Gestational arsenic exposure and paternal intergenerational epigenetic inheritance.
Keiko Nohara1, Takehiro Suzuki1, Kazuyuki Okamura1
1Center for Health and Environmental Risk Research, National Institute for Environmental Studies, Tsukuba 305-8506, Japan.
Toxicology and Applied Pharmacology
|November 8, 2020
Summary
Gestational exposure to arsenic can cause heritable liver tumors in male mice through epigenetic changes in sperm. These effects are passed down paternally across generations.
Area of Science:
- Environmental epigenetics
- Reproductive toxicology
- Intergenerational health
Background:
- Environmental exposures during pregnancy can cause long-term and heritable health effects in offspring.
- Epigenetic modifications (DNA methylation, histone modifications, small RNAs) in sperm can transmit acquired phenotypes across generations.
- Arsenic is a known environmental toxicant with potential to disrupt normal development.
Purpose of the Study:
- To investigate the paternal intergenerational and transgenerational effects of gestational arsenic exposure.
- To examine epigenetic alterations, specifically DNA methylation, in offspring tumors and sperm following maternal arsenic exposure.
- To identify potential molecular targets responsible for arsenic-induced tumor augmentation.
Main Methods:
- Exposure of pregnant mice (F0) to sodium arsenite during gestation.
- Analysis of hepatic tumors in male F2 offspring for DNA methylation changes.
- Investigation of DNA methylation status in sperm from exposed F1 generation mice.
- Comparative analysis of epigenetic modifications between exposed and control groups.
Main Results:
- Gestational exposure to sodium arsenite increased hepatic tumor incidence in male F2 offspring.
- Paternal transmission of tumor-augmenting effects was observed.
- Alterations in DNA methylation patterns were identified in F2 tumors and F1 sperm.
- Specific molecular targets potentially mediating these effects were discussed.
Conclusions:
- Gestational arsenic exposure can induce heritable epigenetic changes leading to increased tumor susceptibility in male offspring.
- Sperm epigenome plays a crucial role in transmitting environmentally acquired health risks across generations.
- Further research is needed to fully elucidate the mechanisms and long-term health consequences of arsenic exposure.
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