TY - JOUR
T1 - Role of phospholipase D in regulation of testicular Leydig cell hyperplasia in Sprague-Dawley rats treated with di(2-ethylhexyl) phthalate
AU - Lee, Young Jun
AU - Ahn, Mee Young
AU - Kim, Hyung Sik
AU - Kwack, Seung Jun
AU - Park, Kul Lea
AU - Yoon, Sik
AU - Min, Dosik
PY - 2011/8
Y1 - 2011/8
N2 - This study was conducted to determine the functional role of phospholipase D (PLD) involved in testicular Leydig cell damage caused by di (2-ethylhexyl) phthalate (DEHP) in Sprague-Dawley rats. DEHP (500 mg/kg/day) was administered orally to prepubertal rats for 1, 7, 14, 21 or 28 days. After 7 days of exposure, DEHP produced morphological changes in the testis, including alterations in seminiferous tubule diameters and loss of spermatogenic cells. Immunohistochemistry (IHC) analyses revealed that DEHP increased Leydig cell number in the testes as well as significantly increased the expression of PLD1/2 in Leydig cells after 7 days of exposure. Furthermore, the protein levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) increased in a similar manner to the PLD1/2 expression patterns. DEHP significantly reduced the expression of sperm-associated antigen 4 (Spag4) and lactate dehydrogenase A (LDHA) mRNA. In contrast, there was a significant increase in the expression of steroidogenic acute regulatory (StAR) mRNA against DEHP in a time-dependent manner, but serum testosterone concentration was decreased. These findings demonstrate that DEHP induces PLD expression in the testicular Leydig cells; this plays a key role in hyperplasia of Leydig cells and steroidogenic pathway via pERK1/2 activation.
AB - This study was conducted to determine the functional role of phospholipase D (PLD) involved in testicular Leydig cell damage caused by di (2-ethylhexyl) phthalate (DEHP) in Sprague-Dawley rats. DEHP (500 mg/kg/day) was administered orally to prepubertal rats for 1, 7, 14, 21 or 28 days. After 7 days of exposure, DEHP produced morphological changes in the testis, including alterations in seminiferous tubule diameters and loss of spermatogenic cells. Immunohistochemistry (IHC) analyses revealed that DEHP increased Leydig cell number in the testes as well as significantly increased the expression of PLD1/2 in Leydig cells after 7 days of exposure. Furthermore, the protein levels of phosphorylated extracellular signal-regulated kinase 1/2 (pERK1/2) increased in a similar manner to the PLD1/2 expression patterns. DEHP significantly reduced the expression of sperm-associated antigen 4 (Spag4) and lactate dehydrogenase A (LDHA) mRNA. In contrast, there was a significant increase in the expression of steroidogenic acute regulatory (StAR) mRNA against DEHP in a time-dependent manner, but serum testosterone concentration was decreased. These findings demonstrate that DEHP induces PLD expression in the testicular Leydig cells; this plays a key role in hyperplasia of Leydig cells and steroidogenic pathway via pERK1/2 activation.
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U2 - 10.1007/s00204-010-0618-5
DO - 10.1007/s00204-010-0618-5
M3 - Article
C2 - 21079920
AN - SCOPUS:80052711723
SN - 0340-5761
VL - 85
SP - 975
EP - 985
JO - Archives of Toxicology
JF - Archives of Toxicology
IS - 8
ER -