Abstract
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.
Highlights
Infertility, defined by the World Health Organization (WHO) as the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse, is a major concern in public health
To further assess a putative correlation with impaired chromatin integrity, we evaluated sperm DNA fragmentation (SDF) in acrosomeless spermatozoa in our cohort of globozoospermic patients and compared it to fertile controls
We focused our analysis on DPY19L2 deletion and sequencing of SPATA16 and PICK1, assessing putative genetic variants of the mainly altered exons as reported in literature
Summary
Infertility, defined by the World Health Organization (WHO) as the failure to achieve a pregnancy after 12 months or more of regular unprotected sexual intercourse, is a major concern in public health. A rare (incidence < 0.1%) genetic cause of infertility is globozoospermia. The peculiar appearance of globozoospermic ejaculates is that of a monomorphic teratozoospermia, characterized by round-headed spermatozoa lacking an acrosome [3]. The absence of an acrosome makes spermatozoa unable to interact with the zona pellucida, leading to primary infertility [4]. Even though a high incidence of fertilization failure is described [5], intracytoplasmic sperm injection (ICSI) is considered the only treatment to achieve conception. Artificial oocyte activation (AOA) with calcium ionophore may improve ICSI outcome, but fertilization rates remain low [6]
Sign-in/Register to view highlights & summary 
Published Version (
Free)
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call