Alterations in the Epigenetic Landscape Underlying Later-Life Health Effects Due to In-utero Exposure to Endocrine Disrupting Chemicals: A Review of Outcomes from Mice to Men

Abstract

Widespread persistence of Endocrine Disrupting Chemicals (EDCs) in the environment has mandated the need to study their potential long-term effects on human health, after acute as well aschronic exposures. The particular focus is on in utero exposure to EDCs in rodent models to look at altered epigenetic programming to result in transgenerational effects in later life of the offspring. This potentially contributes to reproductive and immune dysfunctions, obesity, cancer, and altered brain development and neurobehavioral outcomes. The literature to date establishes the transgenerational effects associated with in utero exposure to EDCs in rodent models. Hence, the aim of this review is to provide a comprehensive overview of epigenetic programming and its regulation in mammals, specially focussing on epigenetic plasticity and susceptibility to exogenous endocrine-active chemicals, EDCs, during the early developmental period, and carried forward to later life using rodent models. The available reports suggest that the key mechanism behind the long-term impact of EDCs is caused by alterations in the epigenetic programming machinery, leading to dysregulated gene expression during adult life. Studies have reported the effect of prenatal exposure to EDCs in the ovarian microRNA expression and function, highlighting ovary as an organ undergoing in utero programming. It ascertains the heightened sensitivity of the organ to exogenous hormone-active compounds, particularly during early development. In addition to this, another key aspect in this review is increased susceptibility of the brain when exposed to even minute quantities of EDCs during embryonic development, resulting in profound alterations in the structural organization of the brain and neurobehavior. Detailed analyses of variables such as folic acid and phytoestrogen content in maternal diet need to be considered as crucial factors while designing experiments and therapeutic interventions. Apart from this, appropriate animal handling during the experimental procedures to eliminate stress in animal models to ensure unbiased results is recommended.