Testicular toxicity of profenofos in matured male rats.
To investigate the effect of the phosphorothoate insecticide profenofos on male specific gene expression on rat testis, 16-week-old Wistar rats were orally administered at dose of 17.8 mg/kg twice weekly for 65 days. Gene expression in the testes was monitored by DNA microarray analysis and real-time RT-PCR, which revealed that genes related to steroidogenesis including cytochrome P450 17A1 (CYP17A1), steroidogenic acute regulatory protein (StAR) and CYP11A1 were significantly increased. Besides the testes were histopathologicaly examined, which revealed testicular destruction and degeneration represented by a layer of columnar epithelium, oedematous changes surrounding the seminiferous tubules besides vacuolated spermatogonial cells and more elongated Leydig cells. These data suggest that profenofos considered as one of the male reproductive toxicants. Furthermore, we propose that the above three steroidogenic-related genes and the gene of acrosomal reaction as potential biomarkers of testicular toxicity.
Moustafa
Gihan Gamal
GG
Laboratory of Toxicology, Department of Environmental Veterinary Sciences, Graduate School of Veterinary Medicine, Hokkaido University, N18, W9, Kita-ku, Sapporo, 060-0818, Japan.
Ibrahim
Zein Shaban
ZS
Hashimoto
Yoshiharu
Y
Alkelch
Alkelch M
AM
Sakamoto
Kentaro Q
KQ
Ishizuka
Mayumi
M
Fujita
Shoichi
S
D000284:Administration, Oral; D000367:Age Factors; D000818:Animals; D002786:Cholesterol Side-Chain Cleavage Enzyme / Q000235:genetics; D020869:Gene Expression Profiling / Q000379:methods; D005786:Gene Expression Regulation / Q000187:drug effects*; D007306:Insecticides / Q000008:administration & dosage / Q000633:toxicity; D007985:Leydig Cells / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D008297:Male; D046529:Microscopy, Electron, Transmission; D020411:Oligonucleotide Array Sequence Analysis / Q000379:methods; D063086:Organothiophosphates / Q000008:administration & dosage / Q000633:toxicity*; D010750:Phosphoproteins / Q000235:genetics; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013087:Spermatids / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013093:Spermatogonia / Q000187:drug effects / Q000473:pathology / Q000648:ultrastructure; D013254:Steroid 17-alpha-Hydroxylase / Q000235:genetics; D013737:Testis / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D013739:Testosterone / Q000097:blood; D018675:Toxicity Tests / Q000379:methods; D000098682:Steroidogenic Acute Regulatory Protein
D007306:Insecticides; D063086:Organothiophosphates; D010750:Phosphoproteins; D000098682:Steroidogenic Acute Regulatory Protein; D013739:Testosterone; C024273:profenofos; C501892:CYP17A1 protein, human; D013254:Steroid 17-alpha-Hydroxylase; D002786:Cholesterol Side-Chain Cleavage Enzyme