The proliferation of spermatogonia in normal and pathological human seminiferous epithelium: an immunohistochemical study using monoclonal antibodies against Ki-67 protein and proliferating cell nuclear antigen

The quantitative distribution pattern of Ki-67 protein and proliferatingcell nuclear antigen (PCNA) immunoreactivity was studied in human testisbiopsies. In normal seminiferous epithelium Ki-67 is expressed in nuclei ofspermatogonia, while PCNA additionally occurs in nuclei of primaryspermatocytes. The staining pattern of spermatogonia is as follows(Ki-67-positive/PCNA-positive): 26.6 +/- 12.4%/46.3 +/- 9.5%. Nostage-dependent differences were found. Biopsies with mixed atrophy (score< or =7) showed a significant (P < 0.05) decrease of immunopositivespermatogonia to 19.9 +/- 3.0%/31.4 +/- 5.7% (score 1) with minimalvariation between different samples (score 7 to 1). Associated with definedhistological defects such as hypospermatogenesis (hyp), spermatogenicarrest at the level of spermatids (sda), spermatocytes (sca) orspermatogonia (sga), however, there was a significant (P < 0.05)decrease of Ki-67 staining in tubules showing hyp (28.6 +/- 8.8%), sda(25.6 +/- 9.3%), sca (23.7 +/- 9.3%) and sga (16.2 +/- 6.0%) and of PCNAstaining in sca (32.2 +/- 11.8%) and sga (20.0 +/- 9.5%), respectively. Thedecrease of immunoreactive spermatogonia did not correspond to elevation offollicle stimulating hormone (FSH). These data demonstrate that the lowspermatogenic efficiency in infertile men is not only due to postmeioticevents, but also to a decrease in the meiotic activity of spermatogonia,and is not related to serum FSH.