Microarray analysis of T-2 toxin-induced liver, placenta and fetal liver lesions in pregnant rats.
Pregnant rats on day 13 of gestation were treated orally with 2 mg/kg of T-2 toxin and sacrificed at 1, 3, 6, 9 and 12 h after the treatment (HAT). Histopathologically, the number of apoptotic cells was increased in the liver, placenta and fetal liver (peaked at 6, 12 and 9-12 HAT, respectively). To examine the gene expression profiles, we performed microarray analysis of these tissues at two selected time points based on the results of the TdT-mediated dUTP nick end labeling (TUNEL) staining. Increased expression of oxidative stress- and apoptosis-related genes was detected in the liver of dams, placenta and fetal liver of pregnant rats treated with T-2 toxin at the peak time point of apoptosis. Decreased expression of lipid metabolism- and drug-metabolizing enzyme-related genes was also detected in these tissues. The results suggested that the mitogen-activated protein kinase (MAPK) pathway might be involved in the mechanism of T-2 toxin-induced apoptosis. In addition, increased expression of the c-jun gene was consistently observed in these tissues. Our results suggest that the mechanism of T-2 toxin-induced toxicity in pregnant rats is due to oxidative stress followed by the activation of the MAPK pathway, finally inducing apoptosis. The c-jun gene may play an important role in T-2 toxin-induced apoptosis.
Sehata
Shinya
S
Medicinal Safety Research Laboratories, Sankyo Co., Ltd., 717 Horikoshi, Fukuroi-shi, Shizuoka 437-0065, Japan. sehata@sankyo.co.jp
Kiyosawa
Naoki
N
Atsumi
Fusako
F
Ito
Kazumi
K
Yamoto
Takashi
T
Teranishi
Munehiro
M
Uetsuka
Koji
K
Nakayama
Hiroyuki
H
Doi
Kunio
K
D000284:Administration, Oral; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D005260:Female; D005333:Fetus / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D020869:Gene Expression Profiling; D018507:Gene Expression Regulation, Developmental / Q000187:drug effects*; D016758:Genes, jun; D020287:In Situ Nick-End Labeling; D008099:Liver / Q000187:drug effects* / Q000196:embryology / Q000378:metabolism / Q000473:pathology; D018811:Maternal Exposure; D020928:Mitogen-Activated Protein Kinases / Q000187:drug effects / Q000235:genetics; D018384:Oxidative Stress; D010920:Placenta / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D011247:Pregnancy; D040081:Protein Array Analysis; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013605:T-2 Toxin / Q000633:toxicity*
D012333:RNA, Messenger; D020928:Mitogen-Activated Protein Kinases; D013605:T-2 Toxin