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Sci Rep. 2014 Sep 22;4:6434. doi: 10.1038/srep06434.

Di-(2-ethylhexyl) phthalate inhibits DNA replication leading to hyperPARylation, SIRT1 attenuation, and mitochondrial dysfunction in the testis.

Author information

1
1] School of Public Health, Fudan University, Shanghai, 200032, China [2] Shanghai Entry-Exit Inspection and Quarantine Bureau, Shanghai, 200135, China [3].
2
1] Laboratory of Molecular Gerontology, National Institute on Ageing, National Institutes of Health, Baltimore, MD USA [2] School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Shatin, New Territories, Hong Kong [3].
3
Laboratory of Molecular Gerontology, National Institute on Ageing, National Institutes of Health, Baltimore, MD USA.
4
Shanghai Stomatological Disease Centre. Shanghai, 200001, PR China.
5
Shanghai Entry-Exit Inspection and Quarantine Bureau, Shanghai, 200135, China.
6
School of Biomedical Sciences, Faculty of Medicine, The Chinese University of Hong Kong, Hong Kong, Shatin, New Territories, Hong Kong.
7
School of Public Health, Fudan University, Shanghai, 200032, China.

Abstract

Di-(2-ethylhexyl)-phthalate (DEHP) is a ubiquitously used endocrine disruptor.There is widespread exposure to DEHP in the general population which has raised substantial public concern due to its potential detrimental health effects. It is particularly pertinent to investigate the molecular mechanisms of its testicular toxicity which are largely unknown. By feeding male rats DEHP for 2 weeks, rat spermatogenesis became disrupted, resulting in a decreased number of spermatocytes and spermatids. Since rapidly dividing tissues appeared to be particularly vulnerable to DEHP toxicity we investigated the effect of DEHP on DNA replication. Intriguingly, DEHP appeared to inhibit DNA replication as evidenced by results of fiber tract analysis. This led to induction of the mitochondrial apoptotic pathways and increased ROS production. Furthermore, the toxicity of DEHP led to respiratory chain defects and attenuation of ATP level probably brought about by hyperPARylation and undermined SIRT1 activity. Our findings reveal a previously unknown mitochondrial dysfunction in DEHP-induced testicular toxicity and highlight the importance of SIRT1 in male reproduction.

PMID:
25242624
PMCID:
PMC4170195
DOI:
10.1038/srep06434
[Indexed for MEDLINE]
Free PMC Article

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