Les mutations de DNAH17 causent une infertilité isolée par asthénospermie par défaut d’une dynéine axonémale spécifique du flagelle des spermatozoïdes - Inserm - Institut national de la santé et de la recherche médicale Access content directly
Conference Papers Year : 2020

Les mutations de DNAH17 causent une infertilité isolée par asthénospermie par défaut d’une dynéine axonémale spécifique du flagelle des spermatozoïdes

Lucie Thomas
Guy Montantin
Sylvie Tissier
Bruno Copin
  • Function : Author
  • PersonId : 1176543
  • IdHAL : bruno-copin
Sandra Chantot-Bastaraud
Florence Dastot - Le Moal
Anne Loyens
  • Function : Author
  • PersonId : 858325
Aminata Touré

Abstract

Motile cilia and sperm flagella share an evolutionarily conserved axonemal structure. Their structural and/or functional defects are associated with primary ciliary dyskinesia (PCD), a genetic disease characterized by chronic respiratory-tract infections and in which most males are infertile due to asthenozoospermia. Among the well-characterized axonemal protein complexes, the outer dynein arms (ODAs), through ATPase activity of their heavy chains (HCs), play a major role for cilia and flagella beating. However, the contribution of the different HCs (gtype: DNAH5 and DNAH8 and btype: DNAH9, DNAH11, and DNAH17) in ODAs from both organelles is unknown. By analyzing five male individuals who consulted for isolated infertility and displayed a loss of ODAs in their sperm cells but not in their respiratory cells, we identified bi-allelic mutations in DNAH17. The isolated infertility phenotype prompted us to compare the protein composition of ODAs in the sperm and ciliary axonemes from control individuals. We show that DNAH17 and DNAH8, but not DNAH5, DNAH9, or DNAH11, colocalize with a-tubulin along the sperm axoneme, whereas the reverse picture is observed in respiratory cilia, thus explaining the phenotype restricted to sperm cells. We also demonstrate the loss of function associated with DNAH17 mutations in two unrelated individuals by performing immunoblot and immunofluorescence analyses on sperm cells; these analyses indicated the absence of DNAH17 and DNAH8, whereas DNAH2 and DNALI, two inner dynein arm components, were present. Overall, this study demonstrates that mutations in DNAH17 are responsible for isolated male infertility and provides information regarding ODA composition in human spermatozoa.
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inserm-03951614 , version 1 (23-01-2023)

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  • HAL Id : inserm-03951614 , version 1

Cite

Lucie Thomas, Marjorie Whitfield, Émilie Béquignon, Alain Schmitt, Laurence Stouvenel, et al.. Les mutations de DNAH17 causent une infertilité isolée par asthénospermie par défaut d’une dynéine axonémale spécifique du flagelle des spermatozoïdes. Assises de génétique humaine et médicale, Jan 2020, Tours, France. ⟨inserm-03951614⟩
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