Investigation on the origin of sperm morphological defects: oxidative attacks, chromatin immaturity, and DNA fragmentation.Environ Sci Pollut Res Int. 2018 May; 25(14):13775-13786.ES
DNA fragmentation can be deleterious on spermatozoon morphology but the pathogenesis of teratozoospermia associated with DNA breaks is not fully understood, even if oxidative attacks and defects in chromatin maturation are hypothesized. Therefore, this study is one of the first to clarify on the underlying hypothesizes behind such observations. The objectives of our study were to assess the role of oxidative attacks in DNA damage pathogenesis in ejaculated spermatozoa from patients with isolated teratozoospermia. We aimed to assess the correlation of DNA breaks with morphologically abnormal spermatozoa, as well as ROS level and impairment chromatin condensation. A total of 90 patients were divided into two groups, men with isolated teratozoospermia (n = 60) and men with normal semen parameters (n = 30) as controls. DNA fragmentation was evaluated by TUNEL assay; chromatin immaturity was studied using acridine orange and toluidine blue staining. We evaluated the ability of spermatozoa to produce reactive oxygen species with nitro blue tetrazolium staining. Patient with teratozoospermia when compared to fertile men showed significantly higher rates of semen ROS production, sperm hypocondensated chromatin, denaturated DNA, and fragmented DNA. All these parameters were positively correlated with abnormal sperm morphology. The studied DNA integrity markers were also correlated with ROS production. Fragmented DNA is the main pathway leading to morphology defects in the sperm. In fact, impaired chromatin compaction may induce DNA breaks and free radicals, which can break the DNA backbone indirectly, by reducing protamination and disulphide bond formation, as oxidative attack appears to be the major cause of poor semen morphology.