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Published on: June 7, 2012
Genetic variation in physiological sensitivity to estrogen in mice
J L Spearow1, P O'Henley, P Doemeny
1Section of Neurobiology, Physiology and Behavior, University of California at Davis, 95616, USA. jlspearow@ucdavis.edu
Abstract:
Genetic variation in susceptibility to endocrine disruption by estrogenic agents was examined in juvenile male mice. Mice were implanted with increasing doses of estradiol (E2) at 3 weeks of age and reproductive responses were determined 3 weeks later. Greater than 16-fold differences in susceptibility to the disruption of reproductive development by E2 were detected between strains of mice. CD-1 was much more resistant to the inhibition of testes weight, vesicular gland weight and spermatogenesis by increasing doses of E2. Spermatid maturation was eliminated by low doses of E2 in unselected strains such as C17/Jls and C57BL/6J. In contrast, widely used, large litter size selected CD-1 mice showed little or no inhibition in spermatogenesis even in response to 16-fold higher doses of E2. Testicular sulfotransferase activity (EST) per gram body weight was 3.5-fold higher in untreated CD-1 than in B6 strain males. This suggests that genetic differences in testicular EST activity may play a critical role in the detoxification of estrogens. These and other findings emphasize the need to identify and study genetic variation in sensitivity to estrogen in laboratory animal models used to assess the risk of xenobiotic estrogen exposure.
Insights
Genetic variation significantly impacts how mice respond to estrogenic compounds. CD-1 mice show resistance to reproductive disruption, unlike other strains, due to higher detoxification enzyme activity.
Area of Science:
- Endocrinology
- Toxicology
- Genetics
Background:
- Endocrine-disrupting chemicals (EDCs) pose risks to reproductive health.
- Estrogenic agents can disrupt normal development.
- Understanding genetic variation in sensitivity is crucial for risk assessment.
Purpose of the Study:
- To investigate genetic differences in susceptibility to estrogenic endocrine disruption in male mice.
- To identify mouse strains with varying sensitivity to estradiol (E2).
Main Methods:
- Juvenile male mice of different strains were exposed to increasing doses of estradiol (E2).
- Reproductive parameters including testes weight, vesicular gland weight, and spermatogenesis were assessed.
- Testicular estrone sulfotransferase (EST) activity was measured.
Main Results:
- Significant (greater than 16-fold) differences in E2 susceptibility were observed between mouse strains.
- CD-1 mice were highly resistant to E2-induced inhibition of reproductive parameters.
- Low doses of E2 eliminated spermatid maturation in C17/Jls and C57BL/6J strains.
- CD-1 mice exhibited higher testicular EST activity, suggesting a role in estrogen detoxification.
Conclusions:
- Genetic variation profoundly influences sensitivity to estrogenic endocrine disruption.
- Higher testicular EST activity in CD-1 mice contributes to their resistance.
- Future studies should consider genetic background in animal models for EDC risk assessment.
