Molecular Actions Underlying Wolffian Duct Regression in Sexual Differentiation of Murine Reproductive Tracts

Abstract

Sexually dimorphic establishment of the reproductive tract system requires sex-specific regression of the Wolffian duct and Müllerian duct in the mesonephros. In an XX embryo, the Wolffian duct regresses under the control of the mesenchymal transcription factor COUP-TFII. To understand cellular and molecular actions underlying Wolffian duct regression, we performed transcriptomic analyses of XX mesonephroi with or without Coup-tfII and genome-wide analysis of COUP-TFII chromatin occupancy in XX mesonephroi. The integrative analysis of COUP-TFII genome-wide binding and transcriptomic analysis revealed the suppression of muscle differentiation and extracellular matrix genes by COUP-TFII and identified a group of potential transcriptional partners of COUP-TFII in the mesenchyme that potentially facilitate Wolffian duct regression. These findings provide insights into the molecular action of COUP-TFII in the Wolffian duct mesenchyme and identify a list of biologically relevant candidate genes and pathways for future functional analyses in sexual differentiation of reproductive tracts.