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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


Affiliations
1 P.G. & Research Department of Advanced Zoology and Biotechnology, Government College for Men, Chennai − 600035, Tamil Nadu, India
2 Endocrine Disruption and Reproductive Toxicology (EDART) Laboratory, SRM Institute of Science and Technology, Chennai − 603203, Tamil Nadu, India
     

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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.

Keywords

Adult Health, Endocrine Disrupting Chemicals (EDCs), Epigenetic Programming, Intrauterine Exposure.
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  • 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

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Authors

S. Winkins Santosh
P.G. & Research Department of Advanced Zoology and Biotechnology, Government College for Men, Chennai − 600035, Tamil Nadu, India
Christy Lite
Endocrine Disruption and Reproductive Toxicology (EDART) Laboratory, SRM Institute of Science and Technology, Chennai − 603203, Tamil Nadu, India
Glancis Luzeena Raja
Endocrine Disruption and Reproductive Toxicology (EDART) Laboratory, SRM Institute of Science and Technology, Chennai − 603203, Tamil Nadu, India
K. Divya Subhashree
Endocrine Disruption and Reproductive Toxicology (EDART) Laboratory, SRM Institute of Science and Technology, Chennai − 603203, Tamil Nadu, India
Kamalini Esther Kantayya
Endocrine Disruption and Reproductive Toxicology (EDART) Laboratory, SRM Institute of Science and Technology, Chennai − 603203, Tamil Nadu, India
S. Barathi
Endocrine Disruption and Reproductive Toxicology (EDART) Laboratory, SRM Institute of Science and Technology, Chennai − 603203, Tamil Nadu, India

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.

Keywords


Adult Health, Endocrine Disrupting Chemicals (EDCs), Epigenetic Programming, Intrauterine Exposure.

References





DOI: https://doi.org/10.18311/jer%2F2021%2F28038