title: Induced pluripotent stem cell generation from a man carrying a complex chromosomal rearrangement as a genetic model for infertility studies.
abstract: Despite progress in human reproductive biology, the cause of male infertility often remains unknown, due to the lack of appropriate and convenient in vitro models of meiosis. Induced pluripotent stem cells (iPSCs) derived from the cells of infertile patients could provide a gold standard model for generating primordial germ cells and studying their development and the process of spermatogenesis. We report the characterization of a complex chromosomal rearrangement (CCR) in an azoospermic patient, and the successful generation of specific-iPSCs from PBMC-derived erythroblasts. The CCR was characterized by karyotype, fluorescence in situ hybridization and oligonucleotide-based array-comparative genomic hybridization. The CCR included five breakpoints and was caused by the inverted insertion of a chromosome 12 segment into the short arm of one chromosome 7 and a pericentric inversion of the structurally rearranged chromosome 12. Gene mapping of the breakpoints led to the identification of a candidate gene, SYCP3. Erythroblasts from the patient were reprogrammed with Sendai virus vectors to generate iPSCs. We assessed iPSC pluripotency by RT-PCR, immunofluorescence staining and teratoma induction. The generation of specific-iPSCs from patients with a CCR provides a valuable in vitro genetic model for studying the mechanisms by which chromosomal abnormalities alter meiosis and germ cell development.
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.|Université Paris-Sud, 94276 Le Kremlin-Bicêtre cedex, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Mouka
authors.affiliation: AP-HP, Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.
authors.forename: Vincent
authors.initials: V
authors.lastname: Izard
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.|Université Paris-Sud, 94276 Le Kremlin-Bicêtre cedex, France.
authors.forename: Gérard
authors.initials: G
authors.lastname: Tachdjian
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.|Université Paris-Sud, 94276 Le Kremlin-Bicêtre cedex, France.
authors.forename: Sophie
authors.initials: S
authors.lastname: Brisset
authors.affiliation: Sup'Biotech Villejuif 94800, Commissariat à l'Energie Atomique et aux Énergies Alternatives, Institute of Emerging Diseases and Innovative Therapies (iMETI), SEPIA, 92265 Fontenay-aux-Roses, France.
authors.forename: Frank
authors.initials: F
authors.lastname: Yates
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.
authors.forename: Anne
authors.initials: A
authors.lastname: Mayeur
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.
authors.forename: Loïc
authors.initials: L
authors.lastname: Drévillon
authors.affiliation: Sup'Biotech Villejuif 94800, Commissariat à l'Energie Atomique et aux Énergies Alternatives, Institute of Emerging Diseases and Innovative Therapies (iMETI), SEPIA, 92265 Fontenay-aux-Roses, France.
authors.forename: Rafika
authors.initials: R
authors.lastname: Jarray
authors.affiliation: Commissariat à l'Energie Atomique et aux Énergies Alternatives, Institute of Emerging Diseases and Innovative Therapies (iMETI), 92265 Fontenay-aux-Roses; UMR-E 007, Université Paris-Saclay, 91400 Orsay; INSERM, 75013 Paris, France.
authors.forename: Philippe
authors.initials: P
authors.lastname: Leboulch
authors.affiliation: Commissariat à l'Energie Atomique et aux Énergies Alternatives, Institute of Emerging Diseases and Innovative Therapies (iMETI), 92265 Fontenay-aux-Roses; UMR-E 007, Université Paris-Saclay, 91400 Orsay; INSERM, 75013 Paris, France.
authors.forename: Leila
authors.initials: L
authors.lastname: Maouche-Chrétien
authors.affiliation: AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.|Université Paris-Sud, 94276 Le Kremlin-Bicêtre cedex, France.
authors.forename: Lucie
authors.initials: L
authors.lastname: Tosca
mesh_terms: D000328:Adult; D001284:Atrophy; D018797:Cell Cycle Proteins; D002454:Cell Differentiation; D002478:Cells, Cultured; D000067470:Cellular Reprogramming Techniques; D007446:Chromosome Inversion / Q000235:genetics; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D055028:Comparative Genomic Hybridization; D004268:DNA-Binding Proteins; D004900:Erythroblasts / Q000502:physiology*; D005260:Female; D056726:Genetic Association Studies; D006801:Humans; D017404:In Situ Hybridization, Fluorescence; D057026:Induced Pluripotent Stem Cells / Q000502:physiology*; D007248:Infertility, Male / Q000235:genetics / Q000473:pathology*; D007621:Karyotyping; D008297:Male; D008540:Meiosis / Q000235:genetics; D009687:Nuclear Proteins / Q000235:genetics*; D029082:Sendai virus / Q000235:genetics*; D013090:Spermatocytes / Q000502:physiology*; D013737:Testis / Q000473:pathology*
chemical_list: D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C490060:SYCP3 protein, human