Impact of Chemotherapy on Sperm Functional Characteristics in Patients With Testicular Germ Cell Tumours

Testicular germ cell tumours (TGCT) are the most common malignancies among young men and represent a major threat to reproductive health. Both the disease itself and oncological treatments, particularly chemotherapy, can compromise spermatogenesis and semen quality.

To evaluate sperm qualitative parameters in patients diagnosed with TGCT who underwent orchiectomy, assessed before chemotherapy and at 3 and 6 months post-treatment, to monitor their reproductive health with respect to the type of oncological therapy.

Semen samples from seminoma and non-seminoma patients were analysed before and after chemotherapy. Standard spermiogram, flow cytometry (viability, apoptosis, DNA damage, acrosome integrity), sperm motility clustering, and western blot detection of histone modifications (H4K12ac, H3K9ac, H3K36me3) were used to assess chemotherapy-related sperm alterations.

Before chemotherapy, non-seminoma patients showed higher sperm count and volume than seminoma patients. Chemotherapy, particularly BEP, caused severe impairment, with azoospermia and necrozoospermia observed. Normozoospermia declined rapidly in non-seminoma patients, while seminoma showed milder effects. DNA fragmentation, apoptosis, and acrosome integrity remained unchanged. Notably, histone H4K12ac abundance correlated positively with motility, sperm count, morphology, and DNA integrity.

Non-seminoma patients had initially better semen quality, which declined rapidly during chemotherapy. Our findings highlight the need for extended sperm analysis in cancer and pathological conditions. Importantly, sperm quality correlated positively with histone H4K12ac abundance, underscoring its clinical relevance in chromatin regulation and paternal contributions to embryonic development.

Sperm quality in TGCT patients showed marked variability. Non-seminoma diagnosis appeared less detrimental than seminoma, yet BEP chemotherapy severely impaired sperm parameters, especially in non-seminoma cases. These results highlight the importance of individualized post-chemotherapy monitoring using standard semen analysis, cytometry-based qualitative assessments, and epigenetic profiling of histone modifications to optimize fertility preservation and guide optimal treatment strategies by andrologists.