Polymorphic Rearrangements of Human Chromosome 9 and Male Infertility: New Evidence and Impact on Spermatogenesis

Abstract

Chromosomal polymorphisms are structural variations in chromosomes that define the genomic variance of a species. These alterations are recurrent in the general population, and some of them appear to be more recurrent in the infertile population. Human chromosome 9 is highly heteromorphic, and how its rearrangement affects male fertility remains to be fully investigated. In this study, we aimed to investigate the association between the polymorphic rearrangements of chromosome 9 and male infertility via an Italian cohort of male infertile patients. Cytogenetic analysis was carried out, along with Y microdeletion screening, semen analysis, fluorescence in situ hybridization, and TUNEL assays using spermatic cells. Chromosome 9 rearrangements were observed in six patients: three of them showed a pericentric inversion, while the others showed a polymorphic heterochromatin variant 9qh. Of these, four patients exhibited oligozoospermia associated with teratozoospermia, along with a percentage of aneuploidy in the sperm of above 9%, in particular, an increase in XY disomy. Additionally, high values for sperm DNA fragmentation (≥30%) were observed in two patients. None of them had microdeletions to the AZF loci on chromosome Y. Our results suggest that polymorphic rearrangements of chromosome 9 might be associated with abnormalities in sperm quality due to incorrect spermatogenesis regulation.

Exploring the impact of pericentric inversion of chromosome 9 on fertility in sperm donors

“…In addition, a recent study by Mottola et al . 13 suggested a link between polymorphic rearrangements with abnormalities in sperm quality, including increased aneuploidy rates and high DFI. In contrast, in this study, the control group outperformed inv(9) carriers only in ROS levels.…”

“…Consequently, the biological and clinical significance of inv(9) remains controversial in the literature. 12 13 14 There is a lack of research on recruiting sperm donors who meet the eligibility criteria for sperm banks but carry the inv(9) variant (referred to as inv[9]-eligible donors). It is uncertain if using their sperm for AID poses clinical risks.…”

“…Third, the analysis of 24 chromosomes was performed on sperm from inv(9)-eligible donors. Previous studies have reported an increased incidence of aneuploidy in spermatozoa of men with inv(9) 4 13 15 and the potential influence of inter-chromosomal effects (ICE). 16 Fourth, we evaluated the semen samples from inv(9)-eligible donors for sperm morphology and functional parameters.…”

Environmental and Genetic Traffic in the Journey from Sperm to Offspring

“…While some ROS are necessary for optimal sperm function, excessive amounts can damage sperm via lipid peroxidation, DNA, and chromatin integrity, leading to fertilization failure and pregnancy loss [88]. Spermatozoa themselves produce limited ROS, as they lose most of their cytoplasm during development; however, external factors such as toxins can increase seminal ROS levels [89]. Lifestyle factors like smoking, obesity, and stress contribute to OS, adversely affecting male fertility [8,90,91].…”

“…Additionally, toxic substances like sulfur mustard cause DNA alkylation and ROS production [96]. Damaged sperm DNA can reduce sperm count due to apoptosis and is linked to recurrent pregnancy loss because of genetic defects affecting the embryo [89,97,98].…”