Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease

Eric E Nilsson; Matthew D Anway; Jacob Stanfield; Michael K Skinner

doi:10.1530/REP-07-0542

Back

Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease

Journal article

Open access

Peer reviewed

Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease

Eric E Nilsson, Matthew D Anway, Jacob Stanfield and Michael K Skinner

Reproduction (Cambridge, England), Vol.135(5), pp.713-721

05/2008

DOI: https://doi.org/10.1530/REP-07-0542

Handle:

https://hdl.handle.net/2376/105772

PMCID: PMC5703189

PMID: 18304984

Files and links (2)

pdf

Transgenerational epigenetic effects210.93 kBDownload View

Open Access

url

https://doi.org/10.1530/REP-07-0542View

Published (Version of record) Open

Abstract

Prenatal Exposure Delayed Effects

Pregnancy Complications - etiology

Brain Neoplasms - etiology

Breeding

Fungicides, Industrial - toxicity

Maternal Exposure

Rats, Sprague-Dawley

Endocrine Disruptors - toxicity

Toxicity Tests, Chronic

Oxazoles - toxicity

Kidney Neoplasms - etiology

Age of Onset

Epigenesis, Genetic - drug effects

Kidney Diseases - etiology

Pregnancy

Endocrine disruptor exposure during gonadal sex determination was previously found to induce male rat adult onset transgenerational disease (F1-F4 generation), and this was associated with an alteration in the epigenetic (i.e., DNA methylation) programming of the male germ line. The current study was designed to characterize the transgenerational disease phenotypes of the female adult offspring. Pregnant rats (F0 generation) were treated transiently with vinclozolin (i.e., fungicide with anti-androgenic activity) on embryonic (E) days E8-E14 of gestation. F1 control and vinclozolin generation offspring from different litters were mated to produce F2 offspring, and similarly F2 generation animals produced F3 generation offspring. Observations demonstrated that 9 out of 105 pregnant rats (8.6%) from the vinclozolin F1-F3 generations exhibited uterine hemorrhage and/or anemia late in pregnancy. None (0 out of 82) of the control F1-F3 generation females had similar pregnancy problems. Complete blood cell counts and serum chemistry profiles demonstrated that selected vinclozolin generation animals, but not controls, exhibited marked regenerative anemia in late pregnancy. Examination of kidney histology revealed moderate or severe glomerular abnormalities in 67% of the vinclozolin F2 and F3 generation adult females compared with 18% of the controls. Adult female vinclozolin generation animals also developed various types of tumors in 6.5% of the animals (11 out of 170), while 2% of control-line animals (3 out of 151) developed mammary tumors. Observations demonstrate that vinclozolin exposure during gonadal sex determination promotes a transgenerational increase in pregnancy abnormalities and female adult onset disease states.

Metrics

1 File views/ downloads

2 Record Views

See more details

Details

Title: Transgenerational epigenetic effects of the endocrine disruptor vinclozolin on pregnancies and female adult onset disease
Creators: Eric E Nilsson - Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, Washington 99164-4231, USA
Matthew D Anway
Jacob Stanfield
Michael K Skinner
Publication Details: Reproduction (Cambridge, England), Vol.135(5), pp.713-721
Academic Unit: Biological Sciences, School of
Publisher: Bioscientifica Ltd; England
Number of pages: 9
Grant note: R01 HD048898 / NICHD NIH HHS
Identifiers: 99900547257301842
Language: English
Resource Type: Journal article