Meeting Abstract
Hypospadias has increased 400% in the past 40 years, making it the second most common birth defect in the USA. Hypospadias occurs when altered androgen signaling disrupts penile development and results in mis-localization of the urethra ventrally along the shaft of the penis. Variation in severity of hypospadias is likely caused by a number of molecular mechanisms, which have not been adequately evaluated. In fact, evaluating hypospadias as a binary trait (presence or absence) could increase noise in the data and reduce our ability to investigate the developmental genetics driving variation in hypospadias severity. We developed a standardized visual scoring system for the mouse model to evaluate hypospadias severity with hopes to better compare results across studies, chemicals, and doses. Pregnant CD1 mice (n=3) were gavaged with corn oil control, 100, 125 or 150 mg/kg of vinclozolin during the genitalia masculinization window (embryonic days (E) 13.5-16.5). Genitalia of E18.5 pups were fixed, photographed, encrypted, and randomly assorted. Three researchers, blind to treatment, scored hypospadias presence (proportion of pups with hypospadias) and severity (scale of 1-3 indicating whether the urethral meatus opens in the distal third (1), mid-shaft (2), or proximal third of the penis (3)). Other penile abnormalities were also recorded. Each researcher scored twice so inter- and intra- score validity could be determined and incorporated into the scoring system. Histological evaluation of penile length and urethral opening was used to validate our scoring system. Indeed, our visual scoring system was representative of the histological data. A standardized scoring system will improve our ability to compare variation in hypospadias severity across studies, within and among laboratories.
