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ToxSci Advance Access published online on August 13, 2004
Toxicological Sciences, doi:10.1093/toxsci/kfh251
Toxicological Sciences © Society of Toxicology 2004; all rights reserved
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Received May 31, 2004
Accepted August 6, 2004

Reproductive and Developmental Toxicology

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 1*, Saske Hoving 1, Johannes H. J. van den Berg 1, Bert M. Weijers 2, Hans J. Swarts 3, Eline M. van der Beek 3, Åke Bergman 4, Jan H. Koeman 1, Abraham Brouwer 5

1 Toxicology Group, Wageningen University, Wageningen, The Netherlands
2 Laboratory Animal Center, Wageningen University, The Netherlands
3 Department of Animal Physiology, Haarweg 10, 6709 PJ, Wageningen University, The Netherlands
4 Department of Environmental Chemistry, Wallenberg Laboratory, Stockholm University, Stockholm, Sweden
5 Toxicology Group, Wageningen University, Wageningen The Netherlands; Institute of Environmental Studies, Vrije Universiteit, Amsterdam, The Netherlands

* To whom correspondence should be addressed. E-mail: ilonka.meerts{at}notox.nl.


  Abstract

Previous studies 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 gestation days 10 to 16. In this study, the effects of 4-OH-CB-107 on developmental landmarks, steroid hormone levels and estrous cyclicity of rat offspring following 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 gestation days 10 to 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 neurobehaviour following exposure to 4-OH-CB107 will be reported elsewhere.

Keywords: estrous cycle; anogenital distance; PCB; metabolite; reproductive senescence.
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