Metabolomics of Human Seminal Fluid Reveals Aging-Related Increase in the Amino Acid Content

Background: Aging is the progressive decline in an organism's structural and functional characteristics. Aging has also been linked to a reduction in male reproductive potential. In contemporary societies where delayed parenthood is prevalent, there is a burgeoning interest in comprehending the age -related decline in male fertility and its implications for offspring. This study delves into investigating the metabolome of human seminal fluid, aiming to unveil potential metabolite biomarkers of male reproductive potential during the aging process, employing a Nuclear Magnetic Resonance (NMR)-based metabolomics approach. Methods: Seminal samples from 31 healthy normozoospermic men (age range from 25 to 50 years old) undergoing fertility treatment were examined. Routine semen analyses were performed on fresh semen samples to determine the sperm parameters according to the World Health Organization guidelines. Seminal fluid was separated from spermatozoa and the metabolic profile was analyzed through H-1 -Nuclear Magnetic Resonance (1H-NMR). The samples were separated into two groups based on age (<35 years and >= 35 years) and multivariate analysis was performed on the quantified metabolites. Results: Employing this NMR-based metabolomics approach, we identified 37 small metabolites across all seminal fluid samples. Partial least squares -discriminant analysis unveiled a clustering trend between age groups. Notably, a significant age -associated increase in the amino acids serine and aspartate was observed. Moreover, a propensity for increased levels of various amino acids in seminal fluid with advancing age was observed. Conversely, seminal levels of malate exhibited a decline in older individuals. Conclusions: Our findings provide compelling evidence of age exerting a discernible influence on the comprehensive seminal metabolome. These results underscore the potential for future omics studies, focusing on unraveling the intricate molecular mechanisms that underlie the age -associated decline in male fertility.