Systemic adiponectin treatment reverses polycystic ovary syndrome-like features in an animal model

Abstract

The present study examined the efficacy of adiponectin for regulating the reproductive, metabolic and fertility status of mice with polycystic ovary syndrome (PCOS). PCOS was induced in prepubertal (21- to 22-day-old) mice using dehydroepiandrosterone (6mg 100g-1day-1 for 25days), after which mice were administered either a low or high dose of adiponectin (5 or 15µgmL-1, s.c., respectively). PCOS mice exhibited typical features, including the presence of numerous cystic follicles, increased circulating androgens, increased body mass, altered steroidogenesis, decreased insulin receptor expression and increased serum triglycerides, serum glucose, Toll-like receptor (TLR)-4 (a marker of inflammation) and vascular endothelial growth factor (VEGF; a marker of angiogenesis). These parameters were significantly correlated with a reduction in adiponectin in PCOS mice compared with vehicle-treated control mice. Exogenous adiponectin treatment of PCOS mice restored body mass and circulating androgen, triglyceride and glucose levels. Adiponectin also restored ovarian expression of steroidogenic markers (LH receptors, steroidogenic acute regulatory protein and 3β-hydroxysteroid dehydrogenase), insulin receptor, TLR-4 and VEGF levels in control mice. Adiponectin restored ovulation in PCOS mice, as indicated by the presence of a corpus luteum and attainment of pregnancy. These findings suggest that adiponectin effectively facilitates fertility in anovulatory PCOS. We hypothesise that systemic adiponectin treatment may be a promising therapeutic strategy for the management of PCOS.

Androgens and ovarian function: translation from basic discovery research to clinical impact

“…Transplantation of BAT from control healthy rats into hyperandrogenic PCOS female rats enhances their BAT activity, increases serum adiponectin levels and ameliorates several key PCOS traits including irregular cycles and insulin resistance (Yuan et al 2016). This study also revealed that exogenous adiponectin administration recapitulated the beneficial effects from BAT transplantation (Yuan et al 2016), which was also confirmed in another hyperandrogenized mouse model of PCOS (Singh et al 2017). Moreover, the findings that transgenic mice that overexpress adiponectin are protected from the induction of androgen excess metabolic PCOS traits, while mice that lack adiponectin display exaggerated or comparable PCOS features to the classic hyperandrogenized PCOS mouse model, highlights that modulation of adipokines, such as adiponectin, may provide a promising novel therapeutic strategy for the management of PCOS (Benrick et al 2017).…”

“…At present, understanding the precise role the adipokine adiponectin plays in the development of PCOS is of particular interest. Adiponectin is important in glucose and lipid metabolism and has been observed to be decreased in women with PCOS (Manneras-Holm et al 2011) and several PCOS mouse models (Benrick et al 2017, Caldwell et al 2017, Singh et al 2017. Transplantation of BAT from control healthy rats into hyperandrogenic PCOS female rats enhances their BAT activity, increases serum adiponectin levels and ameliorates several key PCOS traits including irregular cycles and insulin resistance (Yuan et al 2016).…”

TLR2 and TLR4 Surface and Gene Expression in White Blood Cells after Fasting and Oral Glucose, Lipid and Protein Challenges: Influence of Obesity and Sex Hormones

“…However, the literature regarding TLR expression in patients with PCOS is scarce. Two studies presented data describing increased TLR4 in ovarian tissues from animal models of PCOS [54,55], and it has been reported that ovarian cumulus cells from women with PCOS presented an abnormal TLR expression [56]. Gonzalez et al [57,58] recently reported increased TLR2 expression in peripheral blood mononuclear cells in women with PCOS after ingestion of cream regardless of obesity, and a similar increase in TLR4 expression that occurred mostly in obese women with the syndrome.…”

Effects of Exogenous Adiponectin Supplementation in Early Pregnant PCOS Mice on the Metabolic Syndrome of Adult Female Offspring

“…After successful modeling, the model group (n = 39, three mice dead, three mice sacri ced) were randomly divided into two groups: maternal-PCOS group (n = 20; 0.9% sodium chloride, s.c.) and maternal-PCOS+APN group (n = 19; APN, 10 mg/kg/day, s.c.) [32]. The control group was recorded as maternal-control group (n = 10, two mice dead, three mice sacri ced; 0.9% sodium chloride, s.c.).…”