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Sci Rep. 2017 Jan 3;7:39760. doi: 10.1038/srep39760.

Induced pluripotent stem cell generation from a man carrying a complex chromosomal rearrangement as a genetic model for infertility studies.

Author information

1
AP-HP, Service d'Histologie, Embryologie et Cytogénétique, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.
2
Université Paris-Sud, 94276 Le Kremlin-Bicêtre cedex, France.
3
AP-HP, Service de Gynécologie-Obstétrique et Médecine de la Reproduction, Hôpitaux Universitaires Paris-Sud, Hôpital Antoine Béclère, 92140, Clamart, France.
4
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.
5
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.

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.

PMID:
28045072
PMCID:
PMC5206619
DOI:
10.1038/srep39760
[Indexed for MEDLINE]
Free PMC Article

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