Seminal plasma metabolome in relation to semen quality and urinary phthalate metabolites among Chinese adult men

Yi-Xin Wang; Yan Wu; Heng-Gui Chen; Peng Duan; Liang Wang; He-Qing Shen; Wen-Qing Lu; Bin Sun; Qi Wang; Bo Zhang; Jorge E Chavarro; Jie Zhang; An Pan

doi:10.1016/j.envint.2019.05.043

Seminal plasma metabolome in relation to semen quality and urinary phthalate metabolites among Chinese adult men

Environ Int. 2019 Aug:129:354-363. doi: 10.1016/j.envint.2019.05.043. Epub 2019 May 28.

Authors

Yi-Xin Wang¹, Yan Wu², Heng-Gui Chen³, Peng Duan⁴, Liang Wang⁵, He-Qing Shen², Wen-Qing Lu³, Bin Sun³, Qi Wang⁶, Bo Zhang⁷, Jorge E Chavarro⁸, Jie Zhang⁹, An Pan¹⁰

Affiliations

¹ Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China; Departments of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
² Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China.
³ Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
⁴ Center for Reproductive Medicine, Xiangyang No. 1 People's Hospital, Hubei University of Medicine, Xiangyang, China.
⁵ Departments of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA; Department of Biostatistics and Epidemiology, College of Public Health, East Tennessee State University, Johnson City, TN, USA.
⁶ Department of Pathology, Bengbu Medical College, Anhui, China.
⁷ Departments of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA; Department of Biochemistry, Fukuoka University School of Medicine, Fukuoka, Japan.
⁸ Departments of Nutrition, Harvard TH Chan School of Public Health, Boston, MA, USA.
⁹ Key Lab of Urban Environment and Health, Institute of Urban Environment, Chinese Academy of Sciences, Xiamen, China; School of Public Health, Xiamen University, Xiamen, China. Electronic address: jie.zhang@xmu.edu.cn.
¹⁰ Department of Epidemiology and Biostatistics, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China. Electronic address: panan@hust.edu.cn.

PMID: 31150977
DOI: 10.1016/j.envint.2019.05.043

Abstract

Background: A growing body of evidence has found links between endocrine disruptor phthalates and male reproductive disorders, but the mechanisms underlying these relationships are poorly known. Seminal plasma metabolomes may mediate associations of phthalate exposure with impaired semen quality.

Objective: To identify seminal plasma metabolomes associated with poor semen quality and evaluate their associations with urinary phthalate metabolites among 660 Chinese adult men.

Method: The seminal plasma metabolic profiles were acquired using an untargeted approach based on liquid chromatography-high resolution mass spectrometry. We explored the differences in seminal plasma metabolites between participants with poor and good semen quality and evaluated cross-sectional associations between discriminatory metabolic biomarkers and urinary phthalate metabolites.

Results: Differences between poor and good semen quality groups were observed in relation to 25 seminal plasma metabolites, mostly related to the metabolism of polyunsaturated fatty acids (PUFA) and acylcarnitine (all p < 0.05). After adjusting for various confounders and multiple tests, metabolites were all significantly associated with one or more individual sperm quality parameters (motility, concentration, total count, and morphology) (all p < 0.05). Among identified metabolic biomarkers, seminal plasma L-palmitoylcarnitine, linoelaidyl carnitine, and oleic acid were inversely associated with urinary mono-(2-ethylhexyl) phthalate (MEHP), and seminal plasma L-acetylcarnitine was inversely associated with the proportion of di-(2-ethylhexyl)-phthalate metabolites (DEHP) excreted as MEHP in urine (%MEHP) (all p < 0.05). Mediation analysis revealed that oleic acid and L-acetylcarnitine mediated significant proportions (6.7% and 17%, respectively) of the positive associations between urinary DEHP metabolites and the percentage of spermatozoa with an abnormal head.

Conclusions: Elevated urinary phthalate metabolites may impact semen quality by causing metabolic disorders of seminal plasma PUFAs and acylcarnitine. These pathways warrant further investigation.

Keywords: Phthalates; Reproductive-aged men; Semen quality; Seminal plasma metabolome.

Publication types

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

MeSH terms

Adult
Asian People
Carnitine / analogs & derivatives
Carnitine / urine
Chromatography, Liquid
Cross-Sectional Studies
Diethylhexyl Phthalate / metabolism
Humans
Male
Metabolome*
Phthalic Acids / urine*
Semen / metabolism*
Semen Analysis
Spermatozoa / metabolism
Tandem Mass Spectrometry

Substances

Phthalic Acids
acylcarnitine
phthalic acid
Diethylhexyl Phthalate
Carnitine