On‐going consequences of in utero exposure of Pb: An epigenetic perspective

Abstract

Epigenetic modifications by toxic heavy metals are one of the intensively investigated fields of modern genomic research. Among a diverse group of heavy metals, lead (Pb) is an extensively distributed toxicant causing an immense number of abnormalities in the developing fetus via a wide variety of epigenetic changes. As a divalent cation, Pb can readily cross the placental membrane and the fetal blood brain barrier leading to far-reaching alterations in DNA methylation patterns, histone protein modifications, and micro-RNA expression. Over recent years, several human cohorts and animal model studies have documented hypermethylation and hypomethylation of developmental genes along with altered DNA methyl-transferase expression by in utero Pb exposure in a dose-, duration-, and sex-dependent manner. Modifications in the expression of specific histone acetyltransferase enzymes along with histone acetylation and methylation levels have been reported in rodent and murine models.Apart from these, down-regulation and up-regulation of certain microRNAs crucial for fetal development have been shown to be associated with in utero Pb exposure in human placenta samples. All these modifications in the developing fetus during the prenatal and perinatal stages reportedly caused severe abnormalities in early or adult age, such as impaired growth, obesity, autism, diabetes, cardiovascular diseases, risks of cancer development, and Alzheimer's disease. In this review, currently available information on Pb-mediated alterations in the fetal epigenome is summarized. Further research on Pb-induced epigenome modification will help to understand the mechanisms in detail and will enable us to formulate safety guidelines for pregnant women and developing children.

Endothelial Dnmt3a controls placenta vascularization and function to support fetal growth

“…In the same line, the epigenome of embryonic stem cells is dependent on the interplay of active DNA demethylation via TET (Ten-eleven translocation) proteins and re-methylation by DNMTs (Gu et al 2018). On the other hand, global placental DNA hypomethylation has also been associated to air pollution and Pb exposure (Janssen et al 2013; Tasin et al 2022). These studies demonstrate the potentially far-reaching consequences of the dysregulation of single molecules or broad environmental exposures for adequate placental function and fetal nutrition.…”

Effect of lead exposure on histone modifications: A review

“…[40] The altered levels of these markers suggest their potential involvement in latent upregulation of Alzheimer's Disease causing proteins in the brain. [60,108] The recent review by Tasin et al [109] have extensively discussed epigenetic modifications due to in utero and prenatal Pb exposure.…”

“…The recent review by Tasin et al [ 109 ] have extensively discussed epigenetic modifications due to in utero and prenatal Pb exposure. Among the three epigenetic modulators, altered DNA methylation causing non communicable diseases such as autism, impaired growth, neurodegenerative, cardiovascular diseases and risk of developing cancer is extensively reported in vivo studies as well as validated in human cohort.…”

Review of the association between non-coding RNAs and environmental exposure

“…Environmental exposure has been a health threat for a long time. Different kinds of exposure can cause damage to multiple organs and tissues in the human body and increase the risk of many diseases [1,2]. Unappropriated handling of environmental exposure not only caused severe consequences but also lowered the reputation of public health officials [3].…”