The effects of maternal exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin on testicular steroidogenesis in infantile male rats.

Exposure of adult male animals to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) decreases serum androgen concentrations. Reduction in androgen levels after maternal exposure has also been reported, but these results have not been reproduced. We have earlier shown that TCDD stimulates rather than inhibits testosterone synthesis in the prenatal rat testis. The aim of the present study was to elucidate in utero-induced effects of TCDD on testicular steroidogenesis in the 14-day-old infant rats. At that time the foetal Leydig cell population is still the prevailing source of androgens. Pregnant Sprague-Dawley dams were given a single oral dose of TCDD (0, 0.04, 0.2, or 1.0 microg/kg) on day 13 of pregnancy. On postnatal day 14, the body weight of male offspring was reduced after exposure to 1.0 microg/kg TCDD (from 33.9 +/- 1.66 g to 31.6 +/- 2.67 g). Relative testis weight, plasma testosterone, luteinizing hormone and follicle-stimulating hormone levels remained unaltered in all exposure groups. Moreover, in ex vivo incubations, testosterone and cAMP production was not affected. StAR protein level in the freshly isolated testes was increased in the 0.2 microg/kg group, and seminiferous cord diameter in the 0.04 microg/kg group. The present study confirms our earlier findings in in utero TCDD-exposed foetal testis indicating that maternal TCDD exposure does not negatively influence the developmental testosterone production of foetal type Leydig cells in rats.

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

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 microg/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), 3beta-hydroxy-steroid-dehydrogenase/Delta(5)-Delta(4) isomerase type I (3beta-HSD1), P-450 17alpha-hydroxylase/17,20-lyase (P450-17alpha), and cytochrome P-450 aromatase (P450arom) were determined on postnatal days (PND) 10-16. TCDD 1.0 mug/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.

Infantile 4-tert-octylphenol exposure transiently inhibits rat ovarian steroidogenesis and steroidogenic acute regulatory protein (StAR) expression.

Phenolic compounds, such as 4-tert-octylphenol (OP), have been shown to interfere with rat ovarian steroidogenesis. However, little is known about steroidogenic effects of infantile OP exposure on immature ovary. The aim of the present study was to investigate the effects of infantile OP exposure on plasma FSH, LH, estradiol, and progesterone levels in 14-day-old female rats. The effect on ovarian steroidogenic acute regulatory protein (StAR) and FSH receptor (FSHr) expression was analyzed by Western blotting. Ex vivo analysis was carried out for follicular estradiol, progesterone, testosterone, and cAMP production. Sprague-Dawley rats were given OP (0, 10, 50, or 100 mg/kg) subcutaneously on postnatal days 6, 8, 10, and 12. On postnatal day 14, plasma FSH was decreased and progesterone increased significantly at a dose of 100 mg OP/kg. In addition, the highest OP dose advanced the time of vaginal opening in puberty. OP had no effect on infantile LH and estradiol levels or ovarian FSHr content. Ovarian StAR protein content and ex vivo hormone and cAMP production were decreased at all OP doses compared to controls. However, hormone levels recovered independent on FSH and even increased above the control level during a prolonged culture. On postnatal day 35, no statistically significant differences were seen between control and OP-exposed animals in plasma FSH, LH, estradiol, and progesterone levels, or in ovarian StAR protein content. The results indicate that the effect of OP on the infantile ovary is reversible, while more permanent effects in the hypothalamus and pituitary, as described earlier, are involved in the reduction of circulating FSH levels and premature vaginal opening.