Role of phospholipase D in regulation of testicular Leydig cell hyperplasia in Sprague-Dawley rats treated with di(2-ethylhexyl) phthalate

Young Jun Lee, Mee Young Ahn, Hyung Sik Kim, Seung Jun Kwack, Kul Lea Park, Sik Yoon, Dosik Min

Research output: Contribution to journalArticle

8 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)975-985
Number of pages11
JournalArchives of Toxicology
Volume85
Issue number8
DOIs
Publication statusPublished - 2011 Aug 1

Fingerprint

Phospholipase D
Leydig Cells
Hyperplasia
Sprague Dawley Rats
Rats
Mitogen-Activated Protein Kinase 3
Mitogen-Activated Protein Kinase 1
Testis
Messenger RNA
Seminiferous Tubules
phthalic acid
Testosterone
Spermatozoa
Cell Count
Chemical activation
Immunohistochemistry
Cells
Antigens
Serum

All Science Journal Classification (ASJC) codes

  • Toxicology
  • Health, Toxicology and Mutagenesis

Cite this

Lee, Young Jun ; Ahn, Mee Young ; Kim, Hyung Sik ; Kwack, Seung Jun ; Park, Kul Lea ; Yoon, Sik ; Min, Dosik. / Role of phospholipase D in regulation of testicular Leydig cell hyperplasia in Sprague-Dawley rats treated with di(2-ethylhexyl) phthalate. In: Archives of Toxicology. 2011 ; Vol. 85, No. 8. pp. 975-985.
@article{09139abd38ea48e6adb3d3e074a89093,
title = "Role of phospholipase D in regulation of testicular Leydig cell hyperplasia in Sprague-Dawley rats treated with di(2-ethylhexyl) phthalate",
abstract = "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.",
author = "Lee, {Young Jun} and Ahn, {Mee Young} and Kim, {Hyung Sik} and Kwack, {Seung Jun} and Park, {Kul Lea} and Sik Yoon and Dosik Min",
year = "2011",
month = "8",
day = "1",
doi = "10.1007/s00204-010-0618-5",
language = "English",
volume = "85",
pages = "975--985",
journal = "Archiv fur Toxikologie",
issn = "0003-9446",
publisher = "Springer Verlag",
number = "8",

}

Role of phospholipase D in regulation of testicular Leydig cell hyperplasia in Sprague-Dawley rats treated with di(2-ethylhexyl) phthalate. / Lee, Young Jun; Ahn, Mee Young; Kim, Hyung Sik; Kwack, Seung Jun; Park, Kul Lea; Yoon, Sik; Min, Dosik.

In: Archives of Toxicology, Vol. 85, No. 8, 01.08.2011, p. 975-985.

Research output: Contribution to journalArticle

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 - 2011/8/1

Y1 - 2011/8/1

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.

UR - http://www.scopus.com/inward/record.url?scp=80052711723&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=80052711723&partnerID=8YFLogxK

U2 - 10.1007/s00204-010-0618-5

DO - 10.1007/s00204-010-0618-5

M3 - Article

C2 - 21079920

AN - SCOPUS:80052711723

VL - 85

SP - 975

EP - 985

JO - Archiv fur Toxikologie

JF - Archiv fur Toxikologie

SN - 0003-9446

IS - 8

ER -