Search

It has been known for decades that many students have misguided views about what scientists do, what they look like, and who they are (Barman 1997). Students typically think of [...]

Endocrine disrupting chemicals (EDCs) are pollutants found throughout the environment that disrupt normal endocrine processes. In mice, penis development is thought to be most susceptible to EDCs during a critical developmental window occurring on embryonic days (E) 15.5–17.5. However, androgen signaling begins on E13.5 when androgen receptor (AR) protein is found in the genitalia and testosterone is circulating. We hypothesize that disrupting androgen signaling prior to the established critical window sensitizes the penis to future androgen disruption. To test this hypothesis, CD1 dams were exposed to vinclozolin or a corn oil solvent control on E13.5 and E14.5 and AR levels were measured with immunohistochemistry on E14.5. Early antiandrogen exposure reduced AR within nuclei and decreased intensity of AR expression within E14.5 genitalia. To evaluate the influence of antiandrogen exposure before the known critical window of penis development, two groups of pregnant dams (n = 3) were exposed to vinclozolin starting at either E13.5 or E14.5 and continued exposure through E16.5. Histology and M.O.U.S.E. scoring were used to quantify penis abnormalities. To account for differences in total doses mice experienced due to differences in length of dosing time, we compared animals that received the same total doses. Exposure to antiandrogens on E13.5 exacerbated malformations when exposure was continued through sexually dimorphic development. Both exposure time and vinclozolin dose are important for severity of vinclozolin-induced penis abnormalities in mice. This work shows that antiandrogen exposure prior to sensitive periods can exacerbate the effects of later antiandrogen exposure on reproductive development.Prior to the sensitive window the penis is responsive to antiandrogen exposure, and this early exposure exacerbates antiandrogen-induced penis abnormalities.

Background:Congenital abnormalities vary in presentation, yet studies using model organisms tend to focus on occurrence rather than severity of the defect. Scoring severity of abnormalities in model systems allows explicit hypothesis testing during basic, translational, and reverse translational studies. We developed and validated a protocol to quantify severity of male urogenital feminization (hypospadias) in the mouse model. Hypospadias is one of the most common birth defects in the world.Methods:To induce genital feminization, pregnant mice were exposed to different concentrations of the antiandrogen vinclozolin. Genitalia were photographed at gestational age 18.5. A dichotomous scoring system to evaluate genital feminization was developed, and validated against histological measurements of urethral length. A training protocol was developed for novice scorers, and criteria were defined to evaluate precision and accuracy of scores.Results:Vinclozolin induced variation in hypospadias severity. Severity scores were tightly correlated with histologically determined urethral length and both techniques showed similar dose–response relationships. Novice observers were trained to precisely and accurately score hypospadias severity.Conclusion:This standardized scoring system advances the mouse as a model to study urogenital development, and will facilitate research on the mechanisms driving genital feminization in males, and aid translational hypospadias research.

Tradeoffs between time to and size at metamorphosis occur in many organisms with complex life histories. The ability to accelerate metamorphosis can increase survival to the next life stage, but the resulting smaller size at metamorphosis is often associated with lower post‐metamorphic survival or reduced fecundity of adults. Reduced fecundity is thought to be because of reduced energy reserves, longer time to maturity, or reduced capacity to carry eggs or compete for mates. This pattern could also be explained by a shift in allocation to somatic growth that further retards the growth or development of reproductive tissues. The main goal of this study was to determine if the relationship between growth and development of somatic and gonadal tissues depends on environmental conditions. We address this question through two experiments in which we quantify the development and growth of the body and gonads of Xenopus laevis reared in different resource environments. First, tadpoles were reared communally and development and growth were evaluated over time. Restricted food reduced somatic and gonadal growth rate, but did not affect the developmental rate of either tissue type. Second, tadpoles were reared individually and evaluated at metamorphosis. Restricted food reduced somatic development and growth, but only influenced size, and not developmental stage of testes at metamorphosis. This work demonstrates that environmental conditions influence tradeoffs between growth and development of somatic and gonadal tissues, apparently in a sex‐specific manner. These tradeoffs may contribute to phenotypic correlations between small size and reduced fitness J. Exp. Zool. 307A:637–646, 2007. © 2007 Wiley‐Liss, Inc.