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

نویسندگان

  • Xiaolin Li
  • Evandro Fei Fang
  • Morten Scheibye-Knudsen
  • Honghua Cui
  • Lu Qiu
  • Jian Li
  • Yuping He
  • Jing Huang
  • Vilhelm A. Bohr
  • Tzi Bun Ng
  • Hongwei Guo
چکیده

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.

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Chronic Effects of Di(2-ethylhexyl)phthalate on Stereological Parameters of Testis in Adult Wistar Rats

Objective(s) In recent years concerns have been raised regarding the incidence of male reproductive disorders from exposure to endocrine disruptors. So, chronic effects of di(2-ethylhexyl)phthalate were studied on histological and stereological structure of testis in adult Wistar rats. Materials and Methods Thirty two adult Wistar rats were randomly divided in four equal experiment groups; o...

متن کامل

The Effect of Di-(2-Ethylhexyl) Phthalate (DEHP) on Mouse Daily Sperm Production and Epididymal Sperm Parameters

Purpose: The purpose of this study is to evaluate the effect of Di-(2-ethylhexyl) phthalate (DEHP) on testicular spermatid number per gram testis (TSN), daily sperm production (DSP), count, motility, viability, morphology, and chromatine quality of epididymal sperm. Materials and Methods: The protocol for DEHP administration was that adult male NMRI mice (the age group of 4 weeks) received 29 D...

متن کامل

Role of oxidative stress in germ cell apoptosis induced by di(2-ethylhexyl)phthalate.

Phthalate esters have been used extensively as plasticizers of synthetic polymers. Recent studies have revealed that these esters induce atrophy of the testis, although its pathogenesis remains unknown. The present study describes the possible involvement of oxidative stress in the pathogenesis of atrophy of the rat testis induced by di(2-ethylhexyl)phthalate (DEHP). Biochemical and immunohisto...

متن کامل

Evaluation of cytotoxicity and oxidative DNA damaging effects of di(2-ethylhexyl)-phthalate (DEHP) and mono(2-ethylhexyl)-phthalate (MEHP) on MA-10 Leydig cells and protection by selenium.

Di(2-ethylhexyl)-phthalate (DEHP) is the most abundantly used phthalate derivative, inevitable environmental exposure of which is suspected to contribute to the increasing incidence of testicular dysgenesis syndrome in humans. Oxidative stress and mitochondrial dysfunction in germ cells are suggested to contribute to phthalate-induced disruption of spermatogenesis in rodents, and Leydig cells a...

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

برای دانلود متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

عنوان ژورنال:

دوره 4  شماره 

صفحات  -

تاریخ انتشار 2014