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

TitleIntergenerational response to the endocrine disruptor vinclozolin is influenced by maternal genotype and crossing scheme.
Publication TypeJournal Article
Year of Publication2018
AuthorsPietryk, Edward W., Kiristin Clement, Marwa Elnagheeb, Ryan Kuster, Kayla Kilpatrick, Michael I. Love, and Folami Y. Ideraabdullah
JournalReprod Toxicol
Volume78
Pagination9-19
Date Published2018 06
ISSN1873-1708
KeywordsAnimals, Body Weight, Breeding, DNA Methylation, Endocrine Disruptors, Epigenesis, Genetic, Female, Fungicides, Industrial, Genotype, Male, Maternal-Fetal Exchange, Mice, Inbred C57BL, Mice, Mutant Strains, Oxazoles, Phenotype, Pregnancy, Prenatal Exposure Delayed Effects, Sperm Count, Spermatozoa
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.

DOI10.1016/j.reprotox.2018.03.005
Alternate JournalReprod Toxicol
Original PublicationIntergenerational response to the endocrine disruptor vinclozolin is influenced by maternal genotype and crossing scheme.
PubMed ID29535025
PubMed Central IDPMC5984144
Grant ListP30 ES010126 / ES / NIEHS NIH HHS / United States
K22 ES023849 / ES / NIEHS NIH HHS / United States
T32 ES007018 / ES / NIEHS NIH HHS / United States
P30 ES013508 / ES / NIEHS NIH HHS / United States
P01 CA142538 / CA / NCI NIH HHS / United States
F32 GM085999 / GM / NIGMS NIH HHS / United States
P30 DK056350 / DK / NIDDK NIH HHS / United States
Project: