P-041 Impact of ionizing radiation on human spermatozoa integrity

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Abstract Study question Do ionizing radiations affect human sperm integrity? If so, at what dose? Summary answer In vitro exposure of human ejaculated spermatozoa significantly reduces vitality, motility, and chromatin integrity without causing DNA fragmentation, telomeric damage, or altering capacitation ability. What is known already Exposure to ionizing radiation (IR) is a public health concern. However, its impact on human spermatozoa remains poorly described, particularly regarding nuclear damage. Our objective is to assess the impact of IR on functional parameters, as well as on nuclear quality. To achieve this, we expose human spermatozoa in vitro to increase doses of IR, reflecting various diagnostic and therapeutic medical scenarios. This study will help elucidate the mechanisms by which IR affects male fertility and, consequently, optimize fertility preservation strategies. Study design, size, duration We exposed human spermatozoa in vitro to increase IR doses mimicking epididymis irradiation during medical procedure: diagnostic imaging (scanner CT: 14–70 mGy) and radioiodine therapy (140 mGy). Sperm vitality, motility, DNA fragmentation, chromatin decondensation, telomere length (STL), nuclear morphometry, oxidative stress and capacitation markers post-IR were compared to their non-irradiated controls for each patient to address inter-individual variability. Participants/materials, setting, methods We used surplus semen from patient having consented to research (Germethèque Biobank). Gamma radiation conditions mimicking CT doses of 14 (n = 35), 70 (n = 39), and 140 mGy (n = 73) were experimentally calibrated. Sperm parameters (WHO 2021 guidelines), DNA fragmentation (TUNEL/SCD assays), chromatin decondensation (Chromomycin A3), STL (qPCR), nuclear morphometry (3D bioimage analysis), oxidation (Oxiselect/MDA kits) and capacitation markers -velocity (SCA© CASA), [AMPc] (ELISA), phosphotyrosine profile (Western blot) and acrosome integrity (PSA-FITC)- were evaluated. Main results and the role of chance The three dose groups showed no significant differences in initial sperm parameters or bio-clinical criteria, confirming the absence of biases. We observed a significant decrease in sperm vitality across all three radiation doses compared to the non-irradiated control condition (-3.4% for 14 mGy, -4.2% for 70 mGy, and -5.6% for 140 mGy; p < 0.001). Progressive motility was reduced at 140 mGy (37.0 ± 2.3% versus (vs.) 33.1 ± 2.0% after IR exposure; -3.9%, p < 0.001). IR induced chromatin decondensation at 70 mGy (23.6 ± 1.9% vs. 26.0 ± 1.8%, +2.3%, p < 0.05) and 140 mGy (23.5 ± 1.3% vs. 26.1 ± 1.5%, +2.5%, p < 0.01), with greater decondensation observed in samples with pre-existing sperm parameter alterations (+3.5%, p < 0.05). No significant changes were detected in DNA fragmentation levels (TUNEL or SCD assays) or sperm telomere length (STL). Exposure to 140 mGy did not significantly alter oxidative levels in seminal fluid or sperm cells, nor did it affect capacitation markers, although motility alterations were identified using SCA®. Finally, no significant global impact on 3D nuclear morphometric parameters has been observed to date. Limitations, reasons for caution This model provides an opportunity to analyze IR-induced alterations without patients/pathology’s interference. Differences in dose rate, exposure duration, and the spermatozoa environment (seminal instead of epididymal fluid) represented limitations. In vivo studies are essential to fully understand the impacts of IR on the regulation pathways of spermatogenesis and sperm maturation. Wider implications of the findings We show for the first time the impact of IR on human sperm quality using three radiations doses used for clinical diagnosis or treatment. Significant but minor effects on conventional parameters and chromatin decondensation were observed. Ongoing work includes epigenomic alterations from sperm cells and seminal fluid to further investigate. Trial registration number Yes

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