Ovulation, Implantation and Placentation in Females with Obesity and Metabolic Disorders: Life in the Balance

Antonio      Gonzalez-Bulnes; Pilar      Pallares; Cristina      Ovilo

doi:10.2174/187153011797881193

Abstract

Obesity due to endocrine and metabolic disorders causing dysfunctions of appetite-regulating pathways and energy balance is an increasingly concerning issue. Such form of obesity is mainly caused by the failure of elevated levels of the hormone leptin (LEP) to suppress feeding and mediate weight loss; the syndrome, caused by disruptions of signal transduction processes at the level of leptin receptors (LEPR), has been named as leptin resistance. Alterations in genes coding for LEPR and other hypothalamic factors in obese individuals have been related to low rates of pregnancies and deliveries. Fertility depends mainly on the success of processes involving ovulation, fertilization, implantation, placentation and embryo development; processes that seem to be affected in obese females. However, mechanistical research in human beings is very difficult to undertake, especially in reproductive issues, for both technical and ethical reasons. Thus, investigation is usually taken on animal models. Most of the studies have been carried out in mice, in which mutations in LEP and LEPR genes cause severe obese phenotypes (Leprob/ob and Leprdb/db mouse); in addition, such genotypes are infertile. However, total loss of LEPR function by monogenic disorders in humans, unlike mice, are really scarce. Functional alterations by LEPR gene polymorphisms are more common; the same has been found in the swine, an animal model very close to human. This review outlines, from results of translational animal research and clinical studies, the factors, mechanisms and pathways involved in the reproductive failures of individuals with metabolic disorders during the critical period from ovulation to completion of placentation and early-embryo development.

Keywords: Female-reproduction, infertility, leptin, leptin-receptor, metabolism, nutrition, obesity, endocrine, metabolic disorders, adipocytes, transcriptional activators, co-activators