Endocrine-Disrupting Chemicals, Gut Microbiota, and Human (In)Fertility—It Is Time to Consider the Triad

Abstract

The gut microbiota (GM) is a complex and dynamic population of microorganisms living in the human gastrointestinal tract that play an important role in human health and diseases. Recent evidence suggests a strong direct or indirect correlation between GM and both male and female fertility: on the one hand, GM is involved in the regulation of sex hormone levels and in the preservation of the blood–testis barrier integrity; on the other hand, a dysbiotic GM is linked to the onset of pro-inflammatory conditions such as endometriosis or PCOS, which are often associated with infertility. Exposure to endocrine-disrupting chemicals (EDCs) is one of the main causes of GM dysbiosis, with important consequences to the host health and potential transgenerational effects. This perspective article aims to show that the negative effects of EDCs on reproduction are in part due to a dysbiotic GM. We will highlight (i) the link between GM and male and female fertility; (ii) the mechanisms of interaction between EDCs and GM; and (iii) the importance of the maternal–fetal GM axis for offspring growth and development.

Gut microbiota-gonadal axis: the impact of gut microbiota on reproductive functions

“…Gut microbiota influences reproductive function, especially female reproductive functions, through various mechanisms, including hormone regulation, immune system modulation, nutrient metabolism, inflammatory pathways, and genital ecosystem pathway ( 94 ) ( Figure 2 ). The metabolism and regulation of circulating estrogen hormones are carried out by the enzyme GUSB, which is one of the many enzymes involved in host metabolism that are encoded by the gut microbiota ( 95 ). There is a dearth of data linking gut microbiota and female reproduction and many aspects of the gut microbiota’s influence on female reproduction are yet to be fully elucidated, nonetheless, understanding and optimizing the gut microbiota’s role in reproductive health hold promises for improving women’s reproductive outcomes and overall well-being.…”

“…Furthermore, the gut microbiota helps educate and shape the immune system by modulating the development and function of immune cells that are involved in reproductive processes ( 120 ). Imbalances in the gut microbiota during critical developmental periods may disrupt immune programming, potentially impacting fertility and pregnancy outcomes ( 95 ).…”

“…The microbiota is considered an additional organ involved in the biotransformation of xenobiotics and has an impact on the pharmacokinetics of environmental chemicals. Consequently, an altered symbiotic flora can potentially modify how chemical substances exert their toxic effects ( 191 ).…”

Endometriosis: Update of Pathophysiology, (Epi) Genetic and Environmental Involvement

“…In the long term, an endocrine disruptor can alter the microbial diversity of the microbiota. On the other hand, microbiota metabolizes part of chemicals, therefore modulating their toxicity [ 136 ]. Prenatal exposure to endocrine disruptors may promote endometriosis via altered maternal and fetal microbiota [ 137 ], resulting in abnormal sex hormone levels (as exposed earlier).…”

Pathophysiological Effects of Contemporary Lifestyle on Evolutionary-Conserved Survival Mechanisms that Disturb the Hallmarks of Health in Polycystic Ovary Syndrome

“…Endocrine disrupting chemicals are a global problem for human health and the environment (279). There is no doubt that anthropomorphic chemicals interfere with human physiology and have adverse health effects (280)(281)(282)(283). Human exposure mainly occurs through mucosal surfaces (oral, gastrointestinal, respiratory, genitourinary), or via dermal absorption.…”