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.

Oocyte environment: follicular fluid and cumulus cells are critical for oocyte health

“…Within the oocyte, pyruvate is converted in mitochondria to acetyl CoA, which enters the tricarboxylic acid (TCA) cycle and electron transport chain to produce adenosine triphosphate (ATP) (61). The oocyte in turn ensures its own delivery of pyruvate by up-regulating glycolytic genes in cumulus cells (7,64).…”

“…With increased glucose, oxygen, and pyruvate consumption during oocyte maturation, the oocyte also interacts with cumulus cells to regulate delivery of amino acids and cholesterol for other cellular processes (7,46,(85)(86)(87)(88). Human oocytes with high amino acid turnover in vitro (i.e., valine and isoleucine) have lower developmental potential than those with low amino acid turnover (89).…”

“…Continued embryo implantation failure, however, implies that other factors also affect oocyte quality, perhaps through complex intrafollicular processes that control the nuclear and/or cytoplasmic maturation of the oocyte. Since less than 7% of oocytes retrieved by IVF develop into a normal embryo that yields a live birth (6), a search for improved predictors of oocyte quality has focused on ovarian cellular signalling and metabolism, particularly since metabolic disease and maternal aging adversely affect cumulus-oocyte complex (COC) interactions (7,8). This paper discusses what processes normally occur during oocyte development, how they are perturbed by various clinical conditions, and why understanding these homeostatic mechanisms may improve pregnancy outcome by IVF and diminish the multiple-birth rate by transferring fewer embryos into the uterus.…”

Exogenous Leptin Administered Intramuscularly Induces Sex Hormone Disorder and Ca Loss via Downregulation of <i>Gnrh</i> and PI3K Expression

“…Although the mechanisms mediating the influence of metabolism and nutrition on fertility are cur-rently unclear, a strong association between metabolic disorders and infertility is undeniable [23]. Seli e and Wathes DC reported that obesity and overweight, which are characterized by lipid and glucose metabolic disorders, are significantly involved in the incidence of polycystic ovary syndrome and impaired natural fertility [29,35].…”

Energy status and ovarian follicular development

“…Obesity and/or overweight as well as underweight are negatively associated with female fertility [111,112]. A decreased success in spontaneous conception, an increased rate of anovulation, and increased risks of miscarriage have been reported in obese women at reproductive age [113]. Furthermore, there are indications that maternal obesity may affect the reproductive capacity in their children [114].…”