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

Abstract

Purpose We aimed to characterize the association between levels of serum and follicular fluid (FF) adipocytokines, reflected by the leptin to adiponectin ratio (L:A ratio), and oocyte quality and in vitro embryo development in women undergoing assisted reproduction. We also aimed to assess whether follicular hormonal pathways mediate this interaction. Methods We prospectively collected FF from up to four individual preovulatory follicles (n076) and fasting sera from women (n031) without endocrinopathies undergoing in vitro fertilization (IVF) at a university-based center for assisted reproduction. Leptin, total adiponectin, insulin, insulin-like growth factor 1 (IGF-1), and ovarian steriods were measured using enzyme immunoassay. Oocyte maturity, fertilization, and embryo development were assessed. Results FF leptin was similar to serum levels while FF adiponectin was lower. FF leptin (27.10±4.05 ng/mL) and the L:A ratio (11.48E−3±2.57E−3) were related to FF insulin (R 2 00.370 and 0.419, p<0.001) but not to ovarian steroids or IGF-1, whereas FF adiponectin ( 4.22±0.52 ug/mL) correlated only with leptin (R 2 0−0.138, p00.001). Oocytes from a high FF L:A ratio environment were 81 % (RR 1.81 [95%CI 0.97-3.37]) more likely to undergo successful cleavage and 117 % (RR 2.17 [95 % CI 1.06-4.44]) more likely to obtain viable cleavage morphology compared to a low FF L:A ratio environment, even when adjusted for FF insulin, an independent predictor of cleavage. Conclusions Certain adipocytokines, particularly the L:A ratio in the FF of the preovulatory follicle, are related to successful in vitro embryo development. This action may be independent of FF insulin.

Characterization of adiponectin concentrations and molecular weight forms in serum, seminal plasma, and ovarian follicular fluid from cattle

“…The FF is a product of both the transfer of blood plasma constituents across the blood follicular barrier and the secretory activity of granulosa and theca cells [41]. The local secretion of AdipoQ from ovarian cells into the FF may occur [13], and transudation of AdipoQ from the blood to FF has been previously suggested [21]. For the latter, the relative concentrations of the different MW forms in the FF versus serum may be altered because the amount of proteins in the FF depends on the MW of the protein, and the amount decreases as the MW increases [42].…”

“…In addition, a positive correlation between the AdipoQ concentrations in both matrices was observed [19]. In human follicular fluid (FF), the concentrations of AdipoQ reach approximately 20% to 25% of the corresponding serum samples and are positively correlated with the serum values [20,21].…”

Mechanisms of Adiponectin Action in Fertility: An Overview from Gametogenesis to Gestation in Humans and Animal Models in Normal and Pathological Conditions

“…Adiponectin levels are higher in FF than in plasma in women [71], and the opposite is observed in cows [30]. In human, FF adiponectin concentrations are positively correlated with the serum values [71,72,73]. In addition to the differences in adiponectin concentrations, adiponectin isoform distribution varies between the serum and FF compartments in women.…”

Association of serum and follicular fluid leptin and ghrelin levels with in vitro fertilization success

“…Others suggest that there is no correlation [28]. More recently, increased leptin levels have indicated better IVF outcomes [29]. Thus, the relationship between leptin and reproduction remains vague.…”