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
N1 - Publisher Copyright:
© 2019
PY - 2019/8
Y1 - 2019/8
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
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U2 - 10.1016/j.chemosphere.2019.04.092
DO - 10.1016/j.chemosphere.2019.04.092
M3 - Article
C2 - 31059956
AN - SCOPUS:85065037460
SN - 0045-6535
VL - 228
SP - 586
EP - 594
JO - Chemosphere
JF - Chemosphere
ER -