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J.Health Sci., 55(3), 380-388, 2009
Effects of Di(2-ethylhexyl) Phthalate on Regulation of Steroidogenesis or Spermatogenesis in Testes of Sprague-Dawley Rats
Young Jun Lee,a Ena Lee,a
Tae Hyung Kim,a Jae Seok Choi,a
Jaewon Lee,a Ki Kyung Jung,b
Seung Jun Kwack,b Kyu Bong Kim,b
Tae Seok Kang,b Soon Young Han,b
Byung Mu Lee,c and Hyung Sik Kim*, a
aCollege of Pharmacy, Pusan National University, San 30, Jangjeun-dong, Geumjeung-gu, Busan 609-735, South Korea,
bNational Institute of Toxicological Research, Korea Food and Drug Administration, 5 Nokbun-dong, Eunpyung-ku, Seoul 122-704, Korea and
cDivision of Toxicology, College of Pharmacy, Sungkyunkwan University, Chunchun-Dong 300, Changan-Ku, Kyunggi-Do, Suwon, 440-746, South Korea
Di(2-ethylhexyl) phthalate (DEHP) used as a common plasticizer additive in the manufacture of plastics, such as polyvinyl chloride (PVC). This study examined the effect of DEHP on steroidogenesis or spermatogenesis in the testes of Sprague-Dawley male rats treated orally with 250, 500, 750 mg/kg over a 30-day period. The expression levels of the steroidogenic- or spermatogenic-related genes were analyzed in the testis using a reverse transcription-polymerase chain reaction (RT-PCR) and Western blot analysis. High doses of DEHP (500 and 750 mg/kg) significantly decreased the testicular sperm counts and daily sperm production (DSP). In addition, serum testosterone levels were significantly lower in the DEHP treatment groups than in the control. The mRNA levels of SR-B1, StAR, PBR and CYP17 increased in a dose-dependent manner. These increases were significant at 500 and 750 mg/kg. In the other hand, the mRNA levels of CYP19 decreased significantly in testes of rats exposed to DEHP 500 and 750 mg/kg. Dose-dependent decreases in Spag4 and LDHA mRNA in the testis were observed after DEHP exposure, while there was a significant decrease in thyroid hormone receptor (TR)α1 protein levels. High doses of DEHP significantly increased the expression of peroxisome proliferator-activated receptor (PPAR)-r and retinoid X receptor (RXR)-α protein but markedly decreased the expression of RXR-r. These results suggest that DEHP exposure can alter the expression of the spermatogenic- or steroidogenic-related genes resulting in a decrease in sperm production in the testis. This study is expected to be helpful in research examining the mechanisms for how DEHP reduces the expression pattern of the genes involved steroid hormone synthesis after chronic exposure to DEHP.
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