Relevance of PUFA-derived metabolites in seminal plasma to male infertility

Xiangfeng Chen; Bin Wu; XiaoRong Shen; Xin Wang; Ping Ping; Maohua Miao; Ningning Liang; Huiyong Yin; Huijuan Shi; Jun Qian; Tiancheng Zhang

doi:10.3389/fendo.2023.1138984

Relevance of PUFA-derived metabolites in seminal plasma to male infertility

Front Endocrinol (Lausanne). 2023 May 22:14:1138984. doi: 10.3389/fendo.2023.1138984. eCollection 2023.

Authors

Xiangfeng Chen¹, Bin Wu², XiaoRong Shen², Xin Wang², Ping Ping¹, Maohua Miao², Ningning Liang^{3

4}, Huiyong Yin^{3

4

5}, Huijuan Shi², Jun Qian², Tiancheng Zhang²

Affiliations

¹ Shanghai Human Sperm Bank, Shanghai Key Laboratory for Assisted Reproduction and Reproductive Genetics, Center for Reproductive Medicine, Ren Ji Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² National Health Commission of the PRC (NHC), Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, Fudan University, Shanghai, China.
³ CAS Key Laboratory of Nutrition, Metabolism, and Food Safety, Shanghai Institute of Nutrition and Health, Chinese Academy of Sciences (CAS), Shanghai, China.
⁴ School of Life Science and Technology, ShanghaiTech University, Shanghai, China.
⁵ Department of Biomedical Sciences, City University of Hong Kong, Hong Kong, China.

Abstract

Aim: This study aims to investigate the biological effects of polyunsaturated fatty acid (PUFA)-derived metabolites in seminal plasma on male fertility and to evaluate the potential of PUFA as a biomarker for normozoospermic male infertility.

Methods: From September 2011 to April 2012, We collected semen samples from 564 men aged 18 to 50 years old (mean=32.28 years old)ch., residing in the Sandu County, Guizhou Province, China. The donors included 376 men with normozoospermia (fertile: n=267; infertile: n=109) and 188 men with oligoasthenozoospermia (fertile: n=121; infertile: n=67). The samples thus obtained were then analyzed by liquid chromatography-mass spectrometry (LC-MS) to detect the levels of PUFA-derived metabolites in April 2013. Data were analyzed from December 1, 2020, to May 15, 2022.

Results: Our analysis of propensity score-matched cohorts revealed that the concentrations of 9/26 and 7/26 metabolites differed significantly between fertile and infertile men with normozoospermia and oligoasthenozoospermia, respectively (FDR < 0.05). In men with normozoospermia, higher levels of 7(R)-MaR1 (HR: 0.4 (95% CI [0.24, 0.64]) and 11,12-DHET (0.36 (95% CI [0.21, 0.58]) were significantly associated with a decreased risk of infertility, while higher levels of 17(S)-HDHA (HR: 2.32 (95% CI [1.44, 3.79]), LXA5 (HR: 8.38 (95% CI [4.81, 15.24]), 15d-PGJ2 (HR: 1.71 (95% CI [1.06, 2.76]), and PGJ2 (HR: 2.28 (95% CI [1.42, 3.7]) correlated with an increased risk of infertility. Our ROC model using the differentially expressed metabolites showed the value of the area under the curve to be 0.744.

Conclusion: The PUFA-derived metabolites 7(R)-MaR1, 11,12-DHET, 17(S)-HDHA, LXA5, and PGJ2 might be considered as potential diagnostic biomarkers of infertility in normozoospermic men.

Keywords: male infertility; metabolic profile; normozoospermia; polyunsaturated fatty acids; seminal plasma; sperm.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Adolescent
Adult
Fatty Acids, Unsaturated / metabolism
Humans
Infertility, Male* / metabolism
Male
Middle Aged
Semen* / metabolism
Sperm Count
Sperm Motility
Young Adult

Substances

Fatty Acids, Unsaturated

Grants and funding

This study was supported by grants from the Ministry of Science and Technology of China (2018YFC1005001 and 2014CB943104), the National Natural Science Foundation of China (32070849,32030053, 32150710522),Youth Program of Shanghai Municipal Health Commission (20204Y0276), The Foundation of Science and Technology Commission of Shanghai Municipality(17JC1420103), Basic Research Program of China (973 Program, 2012CBA01306, 2009CB941703).