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

Abstract

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 threedimensional 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.

Meiotic Nuclear Architecture in Distinct Mole Vole Hybrids with Robertsonian Translocations: Chromosome Chains, Stretched Centromeres, and Distorted Recombination

“…Heterochromatic compartments play a significant role in the nucleus content [ 119 ]. However, gene mutations and chromatin and chromosomal rearrangements can change the intranuclear organization, which can lead to diseases and the appearance of various abnormal manifestations [ 120 , 121 , 122 , 123 , 124 , 125 ].…”

Human Sperm Chromosomes: To Form Hairpin-Loops, Or Not to Form Hairpin-Loops, That Is the Question

“…Several studies have reported perturbations, albeit often modest alterations in the positioning of various target loci. Alterations have been reported in patients exhibiting semen parameter disturbances and/or increased sperm aneuploidy [15,19,56,57], increased levels of DNA damage or nuclear perturbations such as sperm nuclear vacuoles [58,59], or carriers of chromosome translocations [45]. There are also inherent methodological differences between studies.…”

“…A handful of studies have reported mild to moderate alterations in chromatin organization in the sperm from various patient cohorts including: men with reduced/altered semen parameters, carriers of structural chromosome aberrations, increased sperm aneuploidy and DNA fragmentation etc. [15,19,45,56,57,58,59]. However, these studies are restricted to small numbers of patients and cells.…”

Globozoospermia syndrome: An update

“…As sufferers are routinely screened for DPY19L2 deletion in this centre and according to a recent report by Ghazavi et al (), it has been suggested that embryos derived from couples in consanguineous marriages with globozoospermia should be screened for gender or DPY19L2 deletion in order to decrease the occurrence of globozoospermia in future progeny. Recent findings have clarified that DPY19L2 might have a key role in nuclear chromatin organisation in the sperm nucleus via its interaction with the nuclear lamina (NL) (Abdelhedi et al, ). The impact of the NL and its associated proteins during human spermiogenesis has been emphasised (Paci et al, ).…”