The ovarian reserve as target of insulin/IGF and ROS in metabolic disorder-dependent ovarian dysfunctions

Abstract

It is known from long time that metabolic disorders can cause ovarian dysfunctions and affect a woman's fertility either by direct targeting follicular cells and/or the oocytes or by indirect interference with the pituitary-hypothalamic axis, resulting in dysfunctional oogenesis. Such disorders may also influence the efficiency of the embryo implantation and the quality of the embryo with permanent effects on the fertility and health of the offspring. Thanks to the expanding knowledge on the molecular mechanisms governing oogenesis and folliculogenesis in mammals, we are beginning to understand how such disorders can negatively affect this process and consequently fertility in women. In the present review, we point out and discuss how disturbance of insulin/IGF dependent signalling and increased reactive oxygen species (ROS) level in the ovary typically associated to metabolic disorders such as diabetes and obesity can dysregulate the dynamics of the ovarian reserve and/or impair the survival and competence of the oocytes.

Preventive Electroacupuncture Alleviates Oxidative Stress and Inflammation via Keap1/Nrf2/HO-1 Pathway in Rats with Cyclophosphamide-Induced Premature Ovarian Insufficiency

“…Oxidative stress has been linked to the loss in ovarian reserve produced by chemotherapy treatments, according to research [26,27]. MDA, SOD, and GSH, which are 9 BioMed Research International oxidative index-related enzymes, are routinely employed markers to assess the degree of oxidative damage.…”

Editorial: A new era: shaping women's metabolic health, fertility, and sex-related cancers

“…Although there is evidence showing that genetic aberrations can affect women reproductive capabilities ( 1 , 2 ), nutritional habits could be an important and pivotal modifiable factor impacting female fertility. Indeed, metabolic disorders have been proposed to affect woman's fertility either by directly dampen oocytes or by indirectly interfering with hormonal feedbacks ( 3 ). Moreover, an imbalanced food intake has been associated with the onset of gestational diabetes mellitus (GDM) ( 4 ).…”

Immunological and Metabolic Causes of Infertility in Polycystic Ovary Syndrome

“…In women with PCOS, metabolic disorders and increased oxidative stress lead to the abnormal functioning of the theca and granulosa cells of the ovary through the excessive insulin signaling of the IGF-1 receptors in the ovary. The ovarian reserve, oocyte survival and quality are impaired by these mechanisms [ 141 ]. In addition, IR with compensatory hyperinsulinemia induces the overproduction of androgens in the ovaries through IGF-1 receptors, leading to hyperandrogenism and its sequelae [ 142 ].…”