Di-(2-ethylhexyl) phthalate inhibits DNA replication leading to hyperPARylation, SIRT1 attenuation, and mitochondrial dysfunction in the testis
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Di-(2-ethylhexyl) phthalate inhibits DNA replication leading to hyperPARylation, SIRT1 attenuation, and mitochondrial dysfunction in the testis. / Li, Xiaolin; Fang, Evandro Fei; Scheibye-Knudsen, Morten; Cui, Honghua; Qiu, Lu; Li, Jian; He, Yuping; Huang, Jing; Bohr, Vilhelm A.; Ng, Tzi Bun; Guo, Hongwei.
In: Scientific Reports, Vol. 4, 6434, 2014.Research output: Contribution to journal › Journal article › Research › peer-review
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T1 - Di-(2-ethylhexyl) phthalate inhibits DNA replication leading to hyperPARylation, SIRT1 attenuation, and mitochondrial dysfunction in the testis
AU - Li, Xiaolin
AU - Fang, Evandro Fei
AU - Scheibye-Knudsen, Morten
AU - Cui, Honghua
AU - Qiu, Lu
AU - Li, Jian
AU - He, Yuping
AU - Huang, Jing
AU - Bohr, Vilhelm A.
AU - Ng, Tzi Bun
AU - Guo, Hongwei
PY - 2014
Y1 - 2014
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=84923304409&partnerID=8YFLogxK
U2 - 10.1038/srep06434
DO - 10.1038/srep06434
M3 - Journal article
C2 - 25242624
AN - SCOPUS:84923304409
VL - 4
JO - Scientific Reports
JF - Scientific Reports
SN - 2045-2322
M1 - 6434
ER -
ID: 172128493