Novel association between sperm deformity index and oxidative stress-induced DNA damage in infertile male patients

Aim:To investigate the impact of abnormal sperm morphology using the sperm deformity index (SDI) on reactive oxygen species (ROS) production and its correlation with sperm DNA damage.Methods:Semen samples were collected from men undergoing infertility screening (n=7) and healthy donors (n=6).Mature spermatozoa were isolated and incubated with 5 mmol/L β-nicotinamide adenine dinucleotide phosphate (NADPH) for up to 24 h to induce ROS.Sperm morphology was evaluated using strict Tygerberg's criteria and the SDI.ROS levels and DNA damage were assessed using chemiluminescence and terminal deoxynucleotidyl transferase-mediated fluorescein- dUTP nick end labeling (TUNEL) assays,respectively.Results:SDI values (median [interquartiles]) were higher in patients than donors (2 [1.8,2.1] vs.1.53 [1.52,1.58],P=0.008).Aliquots treated with NADPH showed higher ROS levels (1.22 [0.30,1.87] vs.0.39 [0.10,0.57],P=0.03) and higher incidence of DNA damage than those not treated (10 [4.69,24.85] vs.3.85 [2.58,5.10],P=0.008).Higher DNA damage was also seen following 24 h of incubation in patients compared to donors.SDI correlated with the percentage increase in sperm DNA damage following incubation for 24 h in samples treated with NADPH (r=0.7,P=0.008) and controls (r=0.58,P=0.04). Conclusion:SDI may be a useful tool in identifying potential infertile males with abnormal prevalence of oxidative stress (OS)-induced DNA damage.NADPH plays a role in ROS-mediated sperm DNA damage,which appears to be more evident in infertile patients with semen samples containing a high incidence of morphologically abnormal spermatozoa.

Assessing human sperm morphology： top models, underdogs or biometrics？

The assessment of the percentage of spermatozoa having an ＇ideal＇ morphology using so-called strict method is the method recommended in the latest edition of the World Health Organization （WHO） laboratory manual for semen analysis. This recommendation is a result of the statistical association between ＇ideal＇ sperm morphology and fertility, and of the current general belief that sperm morphology assessment should be used primarily as a fertility tool. The notion of an ＇ideal＇ sperm morphology has persisted despite the very low percentage of such spermatozoa in the semen of fertile men, a subject of intense controversy. The detailed categorization of each abnormal spermatozoon has thus, for a long time, been considered optional and partially redundant, an idea which is reflected in the earlier editions of the WHO manual. However, several recent studies have shown the importance of carefully assessing abnormal sperm morphology for use in the diagnosis ＆infertility, to determine fertility prognosis, and for basic or public health studies. One approach, which combines videomicroscopy and computer vision, and is the only approach able to assess the continuum of sperm biometrics, has been used successfully in several recent clinical, basic and toxicology studies. In summary, the visual assessment of detailed sperm morphology--including the categorization of anomalies allowing arithmetically derived indices of teratozoospermia--and the more modern computer-based approaches, although often considered to be redundant, are in fact complementary. The choice of the most appropriate method depends on the field of investigation （clinical, research, toxicology） and the problem being addressed. Each approach has advantages as well as certain limitations, which will be discussed briefly herein.

Dependence of sperm structural and functional integrity on testicular calcineurin isoform PPP3R2 expression

After leaving the testis,mammalian sperm undergo a sequential maturation process in the epididymis followed by capacitation during their movement through the female reproductive tract.These phenotypic changes are associated with modification of protein phosphorylation and membrane remodeling,which is requisite for sperm to acquire forward motility and induce fertilization.However,the molecular mechanisms underlying sperm maturation and capacitation are still not fully understood.Herein,we show that PPP3R2,a testis-specific regulatory subunit of protein phosphatase 3(an isoform of calcineurin in the testis),is essential for sperm maturation and capacitation.Knockout of Ppp3r2 in mice leads to male sterility due to sperm motility impairment and morphological defects.One very noteworthy change includes increases in sperm membrane stiffness.Moreover,PPP3R2 regulates sperm maturation and capacitation via(i)modulation of membrane diffusion barrier function at the annulus and(ii)facilitation of cholesterol efflux during sperm capacitation.Taken together,PPP3R2 plays a critical role in modulating cholesterol efflux and mediating the dynamic control of membrane remodeling during sperm maturation and capacitation.