• PMID: 30362053
• Gene Name: DPY19L2
• Condition: Globozoospermia, Male infertility
• Association: Associated
• Sex: Male
• Infertility type: Male infertility
• Other associated phenotypes: Globozoospermia, Male infertility

Altered three-dimensional organization of sperm genome in DPY19L2-deficient globozoospermic patients

Abdelhedi F, Chalas C, Petit JM, Abid N, Mokadem E, Hizem S, Kamoun H, Keskes L, Dupont JM.

PURPOSE: To explore the three-dimensional (3D) organization of sperm genome in DPY19L2-deficient globozoospermic patients speculating a link between DPY19L2 and genome organization of sperm nucleus. METHODS: This is a study of chromatin organization in DPY19L2-deficient globozoospermic patients and healthy donors using three-dimensional fluorescence in situ hybridization (3D-FISH) combined with confocal laser scanning microscopy followed by 3D image analysis. The 3D structures of sperm nuclei, chromocenter, telomeric regions and chromosome territories (CTs), were reconstructed using IMARIS software, and the relative radial position for each individual signal was calculated. Statistical analysis used a non-parametric Mann-Whitney test was appropriate with significance at p < 0.05. RESULTS: DPY19L2-deficient globozoospermic patients display impaired sperm chromocenter organization resulting in an increased number of chromocenters (5.4 vs 3.5; p < 0.0001). Moreover, radial positions of telomeres are modified with a more central position in globozoospermic nuclei. 3D-FISH analysis of five chromosome territories (CTs) (X, Y, 7, 17, 18) showed that DPY19L2-deficient globozoospermic sperm nuclei display altered spatial organization of CT X, CT 7 and CT 18. CONCLUSIONS: Our findings strengthen the hypothesis that DPY19L2 might be considered as a LINC-like protein having a crucial role in the organization of nuclear chromatin in sperm nucleus through its interaction with nuclear lamina. Our results might also explain defective embryonic development after intracytoplasmic sperm injection (ICSI) performed with DPY19L2-deficient globozoospermic sperm. FAU - Abdelhedi, Fatma AU - Abdelhedi F AUID- ORCID: 0000-0001-5088-8384 AD - Génomique, Epigénétique et Physiopathologie de la Reproduction, U1016 INSERM-UMR 8104 CNRS, Institut Cochin, Université Paris Descartes, Paris, France. abdelhedi_f@yahoo.fr. AD - Laboratoire de Cytogénétique, Hôpital Cochin, APHP, 75014, Paris, France. abdelhedi_f@yahoo.fr. AD - Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Sfax, Tunisie. abdelhedi_f@yahoo.fr. FAU - Chalas, Céline AU - Chalas C AD - Laboratoire d'Histologie Embryologie - Biologie de la Reproduction, Hôpital Cochin, APHP, 75014, Paris, France. FAU - Petit, Jean-Maurice AU - Petit JM AD - Sorbonne Paris Cité, Université Paris Descartes, Paris, France. FAU - Abid, Nouha AU - Abid N AD - Centre d'Aide Médicale à la Procréation, Polyclinique Ibn Nafiss, Sfax, Tunisie. FAU - Mokadem, Elyes AU - Mokadem E AD - Centre d'Aide Médicale à la Procréation, Polyclinique El Alia, Sfax, Tunisie. FAU - Hizem, Syrine AU - Hizem S AD - Laboratoire de Cytogénétique, Hôpital Cochin, APHP, 75014, Paris, France. FAU - Kamoun, Hassen AU - Kamoun H AD - Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Sfax, Tunisie. FAU - Keskes, Leila AU - Keskes L AD - Laboratoire de Génétique Moléculaire Humaine, Faculté de Médecine de Sfax, Sfax, Tunisie.