Blood plasma trimethylamine N-oxide and related metabolites and asthenozoospermia odds: a hospital-based matched case-control study in China.

study questionAre blood plasma trimethylamine N-oxide (TMAO) and related metabolites linked to the odds of asthenozoospermia? SUMMARY ANSWER: Increased blood plasma TMAO levels were positively associated with the odds of asthenozoospermia, while elevated levels of choline and L-carnitine were related to reduced asthenozoospermia odds, implying that TMAO and its related metabolites might play an important role in the development of asthenozoospermia. WHAT IS KNOWN ALREADY: Sperm motility and concentration are profoundly impaired by excessive reactive oxygen species (ROS). A positive correlation has been established between ROS levels and TMAO, which is regarded as a key regulatory factor for initiating mitochondrial ROS production. However, the precise interplay between TMAO and its metabolites and sperm quality remains inconclusive and insufficient. STUDY DESIGN SIZE DURATION: This case-control study was conducted from June 2020 to December 2020. A total of 314 pairs of asthenozoospermia cases and normozoospermia controls, matched based on age, BMI, and smoking status, were included. PARTICIPANTS/MATERIALS SETTING

methodsBlood plasma levels of TMAO and five related metabolites, such as choline, betaine, L-carnitine, methionine, and dimethylglycine, were measured using a liquid chromatography system coupled with tandem mass spectrometry. Multivariable conditional logistic regression models were used to estimate the odds ratios (ORs) and corresponding 95% CIs. MAIN RESULTS AND THE ROLE OF CHANCE: Compared with the lowest quartile, a significant association was observed between blood plasma TMAO level (OR = 1.80, 95% CI = 1.16-2.81) and the odds of asthenozoospermia for the highest quartile. In contrast, choline (OR = 0.59, 95% CI = 0.37-0.92) and L-carnitine (OR = 0.58, 95% CI = 0.37-0.90) levels were significant inversely associated with the odds of asthenozoospermia. Additionally, for each per SD change, significant dose-response relationships were noted with increased odds of asthenozoospermia linked to elevated TMAO (OR = 1.31, 95% CI = 1.12-1.55), as well as L-carnitine (OR = 0.79, 95% CI = 0.67-0.93) and total methyl donors exposure (OR = 0.82, 95% CI = 0.70-0.96) levels. LIMITATIONS REASONS FOR CAUTION: We cannot infer causality from this study due to the case-control study. Since the current study was conducted on a population of Chinese men, the extrapolated results may not accurately reflect other regions or populations. As blood plasma TMAO and its metabolites were measured at a single time point and may not accurately represent long-term concentrations, the enduring effects on sperm quality may not be fully captured. Another limitation of the current study lies in its relatively modest sample size, which may have been insufficient to reach statistical power in subgroup analyses. WIDER IMPLICATIONS OF THE

findingsThis study indicated that elevated blood plasma TMAO levels were associated with increased odds of asthenozoospermia, while higher concentrations of choline and L-carnitine decreased asthenozoospermia odds. Our results provide novel evidence that TMAO and its metabolites may serve as potential biomarkers for asthenozoospermia. STUDY FUNDING/COMPETING INTERESTS: No funding was received for this study. All authors have no conflict of interest to declare. TRIAL REGISTRATION NUMBER: N/A.