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Potential facet for prenatal arsenic exposure paradigm: linking endocrine disruption and epigenetics

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Abstract

Environmental exposure to toxicants/heavy metals during critical periods of development can influence changes in embryo and germline of the offspring; and later on affect the disease susceptibility in adults. Exposures to toxic metals or endocrine disruptors are particularly harmful during fetal development. Arsenic, a well-known toxic metalloid and reproductive toxicant is one the major concern because of its adverse and delayed health effects. Considering the complex and numerous adverse health effects of prenatal arsenic exposure, it is very difficult to identify the one single mechanism for arsenic-induced toxicity. This is further complicated due to biphasic response reported where arsenic has very different effects at low and high doses particularly during early life exposure scenario. In this review, we are focusing on prenatal arsenic exposure and its lifelong adverse effects, and their association with endocrine disruption and epigenetic changes. We provide evidence that developmental arsenic exposure alters the functional fetal epigenome in a tissue-specific manner by alterations in DNA methylation patterns, histone modifications and changes in micro RNA. Arsenic as an endocrine disruptor also affects the reproductive potential of the organism. These adverse effects of arsenic could manifest directly through classical hormone imprinting or through irreversible epigenetic modulation. Thus, understanding the association of epigenetic changes and endocrine disruption by prenatal arsenic exposure may help unravel the crucial mechanism for the development of disease later in life.

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Acknowledgements

We acknowledge Prof. Alok Dhawan, Director CSIR-IITR for overall support. This work was supported by Department of Biotechnology (DBT) Grant, Project No. GAP-302. S.G was supported by CSIR junior and senior research fellowship. A.C was supported by DBT Inspire junior research fellowship. V.S was supported by SERB Project GAP-344 fellowship.

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Gangopadhyay, S., Sharma, V., Chauhan, A. et al. Potential facet for prenatal arsenic exposure paradigm: linking endocrine disruption and epigenetics. Nucleus 62, 127–142 (2019). https://doi.org/10.1007/s13237-019-00274-3

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