Chronic Exposure to Cadmium Induces Differential Methylation in Mice Spermatozoa.
DNA methylation
cadmium
epigenetics
spermatogenesis
Journal
Toxicological sciences : an official journal of the Society of Toxicology
ISSN: 1096-0929
Titre abrégé: Toxicol Sci
Pays: United States
ID NLM: 9805461
Informations de publication
Date de publication:
12 04 2021
12 04 2021
Historique:
pubmed:
24
1
2021
medline:
19
8
2021
entrez:
23
1
2021
Statut:
ppublish
Résumé
Cadmium exposure is ubiquitous and has been linked to diseases including cancers and reproductive defects. Since cadmium is nonmutagenic, it is thought to exert its gene dysregulatory effects through epigenetic reprogramming. Several studies have implicated germline exposure to cadmium in developmental reprogramming. However, most of these studies have focused on maternal exposure, while the impact on sperm fertility and disease susceptibility has received less attention. In this study, we used reduced representation bisulfite sequencing to comprehensively investigate the impact of chronic cadmium exposure on mouse spermatozoa DNA methylation. Adult male C57BL/J6 mice were provided water with or without cadmium chloride for 9 weeks. Sperm, testes, liver, and kidney tissues were collected at the end of the treatment period. Cadmium exposure was confirmed through gene expression analysis of metallothionein-1 and 2, 2 well-known cadmium-induced genes. Analysis of sperm DNA methylation changes revealed 1788 differentially methylated sites present at regulatory regions in sperm of mice exposed to cadmium compared with vehicle (control) mice. Furthermore, most of these differential methylation changes positively correlated with changes in gene expression at both the transcription initiation stage as well as the splicing levels. Interestingly, the genes targeted by cadmium exposure are involved in several critical developmental processes. Our results present a comprehensive analysis of the sperm methylome in response to chronic cadmium exposure. These data, therefore, highlight a foundational framework to study gene expression patterns that may affect fertility in the exposed individual as well as their offspring, through paternal inheritance.
Identifiants
pubmed: 33483743
pii: 6112042
doi: 10.1093/toxsci/kfab002
pmc: PMC8041459
doi:
Substances chimiques
Cadmium
00BH33GNGH
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Langues
eng
Sous-ensembles de citation
IM
Pagination
262-276Subventions
Organisme : NIEHS NIH HHS
ID : P30 ES026529
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES024478
Pays : United States
Organisme : NIEHS NIH HHS
ID : R01 ES031846
Pays : United States
Organisme : NIGMS NIH HHS
ID : T32 GM008169
Pays : United States
Informations de copyright
© The Author(s) 2021. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.
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