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Dietary exposure to di-isobutyl phthalate increases urinary 5-methyl-2'-deoxycytidine level and affects reproductive function in adult male mice
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China; University of Chinese Academy of Sciences, Beijing, China.
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
Örebro University, School of Science and Technology. (Man-Technology-Environment Research Centre (MTM))ORCID iD: 0000-0001-6800-5658
Key Laboratory of Animal Ecology and Conservation Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing, China.
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2017 (English)In: Journal of Environmental Sciences(China), ISSN 1001-0742, E-ISSN 1878-7320, Vol. 61, 14-23 p.Article in journal (Refereed) Published
Abstract [en]

Phthalates are a large family of ubiquitous environmental pollutants suspected of being endocrine disruptors. Epidemiological studies have associated phthalate metabolites with decreased reproductive parameters and linked phthalate exposure with the level of urinary 5-methyl-2'-deoxycytidine (5mdC, a product of methylated DNA). In this study, adult male mice were exposed to 450mg di-isobutyl phthalate (DiBP)/(kg·day) via dietary exposure for 28days. Mono-isobutyl phthalate (MiBP, the urinary metabolite) and reproductive function parameters were determined. The levels of 5mdC and 5-hydroxymethyl-2'-deoxycytidine (5hmdC) were measured in urine to evaluate if their contents were also altered by DiBP exposure in this animal model. Results showed that DiBP exposure led to a significant increase in the urinary 5mdC level and significant decreases in sperm concentration and motility in the epididymis, accompanied with reduced testosterone levels and down-regulation of the P450 cholesterol side-chain cleavage enzyme (P450scc) gene in the mice testes. Our findings indicated that exposure to DiBP increased the urinary 5mdC levels, which supported our recent epidemiological study about the associations of urinary 5mdC with phthalate exposure in the male human population. In addition, DiBP exposure impaired male reproductive function, possibly by disturbing testosterone levels; P450scc might be a major steroidogenic enzyme targeted by DiBP or other phthalates.

Place, publisher, year, edition, pages
Elsevier, 2017. Vol. 61, 14-23 p.
Keyword [en]
5-Methyl-2′-deoxycytidine (5mdC), Deoxyribonucleic acid (DNA) methylation, Di-isobutyl phthalate (DiBP), Reproductive function, Testosterone
National Category
Occupational Health and Environmental Health
Identifiers
URN: urn:nbn:se:oru:diva-62949DOI: 10.1016/j.jes.2017.04.036ISI: 000416721600003PubMedID: 29191310Scopus ID: 2-s2.0-85020387739OAI: oai:DiVA.org:oru-62949DiVA: diva2:1163490
Note

Funding Agencies:

National Basic Research Program of China  2013CB945004 

National Natural Science Foundation of China  21477127 

Available from: 2017-12-07 Created: 2017-12-07 Last updated: 2018-01-13Bibliographically approved

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Yeung, Leo W. Y.

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