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

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

doi:10.1038/s41598-021-87677-y

Cited by 48 publications

(19 citation statements)

References 115 publications

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“…In-utero exposure to sodium arsenite from embryonic day-10 to day-18 at a concentration of 10 ppb induced an increase in leptin levels, and at 42.5 ppm reduced the litter size compared to control mice [137]. Chronic As trioxide exposure to parental male at a dose of 1 mg/L showed genotoxic damage in F0-F3, altered methylation patterns, changes in reproductive parameters, morphological damage in the ovaries (F0 and F1) and testicles (F1-F3), and compromised sperm quality (F0-F3, except F2) [138]. Exposure of sodium arsenite at the dose of 10 mg/L in drinking water to pregnant females from GD1-21 affected body weight and initial sexual development in male pups and relative anogenital distance also showed changes in the expression of SOD1, SOD2, CAT, and GSTK1 gene in male pup rat [139].…”

Section: Pre-natal Arsenic Exposure Induced Male Reproductive Toxicit...mentioning

confidence: 93%

Contemporary Comprehensive Review on Arsenic-Induced Male Reproductive Toxicity and Mechanisms of Phytonutrient Intervention

Rachamalla

Chinthada

Kushwaha

et al. 2022

Toxics

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Arsenic (As) is a poisonous metalloid that is toxic to both humans and animals. Drinking water contamination has been linked to the development of cancer (skin, lung, urinary bladder, and liver), as well as other disorders such as diabetes and cardiovascular, gastrointestinal, neurological, and developmental damage. According to epidemiological studies, As contributes to male infertility, sexual dysfunction, poor sperm quality, and developmental consequences such as low birth weight, spontaneous abortion, and small for gestational age (SGA). Arsenic exposure negatively affected male reproductive systems by lowering testicular and accessory organ weights, and sperm counts, increasing sperm abnormalities and causing apoptotic cell death in Leydig and Sertoli cells, which resulted in decreased testosterone synthesis. Furthermore, during male reproductive toxicity, several molecular signalling pathways, such as apoptosis, inflammation, and autophagy are involved. Phytonutrient intervention in arsenic-induced male reproductive toxicity in various species has received a lot of attention over the years. The current review provides an in-depth summary of the available literature on arsenic-induced male toxicity, as well as therapeutic approaches and future directions.

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Section: Pre-natal Arsenic Exposure Induced Male Reproductive Toxicit...mentioning

confidence: 93%

Contemporary Comprehensive Review on Arsenic-Induced Male Reproductive Toxicity and Mechanisms of Phytonutrient Intervention

Rachamalla

Chinthada

Kushwaha

et al. 2022

Toxics

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show abstract

“…These results indicate a paternal epigenetic influence on adult F1 and F2 offspring metabolic disease phenotypes. Another study exploring both maternal and paternal exposure on transgenerational health found altered DNA methylation and reproductive phenotypes (Nava‐Rivera et al, 2021). Methylation in the ovary and testes was significantly lower in the F1 generation, remained unchanged in the F2 generation, and increased within the F3 generation.…”

Section: Discussionmentioning

confidence: 99%

Intergenerational arsenic exposure on the mouse epigenome and metabolic physiology

Colwell

Flack

Rezabek

et al. 2023

Environ and Mol Mutagen

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Inorganic arsenic (iAs) is one of the largest toxic exposures to impact humanity worldwide. Exposure to iAs during pregnancy may disrupt the proper remodeling of the epigenome of F1 developing offspring and potentially their F2 grand-offspring via disruption of fetal primordial germ cells (PGCs). There is a limited understanding between the correlation of disease phenotype and methylation profile within offspring of both generations and whether it persists to adulthood. Our study aims to understand the intergenerational effects of in utero iAs exposure on the epigenetic profile and onset of disease phenotypes within F1 and F2 adult offspring, despite the lifelong absence of direct arsenic exposure within these generations. We exposed F0 female mice (C57BL6/J) to the following doses of iAs in drinking water 2 weeks before pregnancy until the birth of the F1 offspring: 1, 10, 245, and 2300 ppb. We found sex-and dose-specific changes in weight and body composition that persist from early time to adulthood within both generations. Fasting blood glucose challenge suggests iAs exposure causes dysregulation of glucose metabolism, revealing generational, exposure, and sex-specific differences. Toward understanding the mechanism, genome-wide DNA methylation data highlights exposure-specific patterns in liver, finding dysregulation within genes associated with cancer, T2D, and obesity. We also identified regions containing persistently differentially methylated CpG sites between F1 and F2 generations. Our results indicate the F1 developing embryos and their PGCs, which will result in F2 progeny, retain epigenetic damage established during the prenatal period and are associated with adult metabolic dysfunction.

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“…These results indicate a paternal epigenetic influence on adult F1 and F2 offspring metabolic disease phenotypes. Another study exploring both maternal and paternal exposure on transgenerational health found altered DNA methylation and reproductive phenotypes (Nava-Rivera et al 2021). Methylation in the ovary and testes was significantly lower in the F1 generation, remained unchanged in the F2 generation, and increased within the F3 generation.…”

Section: Discussionmentioning

confidence: 99%

Intergenerational Arsenic Exposure on the Mouse Epigenome and Metabolic Physiology

Colwell

Wanner

Rezabek

et al. 2022

Preprint

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Inorganic Arsenic (iAs) is one of the largest toxic exposures to impact humanity worldwide. Exposure to iAs during pregnancy may disrupt the proper remodeling of the epigenome of F1 developing offspring and potentially their F2 grand-offspring via disruption of fetal primordial germ cells (PGCs). There is a limited understanding between the correlation of disease phenotype and methylation profile within offspring of both generations and whether it persists to adulthood. Our study aims to understand the intergenerational effects of in utero iAs exposure on the epigenetic profile and onset of disease phenotypes within F1 and F2 adult offspring, despite the life-long absence of direct arsenic exposure within these generations. We exposed F0 female mice (C57BL6/J) to the following doses of iAs in drinking water 2 weeks before pregnancy until the birth of the F1 offspring: 1 ppb, 10 ppb, 245 ppb, and 2300 ppb. We found sex- and dose-specific changes in weight and body composition that persist from early time to adulthood within both generations. Fasting blood glucose challenge suggests iAs exposure causes dysregulation of glucose metabolism, revealing generational, exposure, and sex specific differences. Toward understanding the mechanism, genome-wide DNA methylation data highlights exposure-specific patterns in liver, finding dysregulation within genes associated with cancer, T2D, and obesity. We also identified regions containing persistently differentially methylated CpG sites between F1 and F2 generations. Our results indicate F1 developing embryos and F2 PGCs retain epigenetic damage established during the prenatal period and are associated with adult metabolic dysfunction.

show abstract

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

Cited by 48 publications

References 115 publications

Contemporary Comprehensive Review on Arsenic-Induced Male Reproductive Toxicity and Mechanisms of Phytonutrient Intervention

Contemporary Comprehensive Review on Arsenic-Induced Male Reproductive Toxicity and Mechanisms of Phytonutrient Intervention

Intergenerational arsenic exposure on the mouse epigenome and metabolic physiology

Intergenerational Arsenic Exposure on the Mouse Epigenome and Metabolic Physiology

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