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Conservation de tissu testiculaire et maturation in vitro de la lignée germinale pour préservation du potentiel de reproduction avant traitement anticancéreux chez le garçon pré-pubère

Conservation of testicular tissues and in vitro maturation of male germ cells for preservation of reproductive potential before cancer treatment in prepubertal boy

Résumé

La cryoconservation des spermatozoïdes avant traitement chimio-radiothérapique stérilisant permet de préserver des possibilités de reproduction chez l’homme adulte. En l’absence de spermatozoïdes matures, des mesures de préservation du potentiel de reproduction n’ont pas pu, jusqu’ici, être envisagées chez l’enfant, alors même que le taux de guérison de certaines pathologies malignes est important à cet âge. Cette revue se propose de faire le point sur les avancées récentes qui ouvrent des perspectives de conservation et de maturationin vitro de cellules germinales masculines immatures qui pourraient être prélevées chez les garçons pré-pubères avant traitement chimio-radiothérapique.

Il a été montré que certaines étapes de la méiose ont pu être réaliséesin vitro, avec obtention de spermatides à partir de spermatocytes de rats. Des spermatides rondes cryoconservées ont été utilisées pour féconder des ovocytes de souris et ont permis d’obtenir des souriceaux. Dans l’espèce humaine, des grossesses ont pu être obtenues à la suite de microinjections de spermatides rondes dans des cas d’azoospermie. Une grossesse a été rapportée en utilisant une spermatide ayant subi une cryoconservation. Ainsi le projet de prélèvement d’un fragment de parenchyme testiculaire avant traitement stérilisant, de maturationin vitro des spermatogonies jusqu’au stade de spermatide, de cryoconservation des spermatides, et de leur utilisation ultérieure pour microinjection intra-ovocytaire dans le but d’obtenir une grossesse, n’apparaît plus irréalisable, puisque chaque étape a pu être réalisée individuellement. La mise au point chez l’animal d’une telle procédure apparaît un préalable indispensable pour en étudier la faisabilité mais aussi l’innocuité avant le passage à une phase d’application clinique.

Abstract

Sperm auto-conservation before chimioradiotherapy allows preservation of future reproductive possibilities in case of malignancy in young adult male. Because of the lack of mature spermatozoa, such possibilities cannot be offered for boys before puberty, even though the rate of cure of childhood malignancies is high. This paper reviewed recent advances in reproductive technology, which open the field of withdrawal of immature germ cells in prepubertal boys for in vitro maturation and cryopreservation for future paternity. It has been shown that the main steps of male meiosis have been driven in vitro, allowing to obtain round spermatids from pachytene spermatocytes in the rat. In mice, cryopreserved round spermatids have been used for oocyte fertilization and gave rise to normal living pups. In humans pregnancies and living babies have been reported after microinjection of round spermatids in cases of azoospermia. One pregnancy has been obtained with a cryopreserved spermatid. Thus the project of withdrawal of testicular tissues before sterilizing treatment, in vitro maturation of spermatogonia into round spermatids and cryopreservation of immature germ cells for future use for assisted fertilization does not seem unrealistic since each step has been done individually. However developing animal models is necessary to study not only the efficiency of the whole procedure but also to check its harmlessness before clinical trials.

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Lejeune, H., Durand, P. Conservation de tissu testiculaire et maturation in vitro de la lignée germinale pour préservation du potentiel de reproduction avant traitement anticancéreux chez le garçon pré-pubère. Androl. 9, 498–504 (1999). https://doi.org/10.1007/BF03034667

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