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Altérations morphologiques des spermatozoïdes en microscopie électronique: indications, phénotypes, fécondance, et pronostic de fertilité

Ultrastructural morphological sperm abnormalities: indications, phenotypes, and fertility potential

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L’analyse conventionnelle du sperme (spermogramme) est limitée à l’analyse des spermatozoïdes au grossissement x1000, et il y a des situations, rares, où ce grossissement est insuffisant. L’étude des spermatozoïdes en microscopie électronique permet d’étudier les organites du spermatozoïde à un grossissement important (x100 000), et de quantifier les anomalies des constituants impliqués dans la fécondance et l’aptitude migratoire des spermatozoïdes. Les indications d’un examen de la morphologie des spermatozoïdes en microscopie électronique sont très peu nombreuses: cette étude est réservée 1) au cas de tératospermies sévères monomorphes et stables (globozoospermie = spermatozoïdes à tête ronde sans acrosome,pinheads = spermatozoïdes décapités ou sans tête), 2) en cas d’altération partielle (asthénospermie) ou totale (akinétospermie) de la mobilité et/ou de la qualité du mouvement des spermatozoïdes. Dans tous les cas, l’homme présente une infertilité primaire. La globozoospermie et lespinheads sont détectés en microscopie optique.

L’intérêt de l’étude des spermatozoïdes en microscopie électronique est de déterminer précisément et de quantifier les structures anormales. Les phénotypes pathologiques ont une expression hétérogène. Des organites du spermatozoïde autres que ceux primitivement impliqués dans les phénotypes pathologiques peuvent également présenter des altérations. La globozoospermie est généralement caractérisée par une absence d’élongation du noyau, d’acrosome et du feuillet post-acrosomique. Dans les spermatozoïdes décapités, on observe le plus souvent l’absence de la fossette d’implantation et de la plaque basale.

L’asthénospermie peut être l’indication d’une étude des spermatozoïdes en microscopie électronique, lorsqu’elle n’est pas associée à la nécrospermie. Dans les Dysplasies de la gaine fibreuse (DFS), les spermatozoïdes présentent généralement un flagelle court et une mobilité totale très faible, inférieure à 5%. Les phénotypes, variés, sont caractérisés par des anomalies de l’arrangement des composants de la gaine fibreuse. Vingt pour cent des patients ont des pathologies du tractus respiratoire. Dans les Dyskinésies ciliaires primitives (DCP), les spermatozoïdes sont souvent immobiles et présentent une morphologie normale en microscopie optique. A coté de la forme complète où l’axonème est absent, on observe des formes incomplètes avec absence des bras de dynéine, des doublets périphériques, des microtubules.

La prévalence de ces phénotypes dans la population des hommes infertiles est rare. L’incidence familiale, la consanguinité parentale, ainsi que l’incidence d’une zone géographique sont fréquentes, ce qui suggère l’existence d’un ou plusieurs substrats génétiques. Malgré les connaissances actuelles fragmentaires, une information génétique sur la possibilité de transmission du phénotype anormal à la descendance doit être délivrée au couple.

Tous ces hommes présentant ces phénotypes sont spontanément infertiles. La seule alternative de fécondation est la technique de microinjection intracytoplasmique d’un spermatozoïde dans l’ovocyte (ICSI). D’après la littérature et notre expérience, les résultats de l’ICSI avec les spermatozoïdes appartenant à ces phénotypes sont moins bons que ceux de l’ICSI en général.

La microscopie électronique est non seulement un outil diagnostique dans l’infertilité masculine sévère, mais également un outil pronostique du succès de la prise en charge en ICSI qui sera évaluée pour chaque cas.

Abstract

Conventional semen analysis (sperm count) is limited to examination of spermatozoa at a magnification of x1,000, which may be insufficient in rare situations. Electron microscopy sperm examination allows high-power (x 100,000) analysis of sperm organelles and quantification of abnormalities of the constituents involved in sperm mobility and fertility potential. Electron microscopy sperm morphology examination is rarely indicated and is reserved to: 1) severe monomorphic and stable teratospermia (globozoospermia = spermatozoa with a round head and no acrosome, pinheads = decapitated spermatozoa), 2) partial (asthenospermia) or total (akinetospermia) alteration of sperm mobility and/or quality of sperm movement. All of these anomalies are associated with primary infertility. Globozoospermia and pinheads can be detected by light microscopy.

Electron microscopy sperm morphology examination precisely identifies and quantifies sperm abnormalities. Pathological phenotypes have a heterogeneous expression. The organelles of spermatozoa other than those primarily involved in the pathological phenotype may also present alterations. Globozoospermia is generally characterized by the absence of elongation of the nucleus, and absence of the acrosome and the post-acrosomal region. The implantation fossa and basal plate are generally missing in decapitated spermatozoa.

Asthenospermia may be an indication for electron microscopy sperm examination when it is not associated with necrospermia. Sperm with fibrous sheath dysplasia (FSD) generally present a short flagella and very low overall mobility, less than 5%. The various phenotypes are characterized by abnormal arrangements of the constituents of the fibrous sheath and 20% of patients also present respiratory tract disease. In primary ciliary dyskinesia (PCD), spermatozoa are often immobile and present a normal morphology on light microscopy. Apart from the complete form with absent axoneme, incomplete forms are also observed with absence of the dynein arms, peripheral doublets, microtubules.

These phenotypes have a low prevalence in the population of infertile men. A familial incidence, parental consanguinity, and a high incidence in certain geographical regions are frequently reported, suggesting the existence of one or several genetic mechanisms. Despite the limited state of knowledge at the present time, couples must be informed about the possible transmission of the phenotype to their descendants.

All men with these phenotypes are spontaneously infertile. The only alternative fertilization technique is intracytoplasmic sperm injection (ICSI). According to the literature and our own experience, the results of ICSI with sperm presenting these phenotypes are poorer than those of ICSI in general.

Electron microscopy is not only a diagnostic tool in severe male infertility, but also a prognostic indicator of the success of management by ICSI, which must be evaluated for each case.

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Correspondence to Valérie Mitchell or Marie-Claire Peers or Carole Marchetti or Maryse Leroy or Jean -Marc Rigot or Jean -Jacques Lafitte or Alexandre Moerman or Denise Escalier.

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Mots Clés

  • microscopie électronique
  • globozoospermie
  • spermatozoïdes décapités
  • dysplasie de la gaine fibreuse
  • dyskinésie ciliaire primitive
  • ICSI

Key Words

  • electron microscopy
  • globozoospermia
  • pinheads
  • fibrous sheath dysplasia
  • primary ciliary dyskinesia
  • ICSI