Abstract
The current scenario of male infertility is not yet fully elucidated; however, there is increasing evidence that it is associated with the widespread exposure to endocrine-disrupting chemicals (EDCs), and in particular to obesogens. These compounds interfere with hormones involved in the regulation of metabolism and are associated with weight gain, being also able to change the functioning of the male reproductive axis and, consequently, the testicular physiology and metabolism that are pivotal for spermatogenesis. The disruption of these tightly regulated metabolic pathways leads to adverse reproductive outcomes. The permanent exposure to obesogens has raised serious health concerns. Evidence suggests that obesogens are one of the leading causes of the marked decline of male fertility and key players in shaping the future health outcomes not only for those who are directly exposed but also for upcoming generations. In addition to the changes that lead to inefficient functioning of the male gametes, obesogens induce alterations that are “imprinted” on the genes of the male gametes, establishing a link between generations and contributing to the transmission of defects. Unveiling the molecular mechanisms by which obesogens induce toxicity that may end-up in epigenetic modifications is imperative. This review describes and discusses the suggested molecular targets and potential mechanisms for obesogenic–disrupting chemicals and the subsequent effects on male reproductive health.
Highlights
Definitive conclusions on how obesogens affect the cellular and molecular mechanisms involved in the production and function of sperm are, hard to establish
From a clinical point of view, it is imperative to identify mechanisms by which testicular metabolic pathways are compromised after exposure to obesogens
Sertoli cells (SCs) have arisen as one of the best in vitro and/or ex vivo models that have allowed researchers from this area to understand the molecular basis by which obesogens impact male fertility
Summary
Publisher’s Note: MDPI stays neutral with regard to jurisdictional claims in published maps and institutional affiliations. The endocrine system plays a central role in regulating critical biological functions as metabolism, development, reproduction, and behavior Understanding how these chemicals affect physiologic processes and initiate pathological conditions is essential to dissect the etiology of hormone-related diseases. One recent concern about the adverse effects of EDCs is the ability that some of them have to induce weight gain [6] Today these chemicals are classified as obesogens, a term coined by Blumberg and Grun in 2006 [7]. It is essential to understand how EDCs, especially obesogens, induce male infertility namely in the deregulation of the mechanisms that govern the function of the reproductive axis, sperm formation, and its functioning (Figure 1).
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