Transgenerational effects in DNA methylation, genotoxicity and reproductive phenotype by chronic arsenic exposure

Lydia Enith Nava-Rivera,Javier Morán-Martínez,Pilar Carranza-Rosales,Hector Delgado-Aguirre,Nancy Elena Guzmán-Delgado,Nadia Denys Betancourt-Martínez,Rodrigo Lozoya-Martínez,José Omar Zambrano-Ortíz,Irma Edith Carranza-Torres

doi:10.1038/s41598-021-87677-y

Lydia Enith Nava-Rivera, Javier Morán-Martínez + Show 7 more

Open Access

https://doi.org/10.1038/s41598-021-87677-y

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Abstract

An emerging concern is the influences of early life exposure to environmental toxicants on offspring characteristics in later life. Since recent evidence suggests a transgenerational transference of aberrant phenotypes from exposed-parents to non-exposed offspring related to adult-onset diseases including reproductive phenotype. The transgenerational potential of arsenic a well know genotoxic and epigenetic modifier agent has not been assessed in mammals until now. In this experimental study, we evaluated the transgenerational effects of arsenic in a rat model with chronic exposure to arsenic. Rats chronically exposed to arsenic in drinking water (1 mg As2O3/L) (F0) were mated to produce the arsenic lineage (F1, F2, and F3). The arsenic toxic effects on were evaluated over the four generations by analyzing the DNA methylation percentage, genotoxicity in WBC and physical and reproductive parameters, including sperm quality parameters and histopathological evaluation of the gonads. Chronic exposure to arsenic caused genotoxic damage (F0–F3) different methylation patterns, alterations in physical and reproductive parameters, aberrant morphology in the ovaries (F0 and F1) and testicles (F1–F3), and a decrease in the quality of sperm (F0–F3, except F2). Parental chronic arsenic exposure causes transgenerational genotoxicity and changes in global DNA methylation which might be associated with reproductive defects in rats. Combined with recent studies reveal that disturbances in the early life of an individual can affect the health of later generations.

Highlights

Arsenic (As), an omnipresent element in the earth’s crust[1] and a knowing toxicant agent in humans, continues being a research objective since millions of people worldwide are still chronically exposed to arsenicals, mainly through drinking water, keeping it as a major public health p roblem[2]
Species and nitrogen species (ROS/RNS), mechanism by which it can induce a well-known genotoxic effect, besides there is information indicating the relation of As with epigenetic modifications, suggesting the induction of adverse effects to human health, through a key mechanism of gene regulation, the DNA methylation[9,10,11,12,13], which is an heritable epigenetic mechanism that occurs at position 5 of the cytosine residues (5-mC) and ensure the correct packaging of DNA and regulation of gene expression in eukaryotic cells[14], changes in the global methylation status are related to the environment exposition being propose as a potential biomarker of diseases[15]
Arsenic prenatal exposure is inversely associated with infant size at birth in h umans[34, 35], in rodents there is evidence of not bodyweight alterations in p ups[36, 37], besides an evident change in organs weight such as kidney, liver, epididymis and gonads[38,39,40]

Summary

Introduction

Arsenic (As), an omnipresent element in the earth’s crust[1] and a knowing toxicant agent in humans, continues being a research objective since millions of people worldwide are still chronically exposed to arsenicals, mainly through drinking water, keeping it as a major public health p roblem[2]. An emerging concern is the consequences of As early-life exposure since there is evidence of adverse effects of gestational or even earlier exposure in parents’ life (F0 generation) to diverse environmental toxicants, can lead to adult onset disease in the offspring (F1 generation) or in a multigenerational (F2 generation) or transgenerational way (F3 and beyond)[3,4,5]. The mechanisms that participate in this developmental programming in which early life exposure may affect the later-life are in continuous researching, this is really important since, besides the genotoxicity caused by some environmental toxicants, these can generate epigenetics changes that can regulate gene expression and be transgenerationally transmitted[6]. We investigated the transgenerational reproductive effects of As in drinking water exposition through a rodent design based in the expose populations: with an early-life and chronical parental exposure (F0 generation). The evaluation of the potential of As to cause changes in DNA methylation and genotoxicity over generations (F0–F3)

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