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Cited by 137Epigenetics and DNA MethylationEffects and risks of endocrine disrupting chemicalsGenetic Syndromes and Imprinting

Deleterious effects of endocrine disruptors are corrected in the mammalian germline by epigenome reprogramming

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Iqbal, Khursheed, Tran, Diana A, Li, Arthur X, Warden, Charles, Bai, Angela Y, Singh, Purnima, Wu, Xiwei, Pfeifer, Gerd P +1 more·2015·Genome Biology
DOI 10.1186/s13059-015-0619-zPMC PMC4376074
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Abstract

Background: Exposure to environmental endocrine-disrupting chemicals during pregnancy reportedly causes transgenerationally inherited reproductive defects. We hypothesized that to affect the grandchild, endocrine-disrupting chemicals must alter the epigenome of the germ cells of the in utero -exposed G1 male fetus. Additionally, to affect the great-grandchild, the aberration must persist in the germ cells of the unexposed G2 grandchild. Results: Here, we treat gestating female mice with vinclozolin, bisphenol A, or di-(2-ethylhexyl)phthalate during the time when global de novo DNA methylation and imprint establishment occurs in the germ cells of the G1 male fetus. We map genome-wide features in purified G1 and G2 prospermatogonia, in order to detect immediate and persistent epigenetic aberrations, respectively. We detect changes in transcription and methylation in the G1 germline immediately after endocrine-disrupting chemicals exposure, but changes do not persist into the G2 germline. Additional analysis of genomic imprints shows no persistent aberrations in DNA methylation at the differentially methylated regions of imprinted genes between the G1 and G2 prospermatogonia, or in the allele-specific transcription of imprinted genes between the G2 and G3 soma. Conclusions: Our results suggest that endocrine-disrupting chemicals exert direct epigenetic effects in exposed fetal germ cells, which are corrected by reprogramming events in the next generation. Avoiding transgenerational inheritance of environmentally-caused epigenetic aberrations may have played an evolutionary role in the development of dual waves of global epigenome reprogramming in mammals.

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  • Studies on transgenerational effects of endocrine disruptors and of high fat diet on the DNA methylome have recently been challenged by others.

    “While most of published studies are technically sound, the majority still await independent confirmation; studies on transgenerational effects of endocrine disruptors and of high fat diet on the DNA methylome have recently been challenged by others10,11.”

    From A critical view on transgenerational epigenetic inheritance in humans (2018) · cites this paper as [10]

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Cited by

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Authors
Iqbal, K., Tran, D. A., Li, A. X., Warden, C., Bai, A. Y., Singh, P., Wu, X., Pfeifer, G. P., & Szabó, P. E.
Affiliations
City Of Hope National Medical Center (US)
Corresponding author
Szabó, Piroska E
ORCID
Venue
Genome Biology
Publisher
Springer Science and Business Media LLC
Published
2015-03-27
Volume
16
Issue
1
Pages
59-59
ISSN
1465-6906 (ISSN-L)
DOI
10.1186/s13059-015-0619-z
PMC
PMC4376074
OpenAlex
W2022131093
Cited by
137
References
2
Citations by year
2026: 3 · 2025: 3 · 2024: 4 · 2023: 9 · 2022: 2 · 2021: 19 · 2020: 13 · 2019: 19 · 2018: 15 · 2017: 18 · 2016: 21 · 2015: 9 · 2014: 1
FWCI
9.12
Type
journal article
Language
en
Open access
Licence
Locations
  • Genome biology (publishedVersion, cc-by)
  • PubMed Central (publishedVersion, cc-by)
  • PubMed (publishedVersion)
Funders
  • National Cancer Institute (P30CA033572)
  • National Institute of General Medical Sciences (R01GM064378)
  • National Institute of Environmental Health Sciences (R01ES015185)
  • Institute of Genetics
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Epigenetics and DNA Methylation
  • Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Syndromes and Imprinting
Keywords
endocrine disruptors, transgenerational epigenetic inheritance, epigenetic reprogramming, germ cells, prospermatogonia, DNA methylation, genomic imprinting, vinclozolin, bisphenol A, DEHP, prenatal chemical exposure, imprinted genes, allele-specific transcription
MeSH terms
Bisphenol A Compounds, Animals, Benzhydryl Compounds, Female, Germ Cells, Male, Oxazoles, Phenols, Pregnancy, Reproduction, Spermatozoa, Genomic Imprinting, DNA Methylation, Epigenesis, Genetic, Mice, Endocrine Disruptors, Cellular Reprogramming

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