In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) induces genital dysmorphogenesis in the female rat

Jodi A. Flaws, Rebecca J. Sommer, Ellen K. Silbergeld, Richard E. Peterson, Anne N. Hirshfield

Research output: Contribution to journalArticle

Abstract

Recently, Gray and Ostby (Toxicol. Appl. Pharmacol. 133, 285294, 1995) reported that in utero and lactational TCDD exposure causes striking abnormalities in the rat female reproductive system, including reduced fecundity and vaginal threads. The mechanism by which TCDD induces such abnormalities is unknown. Thus, we sought to determine: (1) whether TCDD reduced fecundity by destroying ovarian follicles and (2) whether the vaginal threads resulted from a TCDD-induced developmental defect during embryogenesis or abnormal vaginal opening at puberty. Pregnant Holtzman rats were treated with 1.0 μg TCDD/kg or vehicle by a single oral dose on gestation day (GD) 11, 15, or 18. Female offspring were monitored for vaginal opening and terminated on postnatal days 2, 21, and 42. The reproductive tract was removed and evaluated for structural abnormalities. The number of primordial follicles also was determined for each ovary. TCDD exposure on GD 11, 15, or 18 did not change the day of vaginal opening, affect ovarian morphology, or reduce the number of primordial follicles. However, this exposure induced the cleft clitoris and vaginal thread originally described by Gray and Ostby (1995) in approximately 55-96% and 36-44% of the litters in our study, respectively. Histologically the thread presented as a thick cord of mesenchyme surrounded by epithelial cells. This defect was clearly visible in histological sections at birth and was noted in the closed vaginas of prepubertal animals. These data suggest that in utero and lactational exposure to TCDD does not reduce the size of the primordial follicle pool; however, it induces developmental abnormalities in the vaginal canal.

Original languageEnglish (US)
Pages (from-to)351-362
Number of pages12
JournalToxicology and Applied Pharmacology
Volume147
Issue number2
DOIs
StatePublished - Dec 1997

ASJC Scopus subject areas

  • Toxicology
  • Pharmacology

Fingerprint Dive into the research topics of 'In utero and lactational exposure to 2,3,7,8-tetrachlorodibenzo-p- dioxin (TCDD) induces genital dysmorphogenesis in the female rat'. Together they form a unique fingerprint.

  • Cite this