Minireview: Metabolism of female reproduction: regulatory mechanisms and clinical implications

Abstract

Female fertility is highly dependent on successful regulation of energy metabolism. Central processes in the hypothalamus monitor the metabolic state of the organism and, together with metabolic hormones, drive the peripheral availability of energy for cellular functions. In the ovary, the oocyte and neighboring somatic cells of the follicle work in unison to achieve successful metabolism of carbohydrates, amino acids, and lipids. Metabolic disturbances such as anorexia nervosa, obesity, and diabetes mellitus have clinically important consequences on human reproduction. In this article, we review the metabolic determinants of female reproduction and their role in infertility.

Figure 1.

The regulation of metabolism is an essential component of successful female fertility. The hypothalamus promotes feeding or satiety in response to the availability of metabolic substrate. This central control of appetite is further regulated by the peripheral regulatory hormones leptin, primarily released from adipose tissue, and ghrelin, derived from the gut, which act directly on hypothalamic neurons to suppress and promote appetite, respectively. The resulting effects of these central and peripheral interactions optimally yield a metabolic context amenable to fertility. However, both inadequate and excess metabolic substrate can impair female fertility via direct and indirect effects on ovarian function.

Figure 2.

Regulation of NPY/AgRP and POMC neuron activity via peripherally secreted hormones. Ghrelin secreted from gut during fasting increases firing of AgRP neurons and decreases action potential frequency of POMC neurons. Leptin secreted from adipose tissue increases activity of POMC neurons and diminishes activity of NPY/AgRP neurons. Estradiol increases excitatory input to POMC neurons. NPY/AgRP neurons also directly inhibit POMC perikarya.

Figure 3.

Carbohydrate, lipid, and amino acid metabolism in cumulus oocyte complexes. Glucose is taken up by cumulus cells and is converted to pyruvate via glycolysis, which then enters oocytes via gap junctions. Although glucose is also transported to the oocyte, its function is unknown and pyruvate is used as a major energy source. Cumulus cells also regulate redox status of oocytes by providing them with nicotinamide adenine dinucleotide phosphate, and transport de novo synthesized cholesterol and L-alanine taken from follicular fluid to the oocyte. Oocytes actively regulate these processes via secretion of growth factors.