title: Defining the human sperm microtubulome: an integrated genomics approach.
abstract: Sperm motility notably depends on the structural integrity of the flagellum and the regulation of microtubule dynamics. Although researchers have started to use "omics" techniques to characterize the human sperm's molecular landscape, the constituents responsible for the assembly, organization, and dynamics of the flagellum microtubule have yet to be fully defined. In this study, we defined a core set of 116 gene products associated with the human sperm microtubulome (including products potentially involved in abnormal ciliary phenotypes and male infertility disorders). To this end, we designed and applied an integrated genomics workflow and combined relevant proteomics, transcriptomics, and interactomics datasets to reconstruct a dynamic interactome map. By further integrating phenotypic information, we defined a disease-interaction network; this enabled us to highlight a number of novel factors potentially associated with altered sperm motility and male fertility. Lastly, we experimentally validated the expression pattern of two candidate genes (CUL3 and DCDC2C) that had never previously been associated with male germline differentiation. Our analysis suggested that CUL3 and DCDC2C's products have important roles in the sperm flagellum. Taken as a whole, our results demonstrate that an integrated genomics strategy can highlight relevant molecular factors in specific sperm components. This approach could be easily extended by including other "omics" data (from asthenozoospermic men, for example) and identifying other critical proteins from the human sperm microtubulome.
authors.affiliation: EA 4308, Department of Reproductive Biology and Spermiology-CECOS, Lille University Medical Center, Lille, France.|INSERM UMR 837-1, Alzheimer & Tauopathies, Jean-Pierre Aubert Research Center, Lille, France.
authors.forename: Fanny
authors.initials: F
authors.lastname: Jumeau
authors.affiliation: INSERM U1085-IRSET, 9 avenue du Professeur Léon Bernard, Rennes, France.
authors.forename: Frédéric
authors.initials: F
authors.lastname: Chalmel
authors.affiliation: INSERM UMR 837-1, Alzheimer & Tauopathies, Jean-Pierre Aubert Research Center, Lille, France.
authors.forename: Francisco-Jose
authors.initials: FJ
authors.lastname: Fernandez-Gomez
authors.affiliation: INSERM UMR 837-1, Alzheimer & Tauopathies, Jean-Pierre Aubert Research Center, Lille, France.
authors.forename: Céline
authors.initials: C
authors.lastname: Carpentier
authors.affiliation: INSERM UMR 837-1, Alzheimer & Tauopathies, Jean-Pierre Aubert Research Center, Lille, France.
authors.forename: Hélène
authors.initials: H
authors.lastname: Obriot
authors.affiliation: BioImaging Center Lille-Nord de France, School of Medicine, University of Lille 2, Lille, France.
authors.forename: Meryem
authors.initials: M
authors.lastname: Tardivel
authors.affiliation: INSERM UMR 837-1, Alzheimer & Tauopathies, Jean-Pierre Aubert Research Center, Lille, France.
authors.forename: Marie-Laure
authors.initials: ML
authors.lastname: Caillet-Boudin
authors.affiliation: EA 4308, Andrology Unit, Lille University Medical Center, Lille, France.
authors.forename: Jean-Marc
authors.initials: JM
authors.lastname: Rigot
authors.affiliation: EA 4308, Reproductive Biology Laboratory-CECOS, Rouen University Medical Center, and Institute for Biomedical Research, University of Rouen, Rouen, France.
authors.forename: Nathalie
authors.initials: N
authors.lastname: Rives
authors.affiliation: INSERM UMR 837-1, Alzheimer & Tauopathies, Jean-Pierre Aubert Research Center, Lille, France.
authors.forename: Luc
authors.initials: L
authors.lastname: Buée
authors.affiliation: INSERM UMR 837-1, Alzheimer & Tauopathies, Jean-Pierre Aubert Research Center, Lille, France.
authors.forename: Nicolas
authors.initials: N
authors.lastname: Sergeant
authors.affiliation: EA 4308, Department of Reproductive Biology and Spermiology-CECOS, Lille University Medical Center, Lille, France.
authors.forename: Valérie
authors.initials: V
authors.lastname: Mitchell
mesh_terms: D044842:Cullin Proteins / Q000378:metabolism; D005407:Flagella / Q000378:metabolism; D023281:Genomics; D006801:Humans; D008297:Male; D008540:Meiosis; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D008870:Microtubules / Q000378:metabolism*; D060066:Protein Interaction Maps; D020543:Proteome; D013094:Spermatozoa / Q000378:metabolism*
chemical_list: C503645:CUL3 protein, human; D044842:Cullin Proteins; C510451:DCDC2 protein, human; D008869:Microtubule-Associated Proteins; D020543:Proteome
keywords: CUL3; DCDC2C; human sperm; integrated genomics; microtubulome