Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis

Matthew D ANWAY; Stephen S REKOW; Michael K SKINNER

doi:10.1016/j.reprotox.2008.07.008

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Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis

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Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis

Matthew D ANWAY, Stephen S REKOW and Michael K SKINNER

Reproductive toxicology (Elmsford, N.Y.), Vol.26(2), pp.100-106

2008

DOI: https://doi.org/10.1016/j.reprotox.2008.07.008

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https://hdl.handle.net/2376/107639

PMCID: PMC5703191

PMID: 18762243

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Abstract

Fundamental and applied biological sciences. Psychology

Biological and medical sciences

Medical sciences

Embryology: invertebrates and vertebrates. Teratology

Teratology. Teratogens

Toxicology

Exposure of gestating female rats to the anti-androgenic endocrine disruptor vinclozolin has been shown to induce transgenerational adult onset disease phenotypes. The current study, was designed to compare the actions of vinclozolin to the known anti-androgenic compound flutamide. The gestating female rats were exposed to intraperitoneal injections during embryonic day 8-14 (E8-E14) to 100 mg/kg/day vinclozolin or flutamide at either 5 mg or 20 mg/kg/day. As previously observed, vinclozolin induced a transgenerational testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm number. In contrast, the flutamide exposures resulted in a testis phenotype of increased spermatogenic cell apoptosis and decreased epididymal sperm numbers in the F1 generation only, and not the F2 and F3 generation adult males. Interestingly, some of the low dose (5 mg/kg) flutamide F2 generation offspring developed spinal agenesis and supernummery, development (polymelia) of limbs. Although the actions of vinclozolin and flutamide appear similar in the F1 generation males, the transgenerational effects of vinclozolin do not appear to be acting through the same anti-androgenic mechanism as flutamide. (C) 2008 Elsevier Inc. All rights reserved.

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Title: Comparative anti-androgenic actions of vinclozolin and flutamide on transgenerational adult onset disease and spermatogenesis
Creators: Matthew D ANWAY - Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4234, United States
Stephen S REKOW - Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4234, United States
Michael K SKINNER - Center for Reproductive Biology, School of Molecular Biosciences, Washington State University, Pullman, WA 99164-4234, United States
Publication Details: Reproductive toxicology (Elmsford, N.Y.), Vol.26(2), pp.100-106
Academic Unit: Biological Sciences, School of
Publisher: Elsevier; New York, NY
Number of pages: 7
Grant note: National Institute of Environmental Health Sciences; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Environmental Health Sciences (NIEHS) NIH; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA R01HD034707 / EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH &HUMAN DEVELOPMENT; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH Eunice Kennedy Shriver National Institute of Child Health & Human Development (NICHD)
Identifiers: 99900547127701842
Language: English
Resource Type: Accepted manuscript