Sperm Telomere Interactions Are Impaired in Testicular Cancer Before and After Adjuvant Therapy

No study has yet explored telomere length or interaction in sperm nuclei of testicular cancer (TC) patients exposed to chemotherapy or radiotherapy. However, sperm telomere dynamics have emerged as a potential marker in male infertility.

We aimed to investigate in a pilot and exploratory study whether TC and its adjuvant treatments alter sperm telomeres and DNA integrity during a 2-year follow-up after treatment.

This ancillary study is part of the multicentric prospective and longitudinal French GAMATOX study. Twenty-nine TC patients treated with orchiectomy and either adjuvant chemotherapy (n = 14) or radiotherapy (n = 15) were included, alongside ten fertile donors. Semen samples were collected before orchiectomy and adjuvant therapy, and at 3, 6, 12, and 24 months after treatment. Sperm telomere length (STL) and telomere interactions were assessed by quantitative fluorescent in situ hybridisation (FISH). Sperm DNA fragmentation (SDF) was measured using the TUNEL assay, aneuploidy by FISH, and chromatin condensation defects by aniline blue staining.

Before adjuvant therapy, patients presented a higher number of sperm telomere signals compared with controls (p = 0.004), persisting 2 years after treatment (p = 0.001). STL was not affected by tumour histology. Extremely short telomeres and the highest number of telomere signals per nucleus were more frequently observed after chemotherapy. SDF and chromatin condensation defects were transient and paralleled the recovery of conventional semen parameters, regardless of treatment type. A moderate increase in sperm aneuploidy was observed 6 months after chemotherapy (p = 0.03).

TC patients presented impaired sperm telomere interactions before and after adjuvant therapy, as reflected by a persistently elevated number of telomere signals per nucleus, and a higher prevalence of extremely short sperm telomeres, especially after chemotherapy. While relative STL remained comparable to controls, these findings raise questions about the impact of telomere architecture on germ cell tumour biology and post-treatment fertility.