Adiponectin and the Control of Female Reproductive Functions

Adiponectin is the most abundant protein secreted by the white adipose tissue. It circulates at high levels in the bloodstream and its serum concentration is inversely correlated with body fat mass. The wide distribution of adiponectin receptors (AdipoR1, AdipoR2, and T-cadherin) in peripheral tissues and organs allows adiponectin to exert pleiotropic effects on whole-body metabolism. Besides its well-known antidiabetic, antiatherogenic, and anti-inflammatory properties, accumulating evidence suggests a direct role for adiponectin in reproductive tissues. The mammalian ovary and the ovarian follicle express AdipoR1 and AdipoR2, and treating pig granulosa cells with adiponectin induces changes characteristic of the periovulatory period. Moreover, additive effects are observed between adiponectin and insulin in induction of granulosa cell gene expression, thus suggesting that adiponectin actions on the ovary may be mediated through its insulin-sensitizing effects. Adiponectin receptors are also detected in the uterus. In women, higher AdipoR1 and AdipoR2 gene expression was observed during the mid-secretory phase of the menstrual cycle, suggesting that adiponectin is implicated in the endometrial changes in preparation for embryo implantation. Adiponectin receptors are found in oocytes and early developing pig, rabbit, and mice embryos, and it has been demonstrated that adiponectin can increase the success of porcine embryo development to the blastocyst stage in vitro. Moreover, adiponectin concentration is two to three times greater in human fetal circulation and in umbilical cord blood, compared to adult plasma. This further indicates a role for adiponectin in fetal growth. It has been further suggested that adipose-derived and locally produced adiponectin may act as a key neuromodulator of reproductive functions. For example, the inhibition of LH and GnRH release from rat pituitary and hypothalamic cells following treatment with adiponectin provides evidence that adiponectin may also act on the release of gonadotropins. Adipose tissue is now recognized as an important factor in the complex equation by which the nutritional status regulates female reproductive functions. For example, underweight women have delayed puberty and higher risk of premature delivery, whereas overweight and obese women have early puberty and are prone to develop polycystic ovary syndrome (PCOS), gestational diabetes mellitus (GDM), and preeclampsia. Because hypoadiponectinemia is often associated with the abovementioned disorders, it has been suggested that this adipokine might play a role in the development of these pregnancy-related complications. Moreover, as these reproductive disorders often come with metabolic complications such as insulin and glucose resistance, the insulin-sensitizing effects of adiponectin may explain the observed association of this adipokine with PCOS, GDM, and preeclampsia. This review summarizes current knowledge on the role of adiponectin in female reproductive tissues and highlights mechanisms where information is available. We also discuss about the known and potential roles of adiponectin in the development of reproductive disorders.