Differential effects of phthalates on the testis and the liver

Nandini Bhattacharya; Jannette M Dufour; My-Nuong Vo; Janice Okita; Richard Okita; Kwan Hee Kim

doi:10.1095/biolreprod.104.031583

Back

Differential effects of phthalates on the testis and the liver

Journal article

Open access

Peer reviewed

Differential effects of phthalates on the testis and the liver

Nandini Bhattacharya, Jannette M Dufour, My-Nuong Vo, Janice Okita, Richard Okita and Kwan Hee Kim

Biology of reproduction, Vol.72(3), pp.745-754

03/2005

DOI: https://doi.org/10.1095/biolreprod.104.031583

Handle:

https://hdl.handle.net/2376/112998

PMID: 15564602

Files and links (1)

url

https://doi.org/10.1095/biolreprod.104.031583View

Published (Version of record) Open

Abstract

Receptors, Retinoic Acid - drug effects

PPAR gamma - drug effects

Testis - cytology

Apoptosis - drug effects

Phthalic Acids - toxicity

Germ Cells - drug effects

Rats

Male

Sertoli Cells - drug effects

Testis - drug effects

Animals

Liver - drug effects

Signal Transduction - drug effects

Liver - cytology

Environmental Pollutants - toxicity

Mitogen-Activated Protein Kinases - drug effects

Retinoic Acid Receptor alpha

Hepatocytes - drug effects

Phthalates have been shown to elicit contrasting effects on the testis and the liver, causing testicular degeneration and promoting abnormal hepatocyte proliferation and carcinogenesis. In the present study, we compared the effects of phthalates on testicular and liver cells to better understand the mechanisms by which phthalates cause testicular degeneration. In vivo treatment of rats with di-(2-ethylhexyl) phthalate (DEHP) caused a threefold increase of germ cell apoptosis in the testis, whereas apoptosis was not changed significantly in livers from the same animals. Western blot analyses revealed that peroxisome proliferator-activated receptor (PPAR) alpha is equally abundant in the liver and the testis, whereas PPAR gamma and retinoic acid receptor (RAR) alpha are expressed more in the testis. To determine whether the principal metabolite of DEHP, mono-(2-ethylhexyl) phthalate (MEHP), or a strong peroxisome proliferator, 4-chloro-6(2,3-xylindino)-2-pyrimidinylthioacetic acid (Wy-14,643), have a differential effect in Sertoli and liver cells by altering the function of RAR alpha and PPARs, their nuclear trafficking patterns were compared in Sertoli and liver cells after treatment. Both MEHP and Wy-14,643 increased the nuclear localization of PPAR alpha and PPAR gamma in Sertoli cells, but they decreased the nuclear localization of RAR alpha, as previously shown. Both PPAR alpha and PPAR gamma were in the nucleus and cytoplasm of liver cells, but RAR alpha was predominant in the cytoplasm, regardless of the treatment. At the molecular level, MEHP and Wy-14,643 reduced the amount of phosphorylated mitogen-activated protein kinase (activated MAPK) in Sertoli cells. In comparison, both MEHP and Wy-14,643 increased phosphorylated MAPK in liver cells. These results suggest that phthalates may cause contrasting effects on the testis and the liver by differential activation of the MAPK pathway, RAR alpha, PPAR alpha, and PPAR gamma in these organs.

Metrics

17 Record Views

See more details

Details

Title: Differential effects of phthalates on the testis and the liver
Creators: Nandini Bhattacharya - School of Molecular Biosciences, Center for Reproductive Biology, Washington State University, Pullman, Washington 99164, USA
Jannette M Dufour
My-Nuong Vo
Janice Okita
Richard Okita
Kwan Hee Kim
Publication Details: Biology of reproduction, Vol.72(3), pp.745-754
Publisher: United States
Grant note: ES09978 / NIEHS NIH HHS
Identifiers: 99900548094601842
Language: English
Resource Type: Journal article