The acute effects of mono(2-ethylhexyl)phthalate (MEHP) on testes of prepubertal Wistar rats.
A single oral dose of 400 mg/kg body weight of mono(2-ethylhexyl)phthalate (MEHP), the testis toxic metabolite of di(2-ethylhexyl)phthalate, was given to 28-day-old male Wistar rats and the testis toxic effects were investigated 3,6, and 12 h after exposure. Detachment and sloughing of germ cells were observed, and in the Sertoli cells the cytoplasmatic intermediate filament vimentin collapsed. In the immunohistochemical investigation the androgen receptor distribution was unchanged between the control group and treated groups. The expression of the testosterone-repressed-prostatic-message-2 gene in rat testis increased after 3 h, but returned to control levels after 6 and 12 h. Caspase-3 activity increased 3 and 12 h after MEHP exposure. This increase could not be correlated to an increase in DNA fragmentation or increase in apoptotic numbers of germ cells. In conclusion, the effect of MEHP in testis is apparently not involving the androgen receptor. Vimentin localisation in the Sertoli cells, and increased levels of caspase-3 activity appear to be sensitive and early markers of MEHP testis toxicity.
Dalgaard
M
M
Danish Veterinary and Food Administration, Institute of Food Safety and Toxicology, Mørkhøj Bygade 19, 2860 Søborg, Denmark. mac@fdir.dk
Nellemann
C
C
Lam
H R
HR
Sørensen
I K
IK
Ladefoged
O
O
D000818:Animals; D017209:Apoptosis / Q000235:genetics; D053148:Caspase 3; D020169:Caspases / Q000235:genetics / Q000378:metabolism; D051152:Clusterin; D004247:DNA / Q000187:drug effects / Q000378:metabolism; D004051:Diethylhexyl Phthalate / Q000031:analogs & derivatives / Q000633:toxicity*; D005786:Gene Expression Regulation / Q000187:drug effects; D006023:Glycoproteins / Q000235:genetics / Q000378:metabolism; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D008297:Male; D018832:Molecular Chaperones / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013997:Time Factors; D014746:Vimentin / Q000378:metabolism
D051152:Clusterin; D006023:Glycoproteins; D018832:Molecular Chaperones; D014746:Vimentin; D004247:DNA; D004051:Diethylhexyl Phthalate; C505410:Casp3 protein, rat; D053148:Caspase 3; D020169:Caspases; C016599:mono-(2-ethylhexyl)phthalate