Authors
Min Chen, Xin Qi, Shanshan Qin, Jia Kang, Changhuo Cen, Miao Guo, Yang Gao, Mengyue Wang, Jiayi Li, Xiuhong Cui, Yanbo Wang, Lan Zhu, Fei Gao
Published in
Cell proliferation. Pages e70264. Jul 14, 2026. Epub Jul 14, 2026.
Abstract
In mammals, Müllerian ducts (MDs) are the precursors of the female reproductive tract which regress in males during embryonic development. Failure of MD regression results in persistent Müllerian duct syndrome (PMDS) in humans. Although several factors essential for MD regression have been identified, the underlying regulatory network remains incompletely understood. In this study, we found that the Wilms tumour gene (Wt1) was highly expressed in the MD mesenchyme of male mice. Mesenchyme-specific inactivation of Wt1 resulted in MD retention and male infertility. The expression of Amh in the testes and its receptor Amhr2 in the MD mesenchyme remained unchanged in Wt1-/flox; Amhr2-cre male mice. Instead, the expression of Wnt inhibitory factor 1 (Wif1) and Osterix (Osx) was significantly reduced, accompanied by nuclear accumulation of β-catenin in the MD mesenchyme of Wt1-deficient mice. Further studies revealed that Wif1 and Osx were direct transcriptional targets of WT1. These findings identify Wt1 as a previously unrecognized mesenchymal regulator of MD regression by inducing Wif1 and Osx expression and provide new insights into the regulatory mechanisms underlying MD regression as well as the aetiology of reproductive tract disorders associated with WT1 mutations.
PMID:
42444324
Bibliographic data and abstract were imported from PubMed on 14 Jul 2026.
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