Abstract
The female reproductive tract develops from its embryonic precursor, the Müllerian duct. In close proximity to the Müllerian duct lies the precursor for the male reproductive tract, the Wolffian duct, which is eliminated in the female embryo during sexual differentiation. We discovered that a component of the Wolffian duct, its mesenchyme, is not eliminated after sexual differentiation. Instead, the Wolffian duct mesenchyme underwent changes in transcriptome and chromatin accessibility from male tract to female tract identity, and became a unique mesenchymal population in the female reproductive tract with localization and transcriptome distinct from the mesenchyme derived from the Müllerian duct. Partial ablation of the Wolffian duct mesenchyme stunted the growth of the fetal female reproductive tract in ex vivo organ culture. These findings reveal a new fetal origin of mesenchymal tissues for female reproductive tract formation and reshape our understanding of sexual differentiation of reproductive tracts.