Relationship between Semen NAD+ Concentration and Reproductive Aging in Normazoospermia Men: A Cohort Study

Background: The mechanisms of age-dependent reproductive decline in men are largely overlooked. Age-dependent reduction of nicotinamide adenine dinucleotide (NAD+) levels has been reported in multiple somatic and female reproductive tissues, including oocytes and ovarian tissue. However, the relationship between NAD+ levels and male zygote has not been studied yet. In the current study, the association between semen NAD+ levels and paternal age will be investigated. Besides, we will also answer if semen NAD+ levels are related to semen quality. Methods: In this pilot observatory cohort study, semen samples of a total of 51 male subjects who visited a university-affiliated reproductive medical center for preconception consultation (40 years: n=19) were recruited. Anthropometric characteristics were recorded, and semen analysis was performed. Sperm NAD+ levels were evaluated spectrophotometrically. Results: Between the three age groups, there was on significant difference in major parameters of semen quality. Semen NAD+ level was also similar between the three groups (40 years:115.59±16.55 nmol/10 6 sperm). Additionally, linear aggression also revealed no correlation between semen NAD+ concentration and the age of the participants (r 2 =0.018, p=0.35). Noticeably, negative correlation was found between semen NAD+ concentrations and sperm quality parameters, including sperm concentration (r 2 =0.78 p<0.0001), sperm count (r 2 =0.47. p<0.0001.), mobile sperm number (r 2 =33. P<0.0001), and DFI (r 2 =0.35 p<0.0001). As for semen volume and mobility rate, these two parameters were not related to semen NAD+ concentration. Conclusions: Unlike decreased NAD+ levels in aged oocytes and ovarian tissue, semen NAD+ concentration is not age-dependent. Semen NAD+ level negatively correlates with sperm quality, suggesting the unique role of NAD+ in spermatogenesis, which warrants further study and opens opportunities for pharmaceutical interventions of oligospermia.