Xing Ze, Xie Meng-Meng, Wang Hui-Han, Cui Qi, Wang Xiao-Bin
Center of Reproductive Medicine, Shengjing Hospital of China Medical University, Shenyang, P.R. China.
Department of Obstetrics and Gynecology, Shengjing Hospital of China Medical University, Shenyang, P.R. China.
Hum Reprod Open. 2025 Aug 18;2025(3):hoaf045. doi: 10.1093/hropen/hoaf045. eCollection 2025.
Are blood plasma trimethylamine N-oxide (TMAO) and related metabolites linked to the odds of asthenozoospermia?
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.
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.
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 METHODS: Blood 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.
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.
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.
This 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.
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血浆三甲胺N-氧化物（TMAO）及相关代谢产物与弱精子症的发生几率是否有关？
血浆TMAO水平升高与弱精子症的发生几率呈正相关，而胆碱和左旋肉碱水平升高与弱精子症发生几率降低有关，这意味着TMAO及其相关代谢产物可能在弱精子症的发生发展中起重要作用。
过量的活性氧（ROS）会严重损害精子活力和浓度。ROS水平与TMAO之间已建立正相关，TMAO被认为是启动线粒体ROS产生的关键调节因子。然而，TMAO及其代谢产物与精子质量之间的确切相互作用仍无定论且证据不足。
研究设计、规模、持续时间：本病例对照研究于2020年6月至2020年12月进行。共纳入314对弱精子症病例和正常精子症对照，根据年龄、BMI和吸烟状况进行匹配。
研究对象/材料、研究环境、研究方法：采用液相色谱-串联质谱联用系统测量血浆中TMAO和五种相关代谢产物，如胆碱、甜菜碱、左旋肉碱、蛋氨酸和二甲基甘氨酸的水平。使用多变量条件逻辑回归模型估计比值比（OR）和相应的95%置信区间（CI）。
与最低四分位数相比，血浆TMAO水平处于最高四分位数时与弱精子症发生几率之间存在显著关联（OR = 1.80，95%CI = 1.16 - 2.81）。相比之下，胆碱（OR = 0.59，95%CI = 0.37 - 0.92）和左旋肉碱（OR = 0.58，95%CI = 0.37 - 0.90）水平与弱精子症发生几率呈显著负相关。此外，对于每标准差的变化，TMAO水平升高（OR = 1.31，95%CI = 1.12 - 1.55）、左旋肉碱（OR = 0.79，95%CI = 0.67 - 0.93）以及总甲基供体暴露水平（OR = 0.82，95%CI = 0.70 - 0.96）与弱精子症发生几率增加之间均存在显著的剂量反应关系。
局限性、谨慎原因：由于本研究为病例对照研究，我们无法从中推断因果关系。由于本研究是在中国男性人群中进行的，外推结果可能无法准确反映其他地区或人群的情况。由于血浆TMAO及其代谢产物是在单一时间点测量的，可能无法准确代表长期浓度，因此对精子质量的持久影响可能未被完全捕捉。本研究的另一个局限性在于其样本量相对较小，可能不足以在亚组分析中达到统计学效力。
本研究表明，血浆TMAO水平升高与弱精子症发生几率增加有关，而较高浓度的胆碱和左旋肉碱可降低弱精子症发生几率。我们的结果提供了新的证据，表明TMAO及其代谢产物可能作为弱精子症的潜在生物标志物。
研究资金/利益冲突：本研究未获得资金支持。所有作者均声明无利益冲突。
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