Discovery of a possible role of asprosin in ovarian follicular function

Abstract

Asprosin is a novel fasting-induced protein encoded by fibrillin-1 (FBN1) gene, produced when FBN1 is cleaved by the enzyme furin, and is associated with insulin resistance and polycystic ovarian syndrome in humans. To characterize mRNA abundance of FBN1, furin, and the presumed asprosin receptor, olfactory receptor family 4 subfamily M member 1 (OR4M1) in granulosa (GC) and theca cells (TC), and identify hormones regulating FBN1 mRNA expression, GC and TC from small (1-5 mm; SM) and large (>8 mm; LG) follicles were collected from ovaries of heifers obtained at an abattoir and used for real-time PCR gene expression analysis or in vitro evaluation of hormone regulation and asprosin effects. SMTC had 151-fold greater (P < 0.05) FBN1 mRNA abundance than SMGC, and LGTC had 50-fold greater FBN1 mRNA than LGGC. In contrast, OR4M1 mRNA was 81-fold greater in SMGC than LGGC and did not differ from SMTC, but LGTC had 9-fold greater OR4M1 mRNA than LGGC. Furin mRNA was 2.6-fold greater in SMTC than SMGC, but did not differ among follicular sizes. In cultured TC, leptin, insulin, LH, IGF1 and steroids did not affect FBN1 mRNA, but TGFβ1 increased (P < 0.05) FBN1 mRNA by 2.2-fold; EGF and FGFs increased FBN1 mRNA by 1.3- to 1.5-fold. Asprosin enhanced LH-induced TC androstenedione production, reduced IGF1-induced TC proliferation, and had no effect on progesterone production. Developmental regulation of FBN1, furin and OR4M1 along with direct effects of asprosin on TC suggests that asprosin may be a novel regulator of ovarian follicular function.

Asprosin—A Fasting-Induced, Glucogenic, and Orexigenic Adipokine as a New Promising Player. Will It Be a New Factor in the Treatment of Obesity, Diabetes, or Infertility? A Review of the Literature

“…The role of asprosin and OLFR734 in ovary function and female fertility is currently unclear. However, Maylem et al [ 44 ] suggest that asprosin may be an important factor that regulates the function of ovarian follicles. The expression of both the asprosin precursor, namely FBN1, and its putative OR4M1 receptor (olfactory receptor family 4 subfamily M member 1), significantly varies between large and small granulosa and theca cells.…”

A pancancer overview of FBN1, asprosin and its cognate receptor OR4M1 with detailed expression profiling in ovarian cancer

“…Detection of peripherally expressed olfactory receptors (ORs) is now well-documented; despite initial beliefs for localised expression of these receptors solely within the olfactory epithelium of the nasal cavity ( 12 ). Existing data suggest that expression of OLFR734 (and its orthologue OR4M1) may involve the testis, whilst emerging evidence further indicates that expression may also extend to other reproductive tissues, such as the ovaries, with further implications for fertility in mammals ( 13 , 14 ). Recent data present expression of this receptor in the ovaries of murine and bovine samples, supporting an auto/paracrine circuit between asprosin and OR4M1 which may be implicated in female fertility, as well as healthy ovarian follicular function ( 14 ).…”

“…Existing data suggest that expression of OLFR734 (and its orthologue OR4M1) may involve the testis, whilst emerging evidence further indicates that expression may also extend to other reproductive tissues, such as the ovaries, with further implications for fertility in mammals ( 13 , 14 ). Recent data present expression of this receptor in the ovaries of murine and bovine samples, supporting an auto/paracrine circuit between asprosin and OR4M1 which may be implicated in female fertility, as well as healthy ovarian follicular function ( 14 ). However, expression of OR4M1 is yet to be explored in human tissues past the testis, with the exception of peripheral blood mononuclear cell expression in cases of traumatic brain injury ( 15 ).…”

The ovarian follicle of ruminants: the path from conceptus to adult

“…It is important to recognise that monogastrics typically achieve average body fat percentages that are greater than those achieved by ruminants, so the roles of the adipokines could differ significantly between these two types of animals. However, recent research with heifer tissues has shown strong expression of the precursor of asprosin (fibrillin 1 (FBN1)) in theca cells, with regulation by TGFB1, epidermal growth factor and FGFs; furthermore, asprosin inhibits IGF1-stimulated proliferation and enhances LH-induced androstenedione production (Maylem et al 2021).…”