title: Partial Müllerian Duct Retention in Smad4 Conditional Mutant Male Mice.
abstract: Müllerian duct regression is a complex process which involves the AMH signalling pathway. We have previously demonstrated that besides AMH and its specific type II receptor (AMHRII), BMPR-IA and Smad5 are two essential factors implicated in this mechanism. Mothers against decapentaplegic homolog 4 (Smad4) is a transcription factor and the common Smad (co-Smad) involved in transforming growth factor beta (TGF-β) signalling pathway superfamily. Since Smad4 null mutants die early during gastrulation, we have inactivated Smad4 in the Müllerian duct mesenchyme. Specific inactivation of Smad4 in the urogenital ridge leads to the partial persistence of the Müllerian duct in adult male mice. Careful examination of the urogenital tract reveals that the Müllerian duct retention is randomly distributed either on one side or both sides. Histological analysis shows a uterus-like structure, which is confirmed by the expression of estrogen receptor α. As previously described in a β-catenin conditional mutant mouse model, β-catenin contributes to Müllerian duct regression. In our mutant male embryos, it appears that β-catenin expression is locally reduced along the urogenital ridge as compared to control mice. Moreover, the expression pattern is similar to those observed in control female mice. This study shows that reduced Smad4 expression disrupts the Wnt/β-catenin signalling leading to the partial persistence of Müllerian duct.
authors.affiliation: 1. Institut National de la Santé et de la Recherche Médicale, Institut de Recherche en Santé, Environnement et Travail, UMR1085, Université de Rennes 1, Rennes, France;; 2. Institut National de la Santé et de la Recherche Médicale, U782, Clamart, France.
authors.forename: Fabrice G
authors.initials: FG
authors.lastname: Petit
authors.affiliation: 3. Faculty of Health Sciences, University of Macau, Macau SAR, China.
authors.forename: Chuxia
authors.initials: C
authors.lastname: Deng
authors.affiliation: 1. Institut National de la Santé et de la Recherche Médicale, Institut de Recherche en Santé, Environnement et Travail, UMR1085, Université de Rennes 1, Rennes, France;; 2. Institut National de la Santé et de la Recherche Médicale, U782, Clamart, France.
authors.forename: Soazik P
authors.initials: SP
authors.lastname: Jamin
mesh_terms: D000818:Animals; D052005:Bone Morphogenetic Protein Receptors, Type I / Q000235:genetics / Q000378:metabolism; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005091:Exons / Q000235:genetics; D005260:Female; D005455:Fluorescent Antibody Technique; D018507:Gene Expression Regulation, Developmental / Q000235:genetics / Q000502:physiology; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D008817:Mice, Mutant Strains; D009095:Mullerian Ducts / Q000378:metabolism* / Q000473:pathology*; D015398:Signal Transduction / Q000235:genetics / Q000502:physiology; D051901:Smad4 Protein / Q000235:genetics / Q000378:metabolism*; D051902:Smad5 Protein / Q000235:genetics / Q000378:metabolism; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism
chemical_list: D047628:Estrogen Receptor alpha; C497797:SMAD5 protein, human; D051901:Smad4 Protein; D051902:Smad5 Protein; D051176:beta Catenin; C498212:Bmpr1a protein, mouse; D052005:Bone Morphogenetic Protein Receptors, Type I
keywords: Müllerian duct; Smad4; conditional knockout; β-catenin.