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ToxSci Advance Access originally published online on September 1, 2005
Toxicological Sciences 2005 88(2):534-544; doi:10.1093/toxsci/kfi308
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© The Author 2005. Published by Oxford University Press on behalf of the Society of Toxicology. All rights reserved. For Permissions, please email: journals.permissions@oupjournals.org

In Utero and Lactational Exposure to TCDD; Steroidogenic Outcomes Differ in Male and Female Rat Pups

S. A. Myllymäki*,{dagger},2, T. E. Haavisto*,2, L. J. S. Brokken{dagger}, M. Viluksela{ddagger}, J. Toppari{dagger},§ and J. Paranko,1

* Department of Biology, Laboratory of Animal Physiology, 20014 University of Turku, Turku, Finland; {dagger} Department of Physiology, University of Turku, 20520 Turku, Finland; {ddagger} Department of Environmental Health, Laboratory of Toxicology, National Public Health Institute, Box 95, 70701 Kuopio, Finland; § Department of Pediatrics, University of Turku, 20520 Turku, Finland; Department of Anatomy, University of Turku, 20520 Turku, Finland

Received June 17, 2005; accepted August 30, 2005

TCDD (2,3,7,8-tetrachlorodibenzo-p-dioxin) has a potency to induce decreased fertility and structural reproductive anomalies in male and female mammals. While the activity profile of sex steroid hormone production distinctly differs in developing males and females, we wanted to analyze sex-specific effects of TCDD introduced in utero and via lactation on gonadal steroidogenesis and gonadotropin levels in male and female rat infant pups. One oral dose of TCDD (0, 0.04, 0.2, or 1.0 µg/kg) was given to dams on gestational day (GD) 13. Plasma testosterone, estradiol, progesterone, follicle stimulating hormone (FSH), luteinizing hormone (LH), and gonadal mRNA levels for steroid acute regulatory protein (StAR), cytochrome P-450 cholesterol side-chain cleavage (P450scc), 3ß-hydroxy-steroid-dehydrogenase/{Delta}5-{Delta}4 isomerase type I (3ß-HSD1), P-450 17{alpha}-hydroxylase/17,20-lyase (P450–17{alpha}), and cytochrome P-450 aromatase (P450arom) were determined on postnatal days (PND) 10–16. TCDD 1.0 µg/kg reduced body weights but did not affect relative testis weight or alter testicular and ovarian histology. Plasma estradiol levels in dams and female pups were reduced on PND 14 and 16. Progesterone levels remained unaltered, and FSH levels were increased in female pups. In males, testosterone levels were elevated on PND 10. Gonadal mRNA levels for StAR and steroidogenic enzymes increased during the postnatal growth. TCDD caused no changes in relatively low testicular mRNA levels. However, significant reductions in StAR and P450arom mRNA levels were seen in PND 14 ovaries, and P450arom activity was decreased in isolated ovarian follicles. We conclude that developing testis and male gonadotropin secretion are resistant to TCDD-induced toxicity. In female pups, reduced estradiol, ovarian P450arom expression and enzyme activity levels, and elevated FSH levels may have a role in the development of ovarian dysfunction reported in TCDD-exposed females.

Key Words: TCDD; steroidogenesis; follicle-stimulating hormone; FSH; luteinizing hormone; LH; mRNA; infant; ovary; testis; rat.


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