Supplementary Material for: Molecular Actions Underlying Wolffian Duct Regression in Sexual Differentiation of Murine Reproductive Tracts

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 <i>Coup-tfII</i> 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.

生殖管道系统的性别二态性建立，需要中肾内沃尔夫管（Wolffian duct）与米勒管（Müllerian duct）发生性别特异性退化。在XX型胚胎中，沃尔夫管在间质转录因子COUP-TFII的调控下发生退化。为阐明沃尔夫管退化背后的细胞与分子机制，本研究对存在或缺失Coup-tfII的XX型中肾组织开展了转录组分析，并对XX型中肾组织进行了COUP-TFII全基因组染色质结合位点分析。通过整合COUP-TFII全基因组结合数据与转录组分析结果，本研究揭示了COUP-TFII对肌肉分化相关基因及细胞外基质基因的抑制作用，并鉴定出间质中一组可潜在促进沃尔夫管退化的COUP-TFII潜在转录调控伙伴。本研究结果为解析COUP-TFII在沃尔夫管间质中的分子调控机制提供了新见解，同时筛选出一系列与生殖管道性别分化相关的候选基因及调控通路，为后续相关功能研究提供了具有生物学意义的研究靶点。