Meeting Abstract
In recent decades, there has been a rise of endocrine-related diseases and disorders, including an increased incidence of genital malformations, low semen quality, adverse pregnancy outcomes, neurobehavioral disruption, endocrine-related cancers, earlier onset of breast development, obesity, and type 2 diabetes. An example of increased genital malformations is seen with congenital penile anomaly (CPA) frequency, which has increased to a rate of 1 in 125, or 0.83%, of male newborns. The most commonly reported CPA is hypospadias, which accounts for 68.3% of CPAs. Hypospadias is characterized by an atypical urethral opening along the penile shaft, within the scrotum, or in the perineum. Chordee, or penile curvature, accounts for 8.6% of CPAs, while hypospadias plus chordee make up 5% of CPAs. Chordee without hypospadias is a congenital anomaly that usually results in a ventrally tethered penis and normally positioned urethral opening. We found that male mouse embryos exposed to the endocrine disruptor vinclozolin develop external genital defects that mimic human congenital penile anomalies. Female mouse embryos exposed to vinclozolin also develop external genital defects. We have investigated the molecular mediators vinclozolin-induced genital defects and find that these malformations result from disruption of the activity of genes that normally pattern the genital tubercle.
