A Tale of Two Tracts: History, Current Advances, and Future Directions of Research on Sexual Differentiation of Reproductive Tracts†

Alfred Jost's work in the 1940s laid the foundation of the current paradigm of sexual differentiation of reproductive tracts, which contends that testicular hormones drive the male patterning of reproductive tract system whereas the female phenotype arises by default. Once established, the sex-specific reproductive tracts undergo morphogenesis, giving rise to anatomically and functionally distinct tubular organs along the rostral-caudal axis. Impairment of sexual differentiation of reproductive tracts by genetic alteration and environmental exposure are the main causes of disorders of sex development, and infertility at adulthood. This review covers past and present work on sexual differentiation and morphogenesis of reproductive tracts, associated human disorders, and emerging technologies that have made impacts or could radically expand our knowledge in this field.