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  • Vieillissement 0652 0147 V
  • Vieillissement et Reproduction
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Influence du vieillessement sur la spermatogenèse: étude histologique et cytogénétique moléculaire au niveau testiculaire chez 46 sujets âgés de 29 à 102 ans

Influence of ageing on spermatogenesis: testicular histomorphometric and cytogenetic study in elderly men (61 to 102 years)

Andrologie volume 14, pages 197–205 (2004)Cite this article

Resume

L'effet délétère de l'âge maternel sur le risque d'anomalie méiotique est bien établi, mais il n'en est pas de même pour l'effet de l'âge paternel. Nous avons étudié l'influence du vieillissement sur la spermatogenèse évaluée par l'histologie testiculaire évaluée par histomorphomètrie et sur le taux d'anomalies méiotiques testiculaires évalué par la technique d'hybridation in situ fluorescente (FISH) pour les chromosomes X, Y et 18. L'étude a comporté 46 hommes âgés de 29 à 102 ans (36 sujets âgés et 10 témoins). L'analyse histomorphomètrique des biopsies testiculaires a concerné les tubes séminifères: surface, épaisseur de la membrane propre, densité en cellules de Sertoli, en spermatogonies, en spermatocytes et en spermatozoïdes, ainsi que le tissu interstitiel: nombre de groupements des cellules de Leydig par champ, surface occupée par les cellules de Leydig, et densité. Cette étude nous a permis de classer les sujets âgés (n=36) en trois groupes: 17 sujets âgés de 61 à 95 ans à spermatogenèse complète (groupe 1), 4 sujets à spermiogenèse arrêtée (groupe 2) et 15 sujets avec un arrêt précoce de la spermatogenèse (cellules diploïdes) (groupe 3). Les variations interindividuelles étaient très importantes. L'épaisseur de la membrane propre paraît être le paramètre le mieux corrélé à la conservation de la spermatogenèse. Nous avons analysé par FISH un total de 10000 cellules postméiotiques dont 4738 cellules post méiotiques dans le groupe 1 et un total de 4882 cellules post méiotiques chez les sujets jeunes témoins. Les taux des cellules normales haploïdes X18 et Y18 représentent respectivement 50,76% et 47,95% dans le groupe de sujets âgés (groupe 1), 50,35% et 48,55% dans le groupe des témoins. Le taux d'aneuploïdie totale est de 1,29% chez les sujets âgés du groupe 1 et de 1,10% chez le groupe témoin. Pour le groupe 2 (sujets avec un arrêt de la spermiogenèse), les pourcentages de cellules X18, Y18 et le taux d'aneuploïdie étaient respectivement 47,96%, 37,75% et 14,28% au niveau des spermatides (n=98). Ce taux d'anomalies de 14,28% est significativement accru, comparé aux résultats du groupe 1 et des témoins.

Au total nous avons conclu qu'une spermatogenèse peut être conservée à un âge très avancé (95 ans), que le taux d'aneuploïdie postméiotique des sujets âgés à spermatogenèse complète n'est pas globalement différent de celui qui est observé chez des sujets jeunes témoins et que l'incidence des aneuploïdies post-méiotiques semble être plus élevée lorsque la spermiogenèse est arrêtée (14,28%versus 1,10%).

Abstract

The harmful effect of maternal age on abnormal meiotic behaviour has been clearly established, but little is known about the effect of paternal age on chromosome malsegregations and the results of studies on this question are fairly controversial. The purpose of this study was to evaluate the influence of ageing on testicular histology and aneuploidy rate in testicular post-meiotic cells. A possible age-related risk has been suggested by the increased frequency of medical assisted reproduction techniques for older men.

We analysed 36 testicular samples from subjects aged 61–102 years by histology and histomorphometry. We examined testicular cells with fluorescence in situ hybridisation (FISH). We studied six histological sections (20 cross-sectioned tubules) by computer-assisted morphometric analysis (Histolab). The study was based on the following parameters: for seminiferous tubules: surface area, thickness of the basement membrane, nucleus density (Sertoli cells, spermatogonia, spermatocytes and spermatozoids); for interstitial tissue: cluster number and surface area occupied by the Leydig cells, nucleus density. We analysed cells by FISH and a set of three probes X, Y and 18 (Abboto). The results were compared to those of a control group of testicular biopsies from 10 subjects (29–40 years) with obstructive azoospermia and normal histology.

Results: The histomorphometric study showed various alterations including: thickening of the basement membrane when spermatogenesis was arrested. The number of germinal cells and the number of Sertoli cells decreased with increasing age and Leydig cell hypertrophy was observed with increasing age. Complete spermatogenesis was observed in men up to the age of 95 years old. The most sensitive step was pachytene. Spermatogonia can persist until the age of 98 years. The 36 elderly men were divided into 3 groups: preserved spermatogenesis (17 subjects; group 1), arrested spermatogenesis (4 subjects; group 2) and early disrupted spermatogenesis with only diploid cells or no cells (15 subjects; group 3).

For the control group, post-meiotic cells (n=4,882) showed 50.35% X18, 48.55% Y18 and 1.1% of cells with aneuploidy. For elderly subjects with preserved spermatogenesis, post-meiotic cell analysis (n=4,738) showed 50.76% X18, 47.95% Y18 and 1.29% of cells with aneuploidy. Subjects with arrested spermatogenesis presented 47.96% X18, 37.75%Y18 and the aneuploidy rate among spermatids (n=98) was 14.28%. This rate was higher than those observed in controls and in group 1. In conclusion, we observed that spermatogenesis was possible until an advanced age (95 years). There appears to be an increased incidence of post-meiotic aneuploidy in the case of arrested spermatogenesis (14.28 vs 1.10%). The aneuploidy rate in the group of subjects with preserved spermatogenesis was not statistically different from that observed in the control group.

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Authors and Affiliations

  1. Laboratoire CEREPP, Paris

    Olivier Cussenot

  2. CHI Poissy Service Histo-Embryologie-Biologie de la Reproduction-Cytogénétique, Poissy

    Marianne Bergere, Martine Albert, Nathalie Ledee, François Vialard & Jacqueline Selva

  3. INSERM Unité 407, Oulins

    Marianne Bergere, Martine Albert, François Vialard & Jacqueline Selva

  4. Laboratoire d'Histologie Embryologie, UFR des Saint Pères, Université Paris V, 45 rue des Saints Pères, 75270, Paris Cedex 06

    Mbarka Dakouane, Lucia Bicchieray, Marianne Bergere, Martine Albert & Jacqueline Selva

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Dakouane, M., Bicchieray, L., Bergere, M. et al. Influence du vieillessement sur la spermatogenèse: étude histologique et cytogénétique moléculaire au niveau testiculaire chez 46 sujets âgés de 29 à 102 ans. Androl. 14, 197–205 (2004). https://doi.org/10.1007/BF03034795

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Basic and Clinical Andrology

ISSN: 2051-4190