The molecular anatomy of human genital development

Human genital development shows marked differences compared to other species, but remains one of the least researched developmental processes. Variations in genital development, such as hypospadias are remarkably common. A clear genetic condition is sometimes responsible, but often the underlying cause is unknown. Most variations in genital development result from altered developmental processes between 8-16 weeks post conception. These are anatomically complex and poorly understood. Current surgical interventions, if undertaken, are challenging. Psychological consequences need to be considered (e.g. body-image, urological and sexual function), but greater nuanced support is needed. To address these challenges we propose a multimodal, integrated approach using transcriptomics, bio-imaging, model systems and clinical insight to: 1) define molecular mechanisms of penile urethral closure, penis growth and novel causes of hypospadias; 2) define the molecular basis of clitoral and urogenital sinus remodelling, clitoral/vaginal innervation, and consequences for complex uro-gynaecological conditions; 3) investigate sex differences in fetal adipose tissue development, which we feel are inherently linked to genital development; 4) develop our work on lived experiences, support and positive educational impact of our findings. We anticipate this project will lead to novel management options, and will have wider implications for understanding sex development/function.