Characterization of the period of sensitivity of fetal male sexual development to vinclozolin
Abstract
Vinclozolin is a fungicide whose metabolites are androgen receptor (AR) antagonists. Previous work in our laboratory showed that perinatal administration of vinclozolin to rats results in malformations of the external genitalia, permanent nipples, reduced anogenital distance (AGD), and reduced seminal vesicle, ventral prostate, and epididymal weights. The objectives of this study were to determine the most sensitive period of fetal development to antiandrogenic effects of vinclozolin and to identify a dosing regime that would induce malformations in all of the male offspring. Pregnant rats were dosed with 400 mg vinclozolin/kg/day on either GD 12-13, GD 14-15, GD 16-17, GD 18-19, or GD 20-21, or with corn oil (2.5 ml/kg) from GD 12 through GD 21 (Experiment 1). All 2-day periods in which significant effects were produced were included in an extended dosing period, GD 14 through GD 19, in which pregnant rats were dosed with 200 or 400 mg vinclozolin/kg (Experiment 2). In Experiment 1, significant effects of vinclozolin were observed in rats dosed on gestation days (GD) 14-15, GD 16-17, and GD 18-19, while the most significant effects were observed in rats treated on GD 16-17. These effects include reduced AGD; presence of areolas, nipples, and malformations of the phallus; and reduced levator ani/bulbocavernosus weight. In contrast, ventral prostate weight was reduced only in the GD 18-19 group. The expanded dosing regime (Experiment 2) increased the percentage of male offspri…
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The weight of the adult BC muscle is most sensitive to Vz exposure during the GD16-17 period.
“the weight of the adult BC muscle is the most sensitive to Vz exposure during the GD16–17 period (Wolf et al. 2000)”
From Perinatal Exposure to Low Levels of the Environmental Antiandrogen Vinclozolin Alters Sex-Differentiated Social Play and Sexual Behaviors in the Rat (2005) · cites this paper as Wolf et al. 2000
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Hotchkiss, A. K., Ostby, J. S., Vandenburgh, J. G., & Gray, L. E. (2002) · Environmental Health Perspectives · doi:10.1289/ehp.02110s3435 · Cited by 82 · see citing works
Colbert, N. K. W., Pelletier, N. C., Cote, J. M., Concannon, J. B., Jurdak, N. A., Minott, S. B., & Markowski, V. P. (2005) · Environmental Health Perspectives · doi:10.1289/ehp.7509 · Cited by 60 · see citing works
“However, because differentiation of spinal cord motor neurons continues until PND10 (Mills and Sengelaub 1993) and the weight of the adult BC muscle is the most sensitive to Vz exposure during the GD16–17 period (Wolf et al. 2000), it is likely that the toxic window for Vz on erectile function spans the GD16–PND10 per…”
Background
- Authors
- Wolf, C. J.
- Affiliations
- Environmental Protection Agency (US)
- Corresponding author
- Wolf, C. J.
- ORCID
- Wolf, C. J.
- Venue
- Toxicological Sciences
- Publisher
- Oxford University Press (OUP)
- Published
- 2000-05-01
- Volume
- 55
- Issue
- 1
- Pages
- 152-161
- ISSN
- 1096-0929 (ISSN-L)
- OpenAlex
- W2130235559
- Cited by
- 168
- References
- 0
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 2 · 2023: 5 · 2022: 7 · 2021: 5 · 2020: 6 · 2019: 6 · 2018: 7 · 2017: 3 · 2016: 4 · 2015: 4 · 2014: 6 · 2013: 6 · 2012: 3
- FWCI
- 8.59
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicological Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Environmental Science › Health, Toxicology and Mutagenesis › Effects and risks of endocrine disrupting chemicals
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sexual Differentiation and Disorders
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Pesticide Exposure and Toxicity
- Keywords
- vinclozolin, antiandrogenic effects, androgen receptor antagonists, anogenital distance, ventral prostate, seminal vesicle, levator ani muscle, ectopic testis, fungicide exposure, developmental toxicity, reproductive toxicity, dose-response relationship, prenatal exposure, endocrine disruptors
- MeSH terms
- Androgen Antagonists, Animals, Female, Fertility, Embryonic and Fetal Development, Fungicides, Industrial, Genitalia, Male, Male, Organ Size, Oxazoles, Pregnancy, Prenatal Exposure Delayed Effects, Sexual Maturation, Testis, Weight Gain, Rats, Long-Evans, Rats
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