rettberg et al., 2014). Ovaries and adipose tissue have a close relationship via adipokine actions (Dupont et al., 2012; Nikanfar et al., 2021; Reverchon et al., 2014). Several adipokines have been reported to regulate ovarian steroidogenesis, including leptin (Dbrannian et al., 1999; Spicer and Francisco, 1997), adiponectin (Chabrolle et al., 2009; Lagaly et al., 2008), resistin (Maillard et al., 2011; Spicer et al., 2011), chemerin (Reverchon et al., 2012; Wang et al., 2012), visfatin (Reverchon et al., 2013, 2016), irisin (Poretsky et al., 2017; Ulker et al., 2020), and apelin (Rak et al., 2017; Roche et al., 2016).

Asprosin is a novel adipokine synthesized by white adipose tissue (WAT) that regulates glucose homeostasis and appetite (Duerrschmid et al., 2017; Romere et al., 2016). Asprosin is the result of a C-terminal cleavage of the profibrillin (FBN1) proprotein catalyzed by the protease furin, which also generates the mature fibrillin-1 (Romere et al., 2016). In the ovarian follicle, FBN1 transcripts and protein have been detected in granulosa cells (GC) and are highly expressed in theca cells (Maylem et al., 2021; Prodoehl et al., 2009). Interestingly, both asprosin and fibrillin-1 have been associated to ovarian function: asprosin regulates bovine theca cell androgen synthesis (Maylem et al., 2021) while fibrillin-1 regulates apoptosis of porcine cumulus cells (Zhai et al., 2013). Moreover, excessive blood asprosin concentrations have been linked to polycystic ovarian syndrome (Alan et al., 2019) and fibrillin-1 has been associated to ovarian cancer metastasis (Wang et al., 2015). It has been recently reported that, among ovarian follicular somatic cells, GC have the greatest abundance of transcripts for the OR4M1 receptor (Maylem et al., 2021), which has been described as the asprosin receptor (Li et al., 2018), although what hormones regulate OR4M1 mRNA in GC is still unknown. Moreover, asprosin has been shown to stimulate growth and ovulation rates of dominant follicles in water buffalo in vivo (Maylem et al., 2022). Nevertheless, the role of asprosin on GC function remains to be fully unveiled. The objective of this study is to characterize the effects of asprosin on bovine GC functions. We hypothesize that asprosin regulates GC steroidogenesis in a mono-ovulatory species such as cattle.

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