Obesity and the reproductive system disorders: epigenetics as a potential bridge.

Ana B Crujeiras,Felipe F Casanueva

doi:10.1093/humupd/dmu060

Abstract

Obesity and overweight are significantly involved in several reproductive pathologies contributing to infertility in men and women. In addition, several cancers of the reproductive system, such as endometrial, ovarian, breast, testicular and prostate cancers, are strongly influenced by obesity. However, the molecular mechanisms involved in the association between obesity and reproductive disorders remain unclear. Our proposal is to review the current scientific evidence regarding the effect of obesity-related factors as the core of the collective mechanisms directly and indirectly involved in the relationship between obesity and reproductive disorders, with a special and original focus on the effect of the obesity state microenvironment on the epigenetic profile as a reversible mechanistic link between obesity and the reproductive disorders. A PubMed search was performed using keywords related to obesity and adipose-related factors and epigenetics and associated with keywords related to reproduction. Full-text articles and abstracts in the English language published prior to 31 December 2013 were reviewed. The obesity state notably contributes to a reproductive dysfunction in both men and women, ranging from infertility to oncological outcomes. Several epidemiological and experimental studies demonstrate that factors secreted by the adipose tissue and gut in an obesity state can directly induce reproductive disturbances. Relevantly, these same factors are able to alter the epigenetic regulation of genes, a dynamic and reversible mechanism by which the organism responds to environmental pressures critical to the reproductive function. This review outlines the evidence showing that the association between the reproductive pathologies and obesity is not inevitable but is potentially preventable and reversible. The epigenetic marks related to obesity could constitute a therapeutic target for the reproductive disorders associated with obesity.

Highlights

Obesity is a major health problem for all countries due to its increasing prevalence and its substantial health implications related to chronic disease and mortality
This process results in an adipose tissue dysfunction and the pathological consequences of obesity that include the development of other diseases, such as diabetes mellitus, heart disease, neurological disease and some forms of cancer (Bray, 2004)
The molecular mechanisms involved in these associations require further elucidation, the molecular etiology of reproductive disease associated with obesity could be the epigenetic changes that could be either the result of, or cause, obesity

Summary

Introduction

Obesity is a major health problem for all countries due to its increasing prevalence and its substantial health implications related to chronic disease and mortality. Excess energy is stored in fat cells that enlarge and/or increase in number This process results in an adipose tissue dysfunction and the pathological consequences of obesity that include the development of other diseases, such as diabetes mellitus, heart disease, neurological disease and some forms of cancer (Bray, 2004). In addition to the widely known relationships of obesity with cardiovascular disease and diabetes mellitus, obesity itself is thought to be a relevant risk factor for reproductive disorders. Overweight and obesity have been demonstrated to be important risk factors for several types of cancers including those that involve the reproduction-related tissues. We review the current scientific evidence regarding the effects of obesity-related factors that form the core of the collective mechanisms that are directly and indirectly involved in the relationship between obesity and reproductive disorders, with a special and original focus on the effects of obesity-state microenvironment on epigenetic profile as a reversible mechanistic link between obesity and the reproductive disorders

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