Serum Metabolomic Profiling Identifies Characterization of Non-Obstructive Azoospermic Men

Abstract

Male infertility is considered a common health problem, and non-obstructive azoospermia with unclear pathogenesis is one of the most challenging tasks for clinicians. The objective of this study was to investigate the differential serum metabolic pattern in non-obstructive azoospermic men and to determine potential biomarkers related to spermatogenic dysfunction. Serum samples from patients with non-obstructive azoospermia (n = 22) and healthy controls (n = 31) were examined using high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS/MS). Serum metabolomic profiling could differentiate non-obstructive azoospermic patients from healthy control subjects. A total of 24 metabolites were screened and identified as potential markers, many of which are involved in energy production, oxidative stress and cell apoptosis in spermatogenesis. Moreover, the results showed that various metabolic pathways, including d-glutamine and d-glutamate metabolism, taurine and hypotaurine metabolism, pyruvate metabolism, the citrate cycle and alanine, aspartate and glutamate metabolism, were disrupted in patients with non-obstructive azoospermia. Our results indicated that the serum metabolic disorders may contribute to the etiology of non-obstructive azoospermia. This study suggested that serum metabolomics could identify unique metabolic patterns of non-obstructive azoospermia and provide novel insights into the pathogenesis underlying male infertility.

Testicular tissue oxidative stress in azoospermic patients: Effect of cryopreservation

“…Spermatozoa can be affected by ROS hazardously through its damaging effects on sperm membrane lipids, mitochondrial function and DNA integrity. Infertile men with defective spermatogenesis, as in NOA, were found to have inherent metabolic stresses and higher levels of testicular oxidative stress (Rahbar et al., 2017; Zhang et al., 2017). Induction of further OS for testicular spermatozoa could theoretically affect the outcomes of ICSI using these spermatozoa (Ghaleno et al., 2014).…”

Assessment of Blood Plasma Free-amino Acid Levels in Infertile Men

“…Therefore, FSH levels and sperm count do not influence the balance of the AA concentrations and may not be correlated to spermatogenic function in infertile men. In a previous study, investigating serum samples from non-obstructive azoospermic men, various metabolic pathways, but not those associated with AAs, were shown to be disrupted, suggesting the involvement of serum metabolic disorders in the pathogenesis of male infertility (19).…”

“…Considering the important roles of AAs in a wide variety of pathophysiological events, we evaluated our findings, focusing only on men with either normospermia or oligozoospermia, and found significantly lower levels of alanine and tryptophan in men with lower motility rates, and lower levels of aspartic acid and glutamic acid in men with higher abnormal morphology rates. To date, a number of studies have reported the effects of these four AAs on sperm function (8,11,14,15,(19)(20)(21)(22)(23)(24). For example, in vitro motility, longevity, and in vivo fertility were enhanced in bull spermatozoa by tryptophan supplementation (11), while oral administration of aspartic acid resulted in the improvement of sperm quality and fertility using a rooster model (20).…”

Sperm selection in IVF: the long and winding road from bench to bedside

“…A differentiated serum metabolomic profiling has also been described in non-obstructive azoospermic men in comparison to healthy control subjects. Results identified 24 metabolites involved in crucial steps for spermatogenesis, such as energy production, oxidative stress and cell apoptosis ( Zhang et al ., 2017 ).…”