Paternal benzo[a]pyrene exposure alters the sperm DNA methylation levels of imprinting genes in F0 generation mice and their unexposed F1-2 male offspring

Wenping Zhang, Jia Yang, Yi Lv, Senlin Li, Mei Qiang

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Background: Benzo[a]pyrene (BaP) is an environmental pollutant known to cause teratogenesis. However, the mechanism underlying this teratogenic effect is not fully understood. Recently, the alteration of DNA methylation of imprinting genes has emerged as a specific epigenetic mechanism linking the impact of environmental pollutants on embryonic development to paternal exposures. The aim of this study was to investigate the transgenerational effects of paternal BaP exposure on the imprinting genes in mouse sperm DNA. Methods: Male C57BL/6J mice received BaP (1.0 or 2.5 mg/kg) or olive oil twice a week for 12 weeks. The methylation status of 6 imprinting genes (H19, Meg3, Peg1, Peg3, Igf2 and Snrpn) was examined by bisulfite pyrosequencing of the sperm DNA of BaP-exposed F0 generation and their offspring. Results: BaP exposure reduced the methylation levels in the imprinting genes H19 and Meg3 and increased the methylation levels of Peg1 and Peg3; however, no significant differences was observed for the methylation levels of Igf2 or Snrpn in the sperm DNA. Furthermore, BaP-exposed male mice were mated with unexposed female mice to generate F1-2 generations. The methylation levels of the 6 genes in the sperm DNA from F1-2 offspring showed a similar pattern as that of the F0 male. The effects were attenuated in F1-2 generations. Conclusions: Paternal BaP exposure altered the methylation levels of imprinting genes, implicating that imprinting genes are susceptible to environmental toxicants. Furthermore, a similar alteration was observed in the F1-2 generations although the attenuated in methylation in F2 generation, revealing a potential transgenerational effect. Capsule: Paternal BaP-exposure altered the methylation of the imprinting genes in the F0-F2 generations, implicating the vulnerability of imprinting genes to environmental toxicants.

Original languageEnglish (US)
Pages (from-to)586-594
Number of pages9
JournalChemosphere
Volume228
DOIs
StatePublished - Aug 1 2019

Fingerprint

imprinting
Benzo(a)pyrene
Pyrene
methylation
Methylation
DNA Methylation
pyrene
sperm
Spermatozoa
Genes
Paternal Exposure
DNA
gene
Environmental Pollutants
Teratogenesis
exposure
Olive oil
pollutant
embryonic development
Inbred C57BL Mouse

Keywords

  • Benzo[a]pyrene
  • DNA methylation
  • Genomic imprinting gene
  • Mice
  • Sperm
  • Transgenerational effects

ASJC Scopus subject areas

  • Environmental Engineering
  • Environmental Chemistry
  • Chemistry(all)
  • Pollution
  • Health, Toxicology and Mutagenesis

Cite this

Paternal benzo[a]pyrene exposure alters the sperm DNA methylation levels of imprinting genes in F0 generation mice and their unexposed F1-2 male offspring. / Zhang, Wenping; Yang, Jia; Lv, Yi; Li, Senlin; Qiang, Mei.

In: Chemosphere, Vol. 228, 01.08.2019, p. 586-594.

Research output: Contribution to journalArticle

@article{2855d533beec4db987c9f8637b4bf7e9,
title = "Paternal benzo[a]pyrene exposure alters the sperm DNA methylation levels of imprinting genes in F0 generation mice and their unexposed F1-2 male offspring",
abstract = "Background: Benzo[a]pyrene (BaP) is an environmental pollutant known to cause teratogenesis. However, the mechanism underlying this teratogenic effect is not fully understood. Recently, the alteration of DNA methylation of imprinting genes has emerged as a specific epigenetic mechanism linking the impact of environmental pollutants on embryonic development to paternal exposures. The aim of this study was to investigate the transgenerational effects of paternal BaP exposure on the imprinting genes in mouse sperm DNA. Methods: Male C57BL/6J mice received BaP (1.0 or 2.5 mg/kg) or olive oil twice a week for 12 weeks. The methylation status of 6 imprinting genes (H19, Meg3, Peg1, Peg3, Igf2 and Snrpn) was examined by bisulfite pyrosequencing of the sperm DNA of BaP-exposed F0 generation and their offspring. Results: BaP exposure reduced the methylation levels in the imprinting genes H19 and Meg3 and increased the methylation levels of Peg1 and Peg3; however, no significant differences was observed for the methylation levels of Igf2 or Snrpn in the sperm DNA. Furthermore, BaP-exposed male mice were mated with unexposed female mice to generate F1-2 generations. The methylation levels of the 6 genes in the sperm DNA from F1-2 offspring showed a similar pattern as that of the F0 male. The effects were attenuated in F1-2 generations. Conclusions: Paternal BaP exposure altered the methylation levels of imprinting genes, implicating that imprinting genes are susceptible to environmental toxicants. Furthermore, a similar alteration was observed in the F1-2 generations although the attenuated in methylation in F2 generation, revealing a potential transgenerational effect. Capsule: Paternal BaP-exposure altered the methylation of the imprinting genes in the F0-F2 generations, implicating the vulnerability of imprinting genes to environmental toxicants.",
keywords = "Benzo[a]pyrene, DNA methylation, Genomic imprinting gene, Mice, Sperm, Transgenerational effects",
author = "Wenping Zhang and Jia Yang and Yi Lv and Senlin Li and Mei Qiang",
year = "2019",
month = "8",
day = "1",
doi = "10.1016/j.chemosphere.2019.04.092",
language = "English (US)",
volume = "228",
pages = "586--594",
journal = "Chemosphere",
issn = "0045-6535",
publisher = "Elsevier Limited",

}

TY - JOUR

T1 - Paternal benzo[a]pyrene exposure alters the sperm DNA methylation levels of imprinting genes in F0 generation mice and their unexposed F1-2 male offspring

AU - Zhang, Wenping

AU - Yang, Jia

AU - Lv, Yi

AU - Li, Senlin

AU - Qiang, Mei

PY - 2019/8/1

Y1 - 2019/8/1

N2 - Background: Benzo[a]pyrene (BaP) is an environmental pollutant known to cause teratogenesis. However, the mechanism underlying this teratogenic effect is not fully understood. Recently, the alteration of DNA methylation of imprinting genes has emerged as a specific epigenetic mechanism linking the impact of environmental pollutants on embryonic development to paternal exposures. The aim of this study was to investigate the transgenerational effects of paternal BaP exposure on the imprinting genes in mouse sperm DNA. Methods: Male C57BL/6J mice received BaP (1.0 or 2.5 mg/kg) or olive oil twice a week for 12 weeks. The methylation status of 6 imprinting genes (H19, Meg3, Peg1, Peg3, Igf2 and Snrpn) was examined by bisulfite pyrosequencing of the sperm DNA of BaP-exposed F0 generation and their offspring. Results: BaP exposure reduced the methylation levels in the imprinting genes H19 and Meg3 and increased the methylation levels of Peg1 and Peg3; however, no significant differences was observed for the methylation levels of Igf2 or Snrpn in the sperm DNA. Furthermore, BaP-exposed male mice were mated with unexposed female mice to generate F1-2 generations. The methylation levels of the 6 genes in the sperm DNA from F1-2 offspring showed a similar pattern as that of the F0 male. The effects were attenuated in F1-2 generations. Conclusions: Paternal BaP exposure altered the methylation levels of imprinting genes, implicating that imprinting genes are susceptible to environmental toxicants. Furthermore, a similar alteration was observed in the F1-2 generations although the attenuated in methylation in F2 generation, revealing a potential transgenerational effect. Capsule: Paternal BaP-exposure altered the methylation of the imprinting genes in the F0-F2 generations, implicating the vulnerability of imprinting genes to environmental toxicants.

AB - Background: Benzo[a]pyrene (BaP) is an environmental pollutant known to cause teratogenesis. However, the mechanism underlying this teratogenic effect is not fully understood. Recently, the alteration of DNA methylation of imprinting genes has emerged as a specific epigenetic mechanism linking the impact of environmental pollutants on embryonic development to paternal exposures. The aim of this study was to investigate the transgenerational effects of paternal BaP exposure on the imprinting genes in mouse sperm DNA. Methods: Male C57BL/6J mice received BaP (1.0 or 2.5 mg/kg) or olive oil twice a week for 12 weeks. The methylation status of 6 imprinting genes (H19, Meg3, Peg1, Peg3, Igf2 and Snrpn) was examined by bisulfite pyrosequencing of the sperm DNA of BaP-exposed F0 generation and their offspring. Results: BaP exposure reduced the methylation levels in the imprinting genes H19 and Meg3 and increased the methylation levels of Peg1 and Peg3; however, no significant differences was observed for the methylation levels of Igf2 or Snrpn in the sperm DNA. Furthermore, BaP-exposed male mice were mated with unexposed female mice to generate F1-2 generations. The methylation levels of the 6 genes in the sperm DNA from F1-2 offspring showed a similar pattern as that of the F0 male. The effects were attenuated in F1-2 generations. Conclusions: Paternal BaP exposure altered the methylation levels of imprinting genes, implicating that imprinting genes are susceptible to environmental toxicants. Furthermore, a similar alteration was observed in the F1-2 generations although the attenuated in methylation in F2 generation, revealing a potential transgenerational effect. Capsule: Paternal BaP-exposure altered the methylation of the imprinting genes in the F0-F2 generations, implicating the vulnerability of imprinting genes to environmental toxicants.

KW - Benzo[a]pyrene

KW - DNA methylation

KW - Genomic imprinting gene

KW - Mice

KW - Sperm

KW - Transgenerational effects

UR - http://www.scopus.com/inward/record.url?scp=85065037460&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85065037460&partnerID=8YFLogxK

U2 - 10.1016/j.chemosphere.2019.04.092

DO - 10.1016/j.chemosphere.2019.04.092

M3 - Article

C2 - 31059956

AN - SCOPUS:85065037460

VL - 228

SP - 586

EP - 594

JO - Chemosphere

JF - Chemosphere

SN - 0045-6535

ER -