Adiponectin Induces Periovulatory Changes in Ovarian Follicular Cells

Abstract

Adiponectin, the most abundantly synthesized protein in adipose tissue, has plieotropic effects on liver, muscle, endothelium, placenta, and other tissues. We examined direct effects of recombinant porcine adiponectin on porcine ovarian granulosa cells in vitro. We demonstrate that adiponectin, at physiologically relevant levels (10-25 microg/ml), provokes expression of genes associated with periovulatory remodeling of the ovarian follicle over a time frame of 6-24 h. These include cyclooxygenase-2, prostaglandin E synthase, and vascular endothelial growth factor. Adiponectin modulates steroid synthetic protein gene expression, increasing steroidogenic acute regulatory protein transcript abundance and reducing cytochrome P450aromatase. Adiponectin has antidiabetic properties and sensitizes tissues to insulin. We show that it interacts with both LH and insulin in inducing expression of cyclooxygenase-2 transcripts in granulosa cells. We determined that the MAPK pathway, via phosphorylation of ERK1/2, is involved in mediation of the adiponectin signal in ovarian granulosa cells, rather than protein kinase A or the classic adiponectin transducer, AMP-activated protein kinase. Adiponectin synthesis is reduced in obesity, and our findings suggest that this reduction plays a role in obesity-related ovarian dysfunction.

The ‘beneficial’ adipokines in reproduction and fertility

“…40 Adiponectin does not appear to regulate its own receptor in ovarian granulosa cells. 41 The isoforms of adiponectin (trimer, hexamer and high molecular weight) are present in both porcine 41 and human follicular fluid 42 at concentrations equivalent to those found in serum. Recent studies in the rat 40 and chicken 43 indicate local production of adiponectin in theca, granulosa and luteal cells of the ovary.…”

Ovarian adipocytokines are associated with early in vitro human embryo development independent of the action of ovarian insulin

“…Although adiponectin receptors have been identified in the human ovary, it is unclear whether adiponectin itself is expressed [20]. In vitro studies have shown that adiponectin and its receptors can regulate the expression of genes that are important in steroidogenesis and ovulation [5,15,20]. Because of low adiponectin expression by human granulosa cells, it remains a question the role of adiponectin on human oocyte quality and early embryo development.…”

Adiponectine et résistine

“…Dans l'ovaire (Figure 3), l'adiponectine a été identifiée dans le liquide folliculaire (femme et truie) [22,23]. Elle est exprimée dans différents compartiments : l'ovocyte (rate) [24], le corps jaune [24], les cellules de la thèque (poule et rate) [24,25], et très faiblement dans les cellules de la granulosa de poule (à tous les stades du développement folliculaire) et de rate.…”

“…Contrairement à la rate, elle est retrouvée dans les cellules de la granulosa production des stéroïdes par les cellules de la thèque en réduisant l'expression des récepteurs de la LH et des enzymes CYP11a1 (cytochrome P450, famille 11, sous-famille a, polypeptide 1) et CYP17a1 (cytochrome P450, famille 17, sous-famille a, polypeptide 1) [28]. Dans les cellules de granulosa de porc cultivées in vitro, 1'adiponectine augmente 1'expression de molécules impliquées dans 1'ovulation, telles que Cox2 (cyclooxygénase 2), PGE2 (prostaglandine E2) et EGF (epidermal growth factor) [22]. Lors de protocoles de fécondation in vitro chez la femme, la souris et le porc, 1'adiponectine améliore la maturation ovocytaire et le développement de l'embryon [29,30].…”