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Effect of Simazine on pubertal development and thyroid function in the female Wistar rat
Citation:
Zorrilla, L. M., E. K. Gibson, AND T. E. STOKER. Effect of Simazine on pubertal development and thyroid function in the female Wistar rat. Presented at Society for the Study of Reproduction, Kona, HI, May 27 - 30, 2008.
Impact/Purpose:
Presentation at SSR
Description:
Simazine is a chlorotriazine used to control broadleaf weeds, and is one of the most widely used herbicides in the United States. Studies with similar chlorotriazines (atrazine and its metabolites) have demonstrated a disruption in estrous cycle regularity by decreasing the ovulatory surge of luteinizing hormone (LH). However the effects of simazine in the female pubertal rat have not been well studied. The purpose of this study was to assess the effects of simazine on pubertal development and thyroid function in the female rat. The rats were exposed to 0, 12.5, 25, 50 or 100 mg/kg of simazine by oral gavage from postnatal day (PND) 23 to 42. Vaginal opening (VO, a marker of pubertal development) was examined beginning on PND 27, and vaginal smears were obtained from the day of VO until necropsy. Rats were necropsied on PND 42 and reproductive tissue and organ weights were recorded. Serum was collected at necropsy for hormonal analysis of estradiol (E2), LH and thyroxin (T4). No effects of simazine were observed on terminal body weight, liver weight or kidney weight. Simazine significantly decreased pituitary weights at 100 mg/kg, but no effects were seen on ovarian or uterine weights. Simazine significantly delayed VO and age at first estrus at 25 (2.3 days) and 100 (4.0 days) mg/kg. Serum LH and estradiol concentrations on PND 42 were not different from controls. However, simazine did significantly decrease T4 at 100 mg/kg (no effect level, NOEL 50mg/kg), suggesting that simazine may cause disruption of thyroid function. Additionally, adrenal weights were dose-dependently decreased, significant at 50 and 100 mg/kg (NOEL 25 mg/kg). In summary, these results demonstrate that simazine delays VO and age at first estrus, suggesting that it can delay pubertal development in the female rat. Further studies are underway to better characterize the effects of simazine on pubertal onset and to examine the long-term effects of simazine on estrous cyclicity and the LH surge.