Molecular Analysis of <i>DPY19L2</i>, <i>PICK1</i> and <i>SPATA16</i> in Italian Unrelated Globozoospermic Men
Fabiana Faja,
Francesco Pallotti,
Francesco Cargnelutti,
Giulia Senofonte,
Tania Carlini,
Andrea Lenzi,
Francesco Lombardo,
Donatella Paoli
Affiliations
Fabiana Faja
Laboratory of Seminology—“Loredana Gandini” Sperm Bank, Department of Experimental Medicine, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Francesco Pallotti
Laboratory of Seminology—“Loredana Gandini” Sperm Bank, Department of Experimental Medicine, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Francesco Cargnelutti
Laboratory of Seminology—“Loredana Gandini” Sperm Bank, Department of Experimental Medicine, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Giulia Senofonte
Laboratory of Seminology—“Loredana Gandini” Sperm Bank, Department of Experimental Medicine, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Tania Carlini
Laboratory of Seminology—“Loredana Gandini” Sperm Bank, Department of Experimental Medicine, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Andrea Lenzi
Laboratory of Seminology—“Loredana Gandini” Sperm Bank, Department of Experimental Medicine, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Francesco Lombardo
Laboratory of Seminology—“Loredana Gandini” Sperm Bank, Department of Experimental Medicine, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
Donatella Paoli
Laboratory of Seminology—“Loredana Gandini” Sperm Bank, Department of Experimental Medicine, “Sapienza” University of Rome, Viale del Policlinico 155, 00161 Rome, Italy
This study aims to evaluate genetic contribution and sperm DNA fragmentation (SDF) in a cohort of 18 unrelated globozoospermic Italian men (Group G). Semen samples were assessed according to the WHO 2010 Laboratory Manual and compared with 31 fertile controls. We focused our genetic analysis on the exons of the main globozoospermia-associated genes, performing qualitative PCR to assess deletion of DPY19L2 and sequencing to detect mutations of SPATA16 and PICK1. SDF was evaluated using the TUNEL assay. In Group G, 10 patients had a complete form of globozoospermia, whereas 8 patients had a partial form. Molecular analysis revealed deletion of DPY19L2 in six of the patients, all of them with complete globozoospermia, while no mutations were found in the examined exons of PICK1 and SPATA16. TUNEL analysis showed a higher SDF% in Group G. Our findings confirm DPY19L2 defects as the most frequent genetic alteration in Italian patients contributing to globozoospermic phenotypes. Furthermore, spermatozoa with acrosomal defects could also display high levels of SDF as a possible consequence of abnormally remodeled chromatin. The possible effect on offspring of chromatin structure abnormalities and altered DNA integrity should be carefully evaluated by clinicians, especially regarding the feasibility and safety of artificial reproductive techniques, which represent the only treatment that allows these patients to conceive.
