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In utero and lactational exposure to TCDD; steroidogenic outcomes differ in male and female rat pups

S A Myllymäki1, T E Haavisto, L J S Brokken

  • 1Department of Biology, Laboratory of Animal Physiology, University of Turku, Finland.

Toxicological Sciences : an Official Journal of the Society of Toxicology
|September 6, 2005
PubMed

Insights

2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) exposure in utero and via lactation impacts female rat pups more than males. Female pups showed reduced estradiol and ovarian function, while male pups exhibited temporary testosterone increases and resistant testicular development.

Area of Science:

  • Endocrinology
  • Toxicology
  • Reproductive Biology

Background:

  • 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is a potent environmental toxicant known to impair fertility and cause reproductive anomalies in mammals.
  • Sex steroid hormone production exhibits distinct developmental profiles in males and females, suggesting potential sex-specific toxicological effects of TCDD.

Purpose of the Study:

  • To investigate the sex-specific effects of in utero and lactational exposure to TCDD on gonadal steroidogenesis and gonadotropin levels in male and female rat pups.
  • To analyze the impact of TCDD on key steroidogenic enzyme gene expression and hormone levels during early postnatal development.

Main Methods:

  • Rat dams were administered a single oral dose of TCDD on gestational day 13.
  • Plasma hormone levels (testosterone, estradiol, progesterone, FSH, LH) and gonadal mRNA expression of steroidogenic enzymes (StAR, P450scc, 3beta-HSD1, P450-17alpha, P450arom) were measured in pups on postnatal days 10-16.
  • Body weight, relative testis weight, and gonadal histology were assessed.

Main Results:

  • High-dose TCDD (1.0 microg/kg) reduced pup body weight but did not affect testis weight or gonadal histology.
  • Female pups exhibited reduced plasma estradiol, increased FSH, and decreased ovarian mRNA levels for StAR and P450arom, with reduced P450arom activity.
  • Male pups showed transiently elevated testosterone on postnatal day 10, with no significant changes in testicular mRNA levels for steroidogenic enzymes.

Conclusions:

  • Developing testes and male gonadotropin secretion appear resistant to TCDD toxicity.
  • In female pups, TCDD exposure leads to reduced estradiol, impaired ovarian P450arom expression and activity, and elevated FSH, potentially contributing to ovarian dysfunction.
  • These findings highlight the sex-specific vulnerability of developing reproductive systems to TCDD.

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