PUBLICATION
Paternal Inheritance of Bisphenol A Cardiotoxic Effects: The Implications of Sperm Epigenome
- Authors
- Lombó, M., Herráez, M.P.
- ID
- ZDB-PUB-210307-24
- Date
- 2021
- Source
- International Journal of Molecular Sciences 22(4): (Journal)
- Registered Authors
- Keywords
- bisphenol A, heart development, histone acetylation, paternal exposure, sperm epigenome
- MeSH Terms
-
- Acetylation
- Animals
- Benzhydryl Compounds/toxicity*
- Cardiotoxicity/genetics*
- Catechin/analogs & derivatives
- Catechin/pharmacology
- Embryo, Nonmammalian/metabolism
- Epigenesis, Genetic/drug effects
- Epigenome/drug effects
- Epigenome/genetics*
- Histones/metabolism
- Male
- Paternal Inheritance/genetics*
- Phenols/toxicity*
- Spermatozoa/drug effects
- Spermatozoa/metabolism*
- Transcriptome/genetics
- Zebrafish/embryology
- Zebrafish/genetics
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- PubMed
- 33672782 Full text @ Int. J. Mol. Sci.
- CTD
- 33672782
Citation
Lombó, M., Herráez, M.P. (2021) Paternal Inheritance of Bisphenol A Cardiotoxic Effects: The Implications of Sperm Epigenome. International Journal of Molecular Sciences. 22(4):.
Abstract
Parental exposure to bisphenol A (BPA) has been linked to a greater incidence of congenital diseases. We have demonstrated that BPA induces in zebrafish males an increase in the acetylation of sperm histones that is transmitted to the blastomeres of the unexposed progeny. This work is aimed to determine whether histone hyperacetylation promoted by paternal exposure to BPA is the molecular mechanism underlying the cardiogenesis impairment in the descendants. Zebrafish males were exposed to 100 and 2000 µg/L BPA during early spermatogenesis and mated with non-exposed females. We analyzed in the progeny the expression of genes involved in cardiogenesis and the epigenetic profile. Once the histone hyperacetylation was confirmed, treatment with epigallocatechin gallate (EGCG), an inhibitor of histone acetyltransferases, was assayed on F1 embryos. Embryos from males exposed to 2000 µg/L BPA overexpressed the transcription factor hand2 and the receptor esr2b, showing their own promoters-as well as that of kat6a-an enrichment in H3K9ac. In embryos treated with EGCG, both gene expression and histone acetylation (global and specific) returned to basal levels, and the phenotype was recovered. As shown by the results, the histone hyperacetylated landscape promoted by BPA in the sperm alters the chromatin structure of the progeny, leading to the overexpression of the histone acetyltransferase and genes involved in cardiogenesis.
Genes / Markers
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Orthology
Engineered Foreign Genes
Mapping