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Titolo:
Characterization of the period of sensitivity of fetal male sexual development to vinclozolin
Autore:
Wolf, CJ; LeBlanc, GA; Ostby, JS; Gray, LE;
Indirizzi:
US EPA, Endocrinol Branch, Reprod Toxicol Div, Natl Hlth & Environm Effects Res Lab, Res Triangle Pk, NC 27711 USA US EPA Res Triangle Pk NC USA 27711 es Lab, Res Triangle Pk, NC 27711 USA N Carolina State Univ, Dept Toxicol, Raleigh, NC 27695 USA N Carolina State Univ Raleigh NC USA 27695 Toxicol, Raleigh, NC 27695 USA
Titolo Testata:
TOXICOLOGICAL SCIENCES
fascicolo: 1, volume: 55, anno: 2000,
pagine: 152 - 161
SICI:
1096-6080(200005)55:1<152:COTPOS>2.0.ZU;2-D
Fonte:
ISI
Lingua:
ENG
Soggetto:
ANDROGEN RECEPTOR EXPRESSION; LEVATOR ANI MUSCLE; TESTICULAR DESCENT; ANTIANDROGEN FLUTAMIDE; 5-ALPHA-REDUCTASE INHIBITOR; REPRODUCTIVE-TRACT; UROGENITAL TRACT; SPRAGUE-DAWLEY; MAMMARY-GLAND; IN-UTERO;
Keywords:
vinclozolin; antiandrogen; androgen receptor; male reproductive development; critical period; levator ani; hypospadias; anogenital distance;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
59
Recensione:
Indirizzi per estratti:
Indirizzo: Gray, LE US EPA, Endocrinol Branch, Reprod Toxicol Div, Natl Hlth & Environm Effects Res Lab, MD 72, Res Triangle Pk, NC 27711 USA US EPA MD 72 Res Triangle Pk NC USA 27711 iangle Pk, NC 27711 USA
Citazione:
C.J. Wolf et al., "Characterization of the period of sensitivity of fetal male sexual development to vinclozolin", TOXICOL SCI, 55(1), 2000, pp. 152-161

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 throughGD 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. Theseeffects 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 offspring with genital malformations (> 92%), and retained nipples (100%), further reduced the weight of the ventral prostate, and reduced the weight of theseminal vesicles. In addition, malformations were more severe and includedvaginal pouch and ectopic/undescended testes. The latter was induced only in the 400 mg/kg group. These data indicate that the reproductive system ofthe fetal male rat is most sensitive to antiandrogenic effects of vinclozolin on GD 16 and 17, although effects are more severe and 100% of male offspring are affected with administration of vinclozolin from GD 14 through GD19.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 07/07/20 alle ore 05:16:48