Journal Articles

Intergenerational response to the endocrine disruptor vinclozolin is influenced by maternal genotype and crossing scheme

June 21, 2018

Pietryk EW1, Clement K2, Elnagheeb M1, Kuster R2, Kilpatrick K3, Love MI4, Ideraabdullah FY5. Intergenerational response to the endocrine disruptor vinclozolin is influenced by maternal genotype and crossing scheme. Reprod Toxicol. 2018 Jun;78:9-19. doi: 10.1016/j.reprotox.2018.03.005. Epub 2018 Mar 10.

Author information

1 Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, 120 Mason Farm Rd, CB#7264, Chapel Hill, NC 27599, United States.

2 Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC 28081, United States.

3 Department of Biostatistics, Gillings School of Public Health, University of North Carolina at Chapel Hill, 135 Dauer Drive, CB #7420, Chapel Hill, NC 27599, United States.

4 Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, 120 Mason Farm Rd, CB#7264, Chapel Hill, NC 27599, United States; Department of Biostatistics, Gillings School of Public Health, University of North Carolina at Chapel Hill, 135 Dauer Drive, CB #7420, Chapel Hill, NC 27599, United States.

5 Department of Genetics, School of Medicine, University of North Carolina at Chapel Hill, 120 Mason Farm Rd, CB#7264, Chapel Hill, NC 27599, United States; Nutrition Research Institute, University of North Carolina at Chapel Hill, 500 Laureate Way, Kannapolis, NC 28081, United States; Department of Nutrition, Gillings School of Public Health, University of North Carolina at Chapel Hill, 135 Dauer Drive, CB #7461, Chapel Hill, NC 27599, United States. Electronic address: folami@email.unc.edu.

Abstract

In utero exposure to vinclozolin (VIN), an antiandrogenic fungicide, is linked to multigenerational phenotypic and epigenetic effects. Mechanisms remain unclear. We assessed the role of antiandrogenic activity and DNA sequence context by comparing effects of VIN vs. M2 (metabolite with greater antiandrogenic activity) and wild-type C57BL/6 (B6) mice vs. mice carrying mutations at the previously reported VIN-responsive H19/Igf2 locus. First generation offspring from VIN-treated 8nrCG mutant dams exhibited increased body weight and decreased sperm ICR methylation. Second generation pups sired by affected males exhibited decreased neonatal body weight but only when dam was unexposed. Offspring from M2 treatments, B6 dams, 8nrCG sires or additional mutant lines were not similarly affected. Therefore, pup response to VIN over two generations detected here was an 8nrCG-specific maternal effect, independent of antiandrogenic activity. These findings demonstrate that maternal effects and crossing scheme play a major role in multigenerational response to in utero exposures.

 

KEYWORDS:

DNA methylation; Endocrine disruptor; Epigenetic inheritance; Gene-environment; Genomic imprinting; Maternal effect; Vinclozolin

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