Genetic variation in physiological sensitivity to estrogen in mice^Note

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.

Vaginal Heparan Sulfate Linked to Neutrophil Dysfunction in the Acute Inflammatory Response Associated with Experimental Vulvovaginal Candidiasis

“…C3H/HeN mice are highly estrogen responsive, as are all other CVVC-S mouse strains previously evaluated (16, 19). CD-1 mice, on the other hand, have significantly reduced estrogen responsiveness (21, 39). Although estrogen hyposensitivity in CD-1 females was not tested in this study, reports by Calderon et al demonstrated that resistance to sustained colonization in CD-1 mice is independent of the C. albicans strain, the commercial mouse supplier, and the major histocompatibility complex (MHC) haplotype (22).…”

The Polybrominated Diphenyl Ether Mixture DE-71 Is Mildly Estrogenic

“…Others have shown that C57BL/6 mice exhibit higher sensitivity to estrogen compared with other strains (Silberberg and Silberberg 1951; Spearow et al 1999, 2001), but BALB/c mice were not included in those comparisons. Although our findings may illustrate a real difference in estrogen sensitivity between the BALB/c and C57BL/6 strains, an alternative explanation is that between-assay variability makes it difficult to measure small estrogenic effects (Ashby et al 2004; Thigpen et al 2002; Tinwell et al 2000).…”

Comparative effects of neonatal diethylstilbestrol on external genitalia development in adult males of two mouse strains with differential estrogen sensitivity

“…Since then evidence has demonstrated strain-specific variability in response to estrogen for a variety of endpoints in both female and male mice (Spearow et al, 1999; Spearow and Barkley, 1999; Spearow et al, 2001). Given the essential role of external genitalia (ExG) in reproduction and the known teratogenesis of estrogen on ExG development (Baskin et al, 2001b; Goyal et al, 2007), in the accompanying paper we examined strain-specific differences on ExG development following prenatal treatment with diethylstilbestrol (DES).…”