Journal of Assisted Reproduction and Genetics

, Volume 36, Issue 1, pp 69–77 | Cite as

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

  • Fatma AbdelhediEmail author
  • Céline Chalas
  • Jean-Maurice Petit
  • Nouha Abid
  • Elyes Mokadem
  • Syrine Hizem
  • Hassen Kamoun
  • Leila Keskes
  • Jean-Michel Dupont
Gamete Biology



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.


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.


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.


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.


Globozoospermia DPY19L2 gene Chromatin organization Three-dimensional fluorescence in situ hybridization (3D-FISH) Nuclear lamina 



We would like to thank Jean-Maurice Petit for technical assistance in 3D-FISH analysis, and Céline Chalas, Nouha Abid and Elyes Mokadem for access to patient and healthy control samples. We are grateful to the Service Commun de Microscopie in Paris Descartes University.

Compliance with ethical standards

Conflict of interest

The authors declare that there are no conflicts of interest.

Supplementary material

10815_2018_1342_Fig6_ESM.png (593 kb)
Fig A1

Serial optical sections of control sperm nucleus and chromocenters (sections were made every 0.3 μm). (A) gray-scale images; (B) RGB images. 3D-FISH was performed using Human Chromosome Pan-Centromeric probe (green) (PNG 592 kb)

10815_2018_1342_MOESM1_ESM.tiff (1.2 mb)
High resolution image (TIFF 1206 kb)
10815_2018_1342_Fig7_ESM.png (547 kb)
Fig A2

Serial optical sections of globozoospermic sperm nucleus and chromocenters (sections were made every 0.3 μm). (A) gray-scale images; (B) RGB images. 3D-FISH was performed using Human Chromosome Pan-Centromeric probe (green) (PNG 546 kb)

10815_2018_1342_MOESM2_ESM.tiff (1.3 mb)
High resolution image (TIFF 1316 kb)
10815_2018_1342_Fig8_ESM.png (563 kb)
Fig A3

Serial optical sections of control sperm nucleus and chromosome X territory (sections were made every 0.3 μm). (A) gray-scale images; (B) RGB images. 3D-FISH was performed using WCPX probe (red) (PNG 563 kb)

10815_2018_1342_MOESM3_ESM.tiff (1.1 mb)
High resolution image (TIFF 1121 kb)
10815_2018_1342_Fig9_ESM.png (612 kb)
Fig A4

Serial optical sections of globozoospermic sperm nucleus and chromosome X territory (sections were made every 0.3 μm). (A) gray-scale images; (B) RGB images. 3D-FISH was performed using WCPX probe (red) (PNG 612 kb)

10815_2018_1342_MOESM4_ESM.tiff (1.4 mb)
High resolution image (TIFF 1457 kb)


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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Génomique, Epigénétique et Physiopathologie de la Reproduction, U1016 INSERM-UMR 8104 CNRS, Institut CochinUniversité Paris DescartesParisFrance
  2. 2.Laboratoire de CytogénétiqueHôpital Cochin, APHPParisFrance
  3. 3.Laboratoire de Génétique Moléculaire HumaineFaculté de Médecine de SfaxSfaxTunisie
  4. 4.Laboratoire d’Histologie Embryologie - Biologie de la ReproductionHôpital Cochin, APHPParisFrance
  5. 5.Sorbonne Paris CitéUniversité Paris DescartesParisFrance
  6. 6.Centre d’Aide Médicale à la ProcréationPolyclinique Ibn NafissSfaxTunisie
  7. 7.Centre d’Aide Médicale à la ProcréationPolyclinique El AliaSfaxTunisie

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