Seminal transforming growth factor-β in normal and infertile men

Transforming growth factor-β (TGFβ) 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) TGFβ in seminal plasma from normal subjects (n J 23) and infertile (n J 40) patients, by using a TGFβ specific immunoenzymological assay, and a bioassay (CCL64 cell line growth inhibition) detecting any form of TGFβ. Free TGFβ1 was present in normal subjects at a concentration (1.82 K 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 TGFβ1 was present in normal seminal plasma at a high concentration (92.4 K 29.2 ng/ml). In subjects with pathologies of both testis and genital apparatus, or with epididymal occlusion, mean latent TGFβ1 concentrations were normal, whereas transferrin concentrations were lower. The concentrations found in the epididymal occlusion group indicate that TGFβ1 is, for a large part, secreted by the genital tract. In the testicular pathology group, TGFβ1 concentrations were 130.7 K 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 TGFβ1 in seminal plasma is not of testicular origin. The TGFβ bioassay ensured that immunologically detected TGFβ 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 TGFβ might be present. Together, the present data show that very large amounts of TGFβ are present in human seminal plasma. The TGFβ ligand assay in the seminal plasma appears to indicate no differences between normal and infertile subjects.