Developmental effects of an environmental antiandrogen: the fungicide vinclozolin alters sex differentiation of the male rat
Abstract
In humans and rodents, exposure to hormonally active chemicals during sex differentiation can produce a wide range of abnormal sexual phenotypes including masculinized and defeminized females and feminized and demasculinized males. Although numerous "environmental estrogens," including pesticides, toxic substances (PCBs), and plant and fungal estrogens, have been shown to alter mammalian sex differentiation, similar information on environmental androgens is lacking. Recently, the fungicide vinclozolin (V) was found to inhibit sexual differentiation in male rats in an antiandrogenic manner. In the present study, V was administered to pregnant rats (p.o.) at 0, 100, or 200 mg/kg/day in corn oil during the period of sex differentiation (Gestational Day 14 to Postnatal Day 3) to examine the demasculinizing effect of this fungicide more closely. In both groups of V-treated male offspring, anogenital distance was female like at birth, and nipple development was prominent at 2 weeks of age. After puberty, most of the V-treated male offspring were unable to attain intromission even though they all mounted sexually receptive females. The V-treated male offspring that appeared to achieve intromission, failed to ejaculate normally, as no sperm were found in the uterus after overnight matings. A factor in the abnormal ejaculation was that all V-treated male offspring had cleft phallus with hypospadias. In addition, a number of unusual reproductive malformations were noted when the males…
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Male fetuses exposed to antiandrogens during perinatal life are permanently demasculinized in their morphology and physiology.
“Male fetuses exposed to antiandrogens during perinatal life are permanently demasculinized in their morphology and physiology, whereas exposure to exogenous androgens permanently masculinizes females.”
From Androgens and environmental antiandrogens affect reproductive development and play behavior in the Sprague-Dawley rat. (2002) · cites this paper as Gray et al. 1994
Perinatal exposure to Vz reduces seminal vesicle and ventral prostate weights in adult male rats.
“adult male rats have reduced anogenital distances (AGDs), reduced seminal vesicle and ventral prostate weights, and lower epididymal sperm counts after perinatal exposure to Vz (Gray et al. 1994; Hellwig 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 Gray et al. 1994
Adult male rats exposed to perinatal Vz will mount sexually receptive females but are unable to achieve vaginal penetration, suggesting an underlying erectile dysfunction.
“Gray et al. (1994) have shown that adult male rats exposed to perinatal Vz will mount sexually receptive females but are unable to achieve vaginal penetration, suggesting that there is an underlying erectile dysfunction.”
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 Gray et al. (1994)
Perinatal exposure to Vz lowers epididymal sperm counts in adult male rats.
“adult male rats have reduced anogenital distances (AGDs), reduced seminal vesicle and ventral prostate weights, and lower epididymal sperm counts after perinatal exposure to Vz (Gray et al. 1994; Hellwig 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 Gray et al. 1994
Perinatal exposure to Vz reduces anogenital distance in adult male rats.
“adult male rats have reduced anogenital distances (AGDs), reduced seminal vesicle and ventral prostate weights, and lower epididymal sperm counts after perinatal exposure to Vz (Gray et al. 1994; Hellwig 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 Gray et al. 1994
High doses of Vz are associated with measures of gross toxicity such as lowered body weights and increased mortality rate due to granulomas and bladder stones.
“High doses are associated with measures of gross toxicity such as lowered body weights and increased mortality rate due to granulomas and bladder stones (Gray et al. 1994; Hellwig 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 Gray et al. 1994
In earlier investigations, during copulation, exposed males mounted but were unable to achieve vaginal penetration.
“during copulation, exposed males mounted but were unable to achieve vaginal penetration (Gray et al. 1994).”
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 Gray et al. 1994
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“Prominent examples of AR antagonists are the pharmacologic agent flutamide as well as the fungicide vinclozolin (Gray et al. 1994, 1999; ImperatoMcGinley et al. 1992).”
BackgroundInfluentialSelf-citationColbert, 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
“For example, adult male rats have reduced anogenital distances (AGDs), reduced seminal vesicle and ventral prostate weights, and lower epididymal sperm counts after perinatal exposure to Vz (Gray et al. 1994; Hellwig et al. 2000).”
BackgroundInfluentialDias, G. R. M., Giusti, F. C. V., de Novais, C. O., de Oliveira, M. A. L., Paiva, A. G., Kalil-Cutti, B., Mahoney, M. M., & Graceli, J. B. (2025) · Frontiers in Endocrinology · doi:10.3389/fendo.2025.1571689 · Cited by 14 · see citing works
- Authors
- Gray, L. E., Ostby, J. S., & Kelce, W. R.
- Affiliations
- Environmental Protection Agency (US)
- ORCID
- Gray, L.E.
- Venue
- Toxicology and Applied Pharmacology
- Publisher
- Elsevier BV
- Published
- 1994-11
- Volume
- 129
- Issue
- 1
- Pages
- 46-52
- ISSN
- 0041-008X (ISSN-L)
- OpenAlex
- W2032757820
- Cited by
- 491
- References
- 0
- Citations by year
- 2026: 2 · 2025: 12 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 10 · 2020: 4 · 2019: 11 · 2018: 9 · 2017: 7 · 2016: 15 · 2015: 19 · 2014: 17 · 2013: 12 · 2012: 15
- FWCI
- 10.19
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Toxicology and Applied Pharmacology (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, fungicides, androgen receptor antagonists, sexual differentiation, male reproductive tract malformations, hypospadias, testicular descent, anogenital distance, ejaculatory dysfunction, bladder stones, hydronephrosis, developmental toxicity, prenatal exposure, environmental endocrine disruptors
- MeSH terms
- Administration, Oral, Analysis of Variance, Androgen Antagonists, Animals, Body Weight, Computer Simulation, Ejaculation, Endocrine Glands, Environmental Pollutants, Female, Embryonic and Fetal Development, Fungicides, Industrial, Genitalia, Male, Oxazoles, Phenotype, Pregnancy, Prenatal Exposure Delayed Effects, Random Allocation, Sex Differentiation, Sexual Maturation, Rats
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