Acute lymphoblastic leukaemia in rats induces pathomorphological changes in germ cells

Concern about the reproductive potential of long-term survivors of acute lymphoblastic leukaemia (ALL) prompted an investigation into the impact of the disease on spermatogenic cells. Using rats as a model, histological, immunocytochemical and electron microscopic analysis was applied to investigate changes in the seminiferous epithelium. In rats transplanted with leukaemic cells at early puberty, degenerate primary spermatocytes and spermatids were prevalent within stage VIII tubules. Electron microscopically, step 8 spermatids showed acrosomal abnormalities and nuclear contour distortion. In the distorted step 9 spermatids, the microtubules of the manchette were abnormally oriented or deficient. Antitubulin antibody staining was reduced in elongating spermatids in the group transplanted with leukaemic cells at early puberty but was not observed in the older leukaemic group. Step 13 spermatids showed extracted chromatin and degenerate step 19 spermatids were occasionally found. Similar but less severe changes were seen in the group of rats transplanted with leukaemic cells at late puberty. We conclude that germinal cell damage induced by ALL is dependent on the developmental maturity of the seminiferous epithelium. The present findings are of particular importance when interpreting the impact of anticancer chemotherapeutics on germinal cells in patients with ALL.