| First Author | Tanwar PS | Year | 2010 |
| Journal | Proc Natl Acad Sci U S A | Volume | 107 |
| Issue | 37 | Pages | 16142-7 |
| PubMed ID | 20805501 | Mgi Jnum | J:164361 |
| Mgi Id | MGI:4833718 | Doi | 10.1073/pnas.1011606107 |
| Citation | Tanwar PS, et al. (2010) Focal Mullerian duct retention in male mice with constitutively activated beta-catenin expression in the Mullerian duct mesenchyme. Proc Natl Acad Sci U S A 107(37):16142-7 |
| abstractText | Mullerian-inhibiting substance (MIS), which is produced by fetal Sertoli cells shortly after commitment of the bipotential gonads to testicular differentiation, causes Mullerian duct (MD) regression. In the fetal female gonads, MIS is not expressed and the MDs will differentiate into the internal female reproductive tract. We have investigated whether dysregulated beta-catenin activity affects MD regression by expressing a constitutively activated nuclear form of beta-catenin in the MD mesenchyme. We show that constitutively activated (CA) beta-catenin causes focal retention of MD tissue in the epididymides and vasa deferentia. In adult mutant mice, the retained MD tissues express alpha-smooth muscle actin and desmin, which are markers for uterine differentiation. MD retention inhibited the folding complexity of the developing epididymides and usually led to obstructive azoospermia by spermatoceles. The MDs of urogenital ridges from mutant female embryos showed less regression with added MIS in organ culture compared with control MDs when analyzed by whole mount in situ hybridization for Wnt7a as a marker for the MD epithelium. CA beta-catenin did not appear to affect expression of either MIS in the embryonic testes or its type II receptor (AMHR2) in the MD mesenchyme nor did it inhibit pSmad1/5/8 nuclear accumulation, suggesting that dysregulated beta-catenin must inhibit MD regression independently of MIS signaling. These studies suggest that dysregulated Wnt/beta-catenin signaling in the MD mesenchyme might also be a contributing factor in persistent Mullerian duct syndrome, a form of male pseudohermaphroditism, and development of spermatoceles. |
