L’infertilité masculine: Nos connaissances ne doivent pas faire oublier notre ignorance

Université Paris V INSERUM U567, Institut Cochin Paris France; Hôpital Cochin Laboratoire de Biochimie et génétique Moléculaire 123 boulevard de Port-Royal. 75014 Paris France
Andrologie 13(2):158-160. DOI: 10.1007/BF03034430

ABSTRACT Environ 15% des couples dans le monde sont concernés par des problèmes de procréation. Dans 20% des cas, c’est l’homme seul
qui est en cause. Dans 20% de ces cas, une cause génétique peut être identifiée. Les principales causes peuvent se classer
en trois grandes catégories: i) les anomalies chromosomiques, ii) les microdélétions du bras long du chromosomes Y et iii)
les mutations du gèneCFTR. Toutefois, malgré les progrès considérables réalisés au cours de ces dernières années, la cause de l’infertilité est ignorée
dans un grand nombre de cas. Le développement des stratégies gène candidat, les analyses de liaison généntique dans des formes
familiales d’infertilité masculine, la création de modèles animaux ainsi que les études du remodelage de la chromatine au
cours de la spermiogénèse devraient permettre d’identifier à court terme de nouveaux facteurs généntiques, qui chez l’homme
sont à l’origine de stérilité.
About 15% of couples worldwide are affected by reduced fertility. In 20% of cases of couple infertility, the problem can be
predominantly attributed to the male. In 20% of cases, a genetic cause of male infertility can usually be identified. The
main genetic causes are: autosomal and sex chromosomal abnormalities, microdeletions within regions of the Y-chromosome containing
candidate gene families for spermatogenesis and mutations in theCFTR gene. However, despite enormous progress in the understanding of human reproductive physiology, the underlying cause of male
infertility often cannot be elucidated. Candidate gene strategies, linkage analysis in large familial forms of male infertility,
targeted mutagenesis in the mouse and studies of chromatin reorganization during spermatid maturation should provide rapid
progress in our understanding of the genetic factors that contribute to male infertility, which may open up new approaches
to the treatment of this condition.

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    ABSTRACT: During spermiogenesis (the maturation of spermatids into spermatozoa) in many vertebrate species, protamines replace histones to become the primary DNA-packaging protein. It has long been thought that this process is facilitated by the hyperacetylation of histone H4. However, the responsible histone acetyltransferase enzymes are yet to be identified. CDY is a human Y-chromosomal gene family expressed exclusively in the testis and implicated in male infertility. Its mouse homolog Cdyl, which is autosomal, is expressed abundantly in the testis. Proteins encoded by CDY and its homologs bear the "chromodomain," a motif implicated in chromatin binding. Here, we show that (i) human CDY and mouse CDYL proteins exhibit histone acetyltransferase activity in vitro, with a strong preference for histone H4; (ii) expression of human CDY and mouse Cdyl genes during spermatogenesis correlates with the occurrence of H4 hyperacetylation; and (iii) CDY and CDYL proteins are localized to the nuclei of maturing spermatids where H4 hyperacetylation takes place. Taken together, these data link human CDY and mouse CDYL to the histone-to-protamine transition in mammalian spermiogenesis. This link offers a plausible mechanism to account for spermatogenic failure in patients bearing deletions of the CDY genes.
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    Human Mutation 07/2000; 16(2):143 - 156. · 5.05 Impact Factor