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Génotoxicité des chimiothérapies et radiothérapies: Quelles sont les conséquences pour le spermatozoïde humain?

Genotoxicity of chemotherapy and radiotherapy: What are consequences for human spermatozoa?

Andrologie volume 12, pages 284–294 (2002)Cite this article

Resume

Le pronostic des cancers de l’homme jeune en âge de procréer s’est considérablement amélioré ces dernières décades grâce aux progrès thérapeutiques. Les chimiothérapies et radiothérapies ont des effets bien connus sur la spermatogenèse. Au dela de l’atteinte quantative et qualitative de la spermatogenèse, des études réalisées chez l’animal ont pu mettre en évidence des atteintes nucléaires (aneuploïdie, présence d’adduits, fragmentation de l’ADN…) et parfois des atteintes au niveau des générations F1 et F2. Chez l’homme, l’étude des chromosomes des spermatozoïdes après radiothérapie a mis en évidence une augmentation de la fréquence des anomalies chromosomiques. Concernant la chimiothérapie, les premières études utilisaient la technique de fécondation hétérospécifique pour mettre en évidence les anomalies chromosomiques du spermatozoïde. Plus récemment, la technique d’hybridation de sondes chromosomiques fluorescentes (FISH) permet d’étudier plusieurs chromosomes sur un grand nombre de spermatozoides. Les résultats des différentes études portant sur des effectifs réduits sont variables en fonction du protocole thérapeutique administré et de la durée séparant le prélèvement de la fin du traitement. Nous avons étudié 5 patients ayant fait un prélèvement de sperme 6 à 17 mois après le protocole de chimiothérapie BEP (Bléomycin, Etoposide, Cisplatin). Nous avons mis en évidence une augmentation du taux de spermatozoïdes présentant une aneuploïdie et une diploïdie. Les résultats de notre étude et de celles du groupe de R. Martin [45, 47] évoquent la possibilité d’un effet transitoire de la chimiothérapie sur les chromosomes gamétiques. Dans le cadre de la maladie de Hodgkin d’autres études ont mis en évidence l’aspect transitoire de l’effet sur l’aneuploïdie. Au dela de l’atteinte chromosomique, l’action délétère des traitements pourrait avoir pour cible l’ADN du spermatozoïde. Ainsi des études sur des effectifs importants, utilisant d’autres métodes d’analyse nous parraissent nécessaires. Dans l’attente, il paraît souhaitable de toujours conseiller l’autoconservation de sperme avant les traitements et d’adopter une grande prudence lors du conseil apporté aux patients désirant une grossesse, précocément, après la fin des traitements.

Abstract

The prognosis of cancer in young men of childbearing potential has been considerably improved over recent decades as a result of therapeutic progress. Chemotherapy and radiotherapy have well known effects on spermatogenesis. Apart from quantitative and qualitative impairment of spermatogenesis, animal studies have also demonstrated nuclear lesions (aneuploidy, presence of adducts, DNA fragmentation, etc.) and sometimes lesions affecting the F1 and F2 generations. Chromosomal studies of human spermatozoa after radiotherapy have demonstrated an increased frequency of chromosomal anomalies. The first studies concerning the effects of chemotherapy used the heterospecific fertilization technique to demonstrate spermatozoal chromosomal anomalies. More recently, thefluorescence in situ hybridization (FISH) technique has been used to study several chromosomes on a large number of spermatozoa. The results of various studies based on small sample sizes vary as a function of the therapeutic protocol administered and the time of sperm collection in relation to the end of treatment. We studied 5 patients who provided a semen sample 6 to 17 months after completing the BOE chemotherapy protocol (Bleomycin, Etoposide, Cisplatin). We demonstrated an increased rate of aneuploid and diploid spermatozoa. The results of our study and those reported by R. Martin et al. [45, 47] suggest the possibility of a transient effect of chemotherapy on gamete chromosomes. Other studies, conducted in the context of Hodgkin’s disease, have demonstrated the transient nature of the aneuploidy effect. Apart from the harmful action on chromosomes, treatments could also damage spermatozoal DNA. Studies conducted on larger sample sizes and using other methods of analysis therefore appear to be essential. In the meantime, it appears preferable to systematically propose semen cryopreservation before treatment and to provide very cautious advice to patients desiring a pregnancy soon after completion of treatment.

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  1. Groupe de Recherche en fertilité Humaine et CECOS Midi-Pyrénées, Hôpital La Grave, TSA 60033, 31059, Toulouse Cedex 9, France

    Louis Bujan

  2. Service de Génétique médicale, CHU Purpan, Toulouse

    Philippe De Mas

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  1. Louis Bujan
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  2. Philippe De Mas
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Bujan, L., De Mas, P. Génotoxicité des chimiothérapies et radiothérapies: Quelles sont les conséquences pour le spermatozoïde humain?. Androl. 12, 284–294 (2002). https://doi.org/10.1007/BF03035141

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Basic and Clinical Andrology

ISSN: 2051-4190