• PMID: 28882431
• Gene Name: DPY19L2
• Condition: Globozoospermia
• Association: Associated
• Sex: Male
• Infertility type: Male infertility

Abnormal retention of nuclear lamina and disorganization of chromatin-related proteins in spermatozoa from DPY19L2-deleted globozoospermic patients

Paci M, Elkhatib R, Longepied G, Hennebicq S, Bessonat J, Courbière B, Bourgeois P, Levy N, Mitchell MJ, Metzler-Guillemain C.

The aim of this study was to characterize the nuclear lamina (NL) and lamin chromatin-partners in spermatozoa from four DPY19L2-deleted globozoospermic patients. We tested for spermatid transcripts encoding lamins and their chromatin-partners emerin, LAP2α, BAF and BAF-L, by reverse transcriptase-PCR using spermatozoa RNA. We also determined the localization of lamin B1, BAF and BAF-L by immunofluorescent analysis of spermatozoa from all patients. In RNA from globozoospermic and control spermatozoa we detected transcripts encoding lamin B1, lamin B3, emerin, LAP2α and BAF-L, but not A-type lamins. In contrast, BAF transcripts were detected in globozoospermic but not control spermatozoa. The NL was immature in human globozoospermic spermatozoa: lamin B1 signal was detected in the nuclei of globozoospermic spermatozoa in significantly higher proportions than the control (P < 0.05; 56-91% versus 40%) and was predominantly observed at the whole nuclear periphery, not polarized as in control spermatozoa. Conversely, BAF and BAF-L were detected in control, but not globozoospermic spermatozoa. Our results strongly emphasize the importance of the NL and associated proteins during human spermiogenesis. In globozoospermia, the lack of maturation of the NL, and the modifications in expression and location of chromatin-partners, could explain the chromatin defects observed in this rare phenotype. CI - Copyright © 2017 Reproductive Healthcare Ltd. Published by Elsevier Ltd. All rights reserved. FAU - Paci, Marine AU - Paci M AD - Aix Marseille University, Inserm, GMGF, 13385 Marseille, Cedex 5, France; APHM Hôpital La Conception, Pôle Femmes-Parents-Enfants, Centre Clinico-Biologique d'Assistance Médicale à la Procréation-CECOS, 13385 Marseille, Cedex 5, France. FAU - Elkhatib, Razan AU - Elkhatib R AD - Aix Marseille University, Inserm, GMGF, 13385 Marseille, Cedex 5, France. FAU - Longepied, Guy AU - Longepied G AD - Aix Marseille University, Inserm, GMGF, 13385 Marseille, Cedex 5, France. FAU - Hennebicq, Sylviane AU - Hennebicq S AD - CHU de Grenoble, Centre d'Assistance Médicale à la Procréation-CECOS, BP217, Grenoble Cedex 9, France. FAU - Bessonat, Julien AU - Bessonat J AD - CHU de Grenoble, Centre d'Assistance Médicale à la Procréation-CECOS, BP217, Grenoble Cedex 9, France. FAU - Courbière, Blandine AU - Courbière B AD - APHM Hôpital La Conception, Pôle Femmes-Parents-Enfants, Centre Clinico-Biologique d'Assistance Médicale à la Procréation-CECOS, 13385 Marseille, Cedex 5, France. FAU - Bourgeois, Patrice AU - Bourgeois P AD - Aix Marseille University, Inserm, GMGF, 13385 Marseille, Cedex 5, France. FAU - Levy, Nicolas AU - Levy N AD - Aix Marseille University, Inserm, GMGF, 13385 Marseille, Cedex 5, France. FAU - Mitchell, Michael J AU - Mitchell MJ AD - Aix Marseille University, Inserm, GMGF, 13385 Marseille, Cedex 5, France.