Effects of in utero exposure to 4-hydroxy-2,3,3',4',5-pentachlorobiphenyl (4-OH-CB107) on developmental landmarks, steroid hormone levels, and female estrous cyclicity in rats

Ilonka A T M Meerts*, Saske Hoving, Johannes H J van den Berg, Bert M Weijers, Hans J Swarts, Eline M van der Beek, Ake Bergman, Jan H Koeman, Abraham Brouwer

*Corresponding author for this work

Research output: Contribution to journalArticleAcademicpeer-review

56 Citations (Scopus)

Abstract

Previous studies have revealed that one of the major metabolites of PCBs detected in human blood, 4-OH-2,3,3',4',5-pentaCB (4-OH-CB107), accumulated in fetal liver, brain, and plasma and reduced maternal and fetal thyroid hormone levels after prenatal exposure to pregnant rats from gestational days (GD) 10-16. In the present study, the effects of 4-OH-CB-107 on developmental landmarks, steroid hormone levels, and estrous cyclicity of rat offspring after in utero exposure to 4-OH-CB107 was investigated. Pregnant rats were exposed to 0, 0.5, and 5.0 mg 4-OH-CB107 per kg bw from GD 10 to GD 16. Another group of rats was exposed to Aroclor 1254 (25 mg/kg bw) to study the differences between effects caused by parent PCB congeners and the 4-OH-CB107 alone. A significant, dose-dependent prolongation of the estrous cycle was observed in 75% and 82% of female offspring exposed to 0.5 and 5.0 mg 4-OH-PCB107, respectively, compared to 64% of Aroclor 1254 (25 mg/kg) exposed offspring. The diestrous stage of the estrous cycle was prolonged, resembling a state of pseudopregnancy, which might reflect early signs of reproductive senescence. Plasma estradiol concentrations in female rat offspring were significantly increased (50%) in the proestrous stage after exposure to 5 mg 4-OH-CB107 per kg bw. No effects on estradiol levels were observed in Aroclor 1254 treated animals. These results indicate that in utero exposure to 4-OH-CB107 leads to endocrine-disrupting effects, especially in female offspring. The possible impact on neurobehavior following exposure to 4-OH-CB107 will be reported elsewhere.

Original languageEnglish
Pages (from-to)259-267
Number of pages9
JournalToxicological Sciences
Volume82
Issue number1
DOIs
Publication statusPublished - Nov-2004

Keywords

  • Administration, Oral
  • Animals
  • Aroclors/administration & dosage
  • Dose-Response Relationship, Drug
  • Estradiol/blood
  • Estrous Cycle/drug effects
  • Female
  • Genitalia/drug effects
  • Male
  • Maternal Exposure
  • Polychlorinated Biphenyls/administration & dosage
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Rats
  • Rats, Wistar
  • Sexual Maturation/drug effects

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