Neonatal exposure to herbicide acetochlor alters pubertal development in female wistar rats

Abstract

Objectives: The purpose of this study was to evaluate the effects of neonatal exposure to the herbicide acetochlor (ACT) on pubertal development and reproductive functions in female Wistar rats and to investigate capability of ACT to interfere with estradiol binding to rat uterine estrogen receptors (ERs) ex vivo.

Methods: Acetochlor (7.68 and 15.36 mg/kg/day) was administered by subcutaneous injection from postnatal day (PND) 4–7, and vaginal opening, and estrous cyclicity were evaluated from PND 8-159. A second group of adult ovariectomized female rats was dosed for 6 days with ACT (153.6 mg/kg/day, oral gavage). The interference of ACT with the binding of [³H]Estradiol -17β to uterine nuclear and cytoplasmic estrogen receptors was analyzed ex vivo in receptor binding assay.

Results: Both doses of ACT caused acceleration of the age at eye opening and vaginal patency that were significantly different from the control. In addition, altered estrous cyclicity was observed in the ACT (15.36 mg/kg/day) group with 54% of the female rats displaying irregular cycles at PND 159. While uterine weights were not altered, a significant accumulation of uterine nuclear estrogen receptors was observed in the ACT group.

Conclusion: These results indicate that acetochlor can act as the endocrine disruptor and that endpoints related to pubertal development and reproductive functions sensitive sites are targeted with this persistent pollutant.

Keywords::

• Herbicides
• endocrine disruptors
• estrogen receptor
• estrous cycle
• reproductive toxicity

Acknowledgements

The authors thank J. Bachraty, Bc. from the Slovak Medical University, Bratislava, for his help with the artwork. The authors are indebted to Dr. K. Kahayova for the assistance with the English translation of their manuscript. Especially, the authors would like to thank Dr. Susan C. Laws, National Health and Environmental Effects Research Laboratory, U.S. Environmental Protection Agency for her valuable and inspiring consultations about results of vaginal opening assay and estrous cyclicity.

Declaration of interest

This study was supported by Grant No. 049207 Ministry of Health of Slovak Republic.