The role of adiponectin in reproduction: from polycystic ovary syndrome to assisted reproduction

Abstract

Objective: To summarize the effects of the adipokine adiponectin on the reproductive endocrine system, from the hypothalamic-pituitary axis to the gonads and target tissues of the reproductive system.

Design: A Medline computer search was performed to identify relevant articles.

Setting: Research institution.

Intervention(s): None.

Result(s): Adiponectin is a hormone secreted by adipose tissue that acts to reduce insulin resistance and atherogenic damage, but it also exerts actions in other tissues. Adiponectin mediates its actions in the periphery mainly via two receptors, AdipoR1 and AdipoR2. Adiponectin receptors are present in many reproductive tissues, including the central nervous system, ovaries, oviduct, endometrium, and testes. Adiponectin influences gonadotropin release, normal pregnancy, and assisted reproduction outcomes.

Conclusion(s): Adiponectin, a beneficial adipokine, represents a major link between obesity and reproduction. Higher levels of adiponectin are associated with improved menstrual function and better outcomes in assisted reproductive cycles.

FIGURE 1

Adipose tissue functions as an endocrine gland. Adipose tissue secretes proteins and lipids and metabolizes hormones that regulate not only energy homeostasis, but also influence reproduction, immune function, and cardiovascular disease and hypertension. CETP = cholesteryl ester transfer protein; FFA = free fatty acids; IL = interleukin; LPL = lipoprotein lipase; TNF = tumor necrosis factor.

FIGURE 2

Adiponectin acts through the indicated pathways to influence organs involved in male and female reproduction. ACC = acetyl CoA carboxylase; AMPK = adenosine monophosphate–activated protein kinase; IGF = insulin-like growth factor; IL = interleukin; MAPK = mitogen-activated protein kinase; PPAR = peroxisome proliferator–activated receptor. SLC2A1 (GLUT1) = soluble carrier family 2 (facilitated glucose transporter) member 1; SLC2A3 (GLUT3) = soluble carrier family 2 (facilitated glucose transporter) member 3.

FIGURE 3

Molecular structure of adiponectin and its receptors AdipoR1 and AdipoR2 and the indicated signaling pathways in muscle, adipose tissue, and liver. Adiponectin occurs in three molecular forms with globular and coiled domains: trimeric (low molecular weight), hexameric (middle molecular weight), or multimeric (high molecular weight. Two trimers associate to form a disulfide-linked hexamer (MMW). The HMW complex consists of 12–18 monomers and is most active in suppressing hepatic glucose production. The trimeric form is most potent for induction of AMPK activation and fatty acid β-oxidation in skeletal muscles. G6-pase = glucose-6-phosphatase; Glut = glucose transporter; IRS = insulin receptor substrate; mTOR= mammalian target of rapamycin; other abbreviations as in Figure 2.