Gestational Exposure to Ethane Dimethanesulfonate: DISCUSSION(1)


Although indices of normal sexual development such as AGD and time to preputial separation were altered, these changes most likely were due, not to compromised fetal T production, but rather to the EDS-induced decrease in body weight of the male offspring. Fetal whole-body and serum T values in normal male mice were consistent with previous reports, showing an increase between GD 12.5 and 16.5, with a peak in plasma T levels at GD 16.5, just prior to a marked drop on the last day before parturition. Gestational exposure to EDS from GD 11-17 resulted in a diminished fetal T peak in male offspring and associated alterations in testis development and reproductive competence in the adult.

Our results are consistent with literature, suggesting that mouse LCs are less sensitive to the cytotoxicity of EDS than rat LCs because fetal LCs were not destroyed following exposure as evidenced by their presence in histological sections. Moreover, these fetal LCs were still producing T, albeit at a reduced level. Although 160 mg/kg EDS was administered to the dams, we did not determine what level of EDS the fetus was exposed to; however, it may have been considerably less.

The trend toward increases in both unstimulated and hCG-stimulated T production per milligram prepubertal testis in the EDS-exposed animals suggests that the hypothalamic-pituitary axis may compensate for the reduced levels of fetal T. The significant increase in the hCG-stimulated T production in adult testes from EDS exposed offspring further supports this notion. The increase in adult serum LH levels, despite the absence of significant changes in the serum T levels, suggests that there might be an alteration in the endocrine axis, i.e., changes in feedback regulation at the level of the hypothalamus/pituitary. Estimations of testosterone produced per adult LC in control and EDS-exposed males suggest that the LCs in EDS-exposed males are hyperstimulated. We estimated 40- and 5-fold increases in testosterone production per LC under unstimulated and hCG-stimulated conditions, respectively, in EDS-exposed males.

Category: Dimethanesulfonate

Tags: Leydig cells, testis, testosterone, toxicology