Transforming growth factor‐beta 2 heterozygous mutant mice exhibit Cowper's gland hyperplasia and cystic dilations of the gland ducts (Cowper's syringoceles)

Analyses of mutant mice with a deletion for the transforming growth factor beta 2 (Tgfbeta2) gene revealed cysts in the perineal/scrotal region of male mice. We present evidence from in situ, light and electron microscopy that the cysts observed in Tgfbeta2+/- heterozygous mice males derive from Cowper's gland tissue. The Cowper's glands of Tgfbeta2+/- heterozygous mutant mice display all steps of glandular hyperplasia and cystic dilation. TGF-beta isoforms and TGF-beta receptor (TbetaR-II) were localized immunocytochemically in sections of Cowper's glands. TGF-beta2 and TGF-beta3 were located predominantly in myoepithelial cells of the Cowper's gland whereas the TbetaRII was found in the plasma membrane of the acinar cells. TUNEL-assays revealed that apoptotic cell death is significantly reduced in Cowper's glands of TgfbetaB2+/- heterozygous mutant mice. The fact that Tgfbeta2+/- heterozygous mutant mice exhibit hyperplasia of Cowper's gland epithelium and Cowper's gland cysts suggests a disturbance of epithelial-stromal interaction most likely due to reduced TGF-beta2 level, accompanied by a significant decrease in apoptosis.