Mediation of the relationship between phthalate exposure and semen quality by oxidative stress among 1034 reproductive-aged Chinese men.

Environ Res

Key Laboratory of Environment and Health, Ministry of Education & Ministry of Environmental Protection, State Key Laboratory of Environmental Health (incubating), Department of Occupational and Environmental Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, PR China; Departments of Nutrition and Epidemiology, Harvard TH Chan School of Public Health, Boston, MA, USA. Electronic address:

Published: December 2019

Background: Emerging evidence from animals indicates that oxidative stress plays a crucial role in the effects of phthalate exposure on male reproductive dysfunctions, which has never been thoroughly explored in humans.

Objective: To explore the potential mediating role of oxidative stress in the association of phthalate exposure with semen quality among 1034 Chinese men.

Method: Repeated urine samples gathered from the male partners of sub-fertile couples were analyzed for 3 oxidative stress markers [8-hydroxy-2-deoxyguanosine (8-OHdG), 8-iso-prostaglandin F (8-isoPGF) and 4-hydroxy-2-nonenal-mercapturic acid (HNE-MA)], using a liquid chromatography-tandem mass spectrometry. Multivariate regression models were constructed to evaluate the associations of urinary oxidative stress markers with urinary phthalate metabolites and semen quality. We also explored the potential mediation effects by oxidative stress markers.

Results: Significantly positive dose-dependent relationships were observed between each individual phthalate metabolite and all analyzed oxidative stress markers (all p for trend<0.05), except for monoethyl phthalate (MEP) in relation to HNE-MA. Additionally, significantly or suggestively inverse dose-dependent relationships were exhibited between urinary 8-isoPGF and sperm concentration (p for trend = 0.05), and between urinary 8-OHdG and percent of normal sperm morphology (p for trend = 0.01). Mediation analysis showed that urinary 8-isoPGF suggestively mediated 12% of the inverse association between monobutyl phthalate (MBP) and sperm concentration, and that urinary 8-OHdG suggestively mediated 32% of the inverse association of MEP with percent of normal sperm morphology (both p < 0.10).

Conclusions: Although further investigations are required, our results suggest that oxidative stress may play a mediating role in the effects of phthalate exposure on impaired semen quality.

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http://dx.doi.org/10.1016/j.envres.2019.108778DOI Listing

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