Abstract
Endocrine disrupting compounds (EDCs) are prevalent and ubiquitous in our environment and have substantial potential to compromise human and animal health. Amongst the chronic health conditions associated with EDC exposure, dysregulation of reproductive function in both females and males is prominent. Human epidemiological studies demonstrate links between EDC exposure and infertility, as well as gestational disorders including miscarriage, fetal growth restriction, preeclampsia, and preterm birth. Animal experiments show EDCs administered during gestation, or to either parent prior to conception, can interfere with gamete quality, embryo implantation, and placental and fetal development, with consequences for offspring viability and health. It has been presumed that EDCs operate principally through disrupting hormone-regulated events in reproduction and fetal development, but EDC effects on maternal immune receptivity to pregnancy are also implicated. EDCs can modulate both the innate and adaptive arms of the immune system, to alter inflammatory responses, and interfere with generation of regulatory T (Treg) cells that are critical for pregnancy tolerance. Effects of EDCs on immune cells are complex and likely exerted by both steroid hormone-dependent and hormone-independent pathways. Thus, to better understand how EDCs impact reproduction and pregnancy, it is imperative to consider how immune-mediated mechanisms are affected by EDCs. This review will describe evidence that several EDCs modify elements of the immune response relevant to pregnancy, and will discuss the potential for EDCs to disrupt immune tolerance required for robust placentation and optimal fetal development.
Highlights
Endocrine disrupting compounds (EDCs) are defined by their potential to alter endocrine function through mimicking or blocking the actions of endogenous hormones [1, 2]
There is mounting evidence pointing to a contribution of EDCs in adverse pregnancy outcomes, as well as infertility and subfertility
Given the critical significance of the maternal immune response in pregnancy and the substantial literature demonstrating that common EDCs interfere with key elements of the immune response relevant to pregnancy (Figure 2), it is important to consider immune dysregulation amongst the effects that EDCs may exert
Summary
Endocrine disrupting compounds (EDCs) are defined by their potential to alter endocrine function through mimicking or blocking the actions of endogenous hormones [1, 2]. They can interfere with physiological events and tissue homeostasis over the entire life cycle [2, 8,9,10] Depending on variables such as the duration, type, and dose of exposure, EDCs can exert transient or permanent impacts, to elevate long-term risk of chronic metabolic, neurological and immune diseases that may only become evident in later life [2, 9]. These outcomes stem from failure of the maternal immune response to support embryo implantation and allow robust placental development [35,36,37] These considerations raise the question of whether the adverse effects of EDCs on reproduction and pregnancy are at least partly due to mechanisms mediated by immune cells. Devising strategies to protect humans and animals from the adverse reproductive effects of EDCs will require greater understanding of the how the immune system– EDC interaction contributes
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