Endocrine Disruptor Compounds—A Cause of Impaired Immune Tolerance Driving Inflammatory Disorders of Pregnancy?

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.

Paternal Fenitrothion Exposures in Rats Causes Sperm DNA Fragmentation in F0 and Histomorphometric Changes in Selected Organs of F1 Generation

“…Both sexes can exhibit different responses from toxicant exposures influenced by cellular and molecular processes as well as interactions between environmental chemicals and physiological molecules [60]. Furthermore, environmental toxicants present in seminal fluid have the potential to transmit the effects of paternal exposures to the offspring [61]. The current findings showed that paternal exposure to FNT did not cause any changes in the developmental landmarks among all progeny groups.…”

Membrane Hormone Receptors and Their Signaling Pathways as Targets for Endocrine Disruptors

“…There is some evidence that “classical EDCs” (phthalates, bisphenol-A, octyl- and nonyl-phenol, vinclozolin, atrazine, etc.) are especially problematic in the peri-conception phase of pregnancy when the maternal immune response is first established, and the critical events of implantation and early placentation occur [ 29 ]. In many cases, these EDs act through the nuclear estrogen receptors present in immune cells [ 30 ].…”

Evaluating the Effects of BPA and TBBPA Exposure on Pregnancy Loss and Maternal–Fetal Immune Cells in Mice

“… 47 Alterations in cellular, 48 , 49 , 50 , 51 , 52 hormonal, 53 molecular, 54 , 55 , 56 , 57 , 58 , 59 and genetic 60 mediators of immune tolerance have been linked to miscarriages. BPA 61 , 62 and TBBPA 46 exposure alters cellular and molecular components of the immune system in pregnancy. One proposed mechanism causatively linked to reduced maternal–fetal immune tolerance is disruptions in indoleamine 2,3-deoxygenase 1 (IDO1)–mediated tryptophan catabolism.…”