Dichlorodiphenyltrichloroethane metabolites inhibit DNMT1 activity which confers methylation-specific modulation of the sex determination pathway

Hu, Junjie; Yang, Yan; Lv, Xiaomei; Lao, Zhilang; Yu, Lili

doi:10.1016/j.envpol.2021.116828

Cited by 6 publications

(1 citation statement)

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“…As studied by Song and colleagues, rat exposure to p,p′-DDE during pregnancy can lead to hypomethylation of IGF2 in sperm, causing an alteration of testicular histology and male fertility [ 73 ]. In addition, a recent human study showed that two other metabolites of DDT (2,2-bis(p-chlorophenyl)-acetic acid (DDA) and 1-chloro-2,2-bis-(p-chlorophenyl) ethylene (DDMU)) can interfere with the DNMT1 activity by binding to it and modifying its catalytic domain conformation, resulting in genomic hypomethylation and alteration of the methylation level of the sexual development genes promoters and of the expression of the Sox9 and Oct4 genes in the embryo, with probable negative influence on offspring survival and health [ 74 ].…”

Section: Link Between Toxicants Exposure Dna Methylation and Biologic...mentioning

confidence: 99%

Evolutionary Implications of Environmental Toxicant Exposure

et al. 2022

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Homo sapiens have been exposed to various toxins and harmful compounds that change according to various phases of human evolution. Population genetics studies showed that such exposures lead to adaptive genetic changes; while observing present exposures to different toxicants, the first molecular mechanism that confers plasticity is epigenetic remodeling and, in particular, DNA methylation variation, a molecular mechanism proposed for medium-term adaptation. A large amount of scientific literature from clinical and medical studies revealed the high impact of such exposure on human biology; thus, in this review, we examine and infer the impact that different environmental toxicants may have in shaping human evolution. We first describe how environmental toxicants shape natural human variation in terms of genetic and epigenetic diversity, and then we describe how DNA methylation may influence mutation rate and, thus, genetic variability. We describe the impact of these substances on biological fitness in terms of reproduction and survival, and in conclusion, we focus on their effect on brain evolution and physiology.

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Section: Link Between Toxicants Exposure Dna Methylation and Biologic...mentioning

confidence: 99%