Paternal BPA exposure in early life alters Igf2 epigenetic status in sperm and induces pancreatic impairment in rat offspring.

Abstract

Exposure to endocrine disruptors in utero appears to alter epigenetics in the male germ-line and subsequently promote adult-onset disease in subsequent generations. Fetal exposure to bisphenol A (BPA), a highly prevalent endocrine disruptor in environment, has been shown to alter epigenetic modification and result in glucose intolerance in adulthood. However, whether fetal exposure to BPA can induce epigenetic modification and phenotypic changes in their subsequent offspring are still unclear. The present study was designed to investigate whether exposure to BPA in early life induced glucose intolerance in the offspring through male germ line, and the underlying epigenetic molecular basis. F0 pregnant SD rats were received corn oil or 40 μg/kg/day of BPA during gestation and lactation. F1 male rats were maintained to generate F2 offspring by mating with untreated female rats. Both the F1 rats after weaning and the F2 offspring were not received any other treatments. Our results showed that male F2 offspring in the BPA group exhibited glucose intolerance and β-cell dysfunction. Decreased expression of Igf2 and associated hypermethylation of Igf2 were observed in islets of male F2 offspring. In addition, similar effects were observed in female F2 animals, but the effects were more pronounced in males. Moreover, abnormal expression and methylation of Igf2 was observed in sperm of adult F1 male rats, indicating that epigenetic modification in germ cells can be partly progressed to the next generation. Overall, our study suggests that BPA exposure during early life can result in generational transmission of glucose intolerance and β-cell dysfunction in the offspring through male germ line, which is associated with hypermethylation of Igf2 in islets. The changes of epigenetics in germ cells may contribute to this generational transmission.

• Authors: Zhenxing Mao, Wei Xia, Huailong Chang, Wenqian Huo, Yuanyuan Li, Shunqing Xu
• Journal: Toxicology letters (Toxicol Lett) Vol. 238 Issue 3 Pg. 30-8 (Nov 04 2015) ISSN: 1879-3169 [Electronic] Netherlands
• PMID: 26276081 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.

Chemical References

• Air Pollutants, Occupational
• Benzhydryl Compounds
• Blood Glucose
• Igf2 protein, rat
• Insulin
• Phenols
• Insulin-Like Growth Factor II
• DNA
• bisphenol A

Topics

• Air Pollutants, Occupational (toxicity)
• Animals
• Benzhydryl Compounds (toxicity)
• Blood Glucose (drug effects, metabolism)
• DNA (genetics)
• Epigenesis, Genetic (drug effects)
• Female
• Glucose Intolerance (chemically induced, genetics)
• Insulin
• Insulin-Like Growth Factor II (genetics, metabolism)
• Islets of Langerhans (drug effects, metabolism)
• Male
• Pancreatic Diseases (etiology)
• Paternal Exposure (adverse effects)
• Phenols (toxicity)
• Pregnancy
• Rats
• Spermatozoa (drug effects, physiology)