Hypospadias is a congenital abnormality in males, characterised by the abnormal termination of the urethral opening on the penis. Hypospadias is one of the most common disorders of sexual development (DSD), occurring in 1 in every 125 live male births in Australia and the U.S.A. Alarmingly the incidence of hypospadias has doubled in recent decades. This increase has been largely attributed to environmental endocrine disruptors (EEDs), which disrupt the delicate balance of hormonal signals required for normal penis development. Several human epidemiological studies have linked vegetarian and vegan diets to a 3-4 fold increase risk of hypospadias. These diets are typically high in plant based oestrogenic compounds (phytoestrogens), specifically genistein. However, a direct link between genistein exposures and hypospadias has not been defined, and is a major gap in our current knowledge of maternal diet-linked congenital abnormalities.
To address this question we have used our established high throughput ex vivo organotypic culturing system alongside micro-CT scanning and RNA seq experiments to conclusive demonstrate that the phytoestrogen genistein directly induces hypospadias and other penile abnormalities. Additionally, through our transcriptome analysis we have uncovered a previously unknown association with phytoestrogens and erectile dysfunction, a condition which is suspected to have increased, similar to hypospadias, over the past few decades. These findings provide a significant new insight into the risks associated with maternal ingestion of phytoestrogens over the window of penis development.
This work was supported in part by the NIH: R01 DK096263 to Pask.