transforming-growth-factor-beta and Genital-Diseases--Male

Topics: Arthrodesis; Bone Morphogenetic Proteins; Ejaculation; Gelatin Sponge, Absorbable; Genital Diseases, Male; Humans; Lumbar Vertebrae; Male; Postoperative Complications; Recombinant Proteins; Spondylolisthesis; Transforming Growth Factor beta; Treatment Outcome; United States; United States Food and Drug Administration

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.

Topics: Animals; Apoptosis; Bulbourethral Glands; Cysts; Genital Diseases, Male; Heterozygote; Hyperplasia; Immunohistochemistry; In Situ Nick-End Labeling; Male; Mice; Mice, Mutant Strains; Mice, Transgenic; Microscopy, Electron; Receptors, Transforming Growth Factor beta; Transforming Growth Factor beta; Transforming Growth Factor beta2

Transforming growth factor-beta (TGFbeta) is a cytokine with autocrine and paracrine action in the testis and potent immunoregulatory and anti-inflammatory activities. In the present study, we examined the concentration of latent (acid-activatable) and free (active) TGFbeta in seminal plasma from normal subjects (n = 23) and infertile (n = 40) patients, by using a TGFbeta specific immunoenzymological assay, and a bioassay (CCL64 cell line growth inhibition) detecting any form of TGFbeta. Free TGFbeta1 was present in normal subjects at a concentration (1.82 +/- 1.06 ng/ml) close to that known to give maximal stimulation in vitro. In pathological groups, the mean concentrations were not significantly different from the normal ones. Latent TGFbeta1 was present in normal seminal plasma at a high concentration (92.4 +/- 29.2 ng/ml). In subjects with pathologies of both testis and genital apparatus, or with epididymal occlusion, mean latent TGFbeta1 concentrations were normal, whereas transferrin concentrations were lower. The concentrations found in the epididymal occlusion group indicate that TGFbeta1 is, for a large part, secreted by the genital tract. In the testicular pathology group, TGFbeta1 concentrations were 130.7 +/- 61.2 ng/ml, a mean not statistically different from normal, although higher. No differences were found between patients with high and normal blood plasma follicle stimulating hormone, and this is consistent with the notion that most TGFbeta1 in seminal plasma is not of testicular origin. The TGFbeta bioassay ensured that immunologically detected TGFbeta was present in a bioactive or bioactivatable form. Furthermore, the values found in normal and pathological seminal plasmas were usually higher than those detected by the immunoassay, suggesting that other forms of TGFbeta might be present. Together, the present data show that very large amounts of TGFbeta are present in human seminal plasma. The TGFbeta ligand assay in the seminal plasma appears to indicate no differences between normal and infertile subjects.

Topics: Animals; Cell Division; Cell Line; Epididymis; Epithelial Cells; Genital Diseases, Male; Humans; Immunoenzyme Techniques; Infertility, Male; Lung; Male; Mink; Semen; Testicular Diseases; Transferrin; Transforming Growth Factor beta