Thioredoxin, an anti-oxidant protein, protects mouse embryos from oxidative stress-induced developmental anomalies.
During the early postimplantation period, rodent embryos survive in a relatively anaerobic environment in utero and are vulnerable to a high oxygen pressure. They become resistant to oxygen stress when they are exposed to a higher oxygen pressure after the uteroplacental circulation is established. However, it is unknown how embryos acquire such resistance against oxidative stress. This study was undertaken to examine whether an antioxidant protein thioredoxin (TRX) plays a significant role in the embryonic acquisition of the tolerance to oxidative stress. E7.5 embryos of C57BL/6 wild-type (WT) and human TRX (hTRX) inserted-transgenic (Tg) embryos were cultured under 10 or 25% O2 and their growth and morphological differentiation were evaluated. The TRX expression and the products of oxidative stress (8-hydroxy-2'-deoxy-guanosine and carbonylated proteins) in their tissues were also examined. When WT embryos were cultivated in vitro under 25% O2, their growth was significantly disturbed and various developmental abnormalities were induced, which did not occur in embryos grown under 10% O2. However, such embryotoxic effects of oxygen were significantly attenuated in the hTRX Tg embryos that continuously express hTRX. Accumulation of the products of oxidative stress was significantly reduced in hTRX Tg embryos as compared with that in WT embryos. The TRX transgene appears to provide the embryo with the resistance against oxidative stress and may play a crucial role in the redox regulation in embryos.
Kobayashi-Miura
Mikiko
M
Department of Anatomy and Developmental Biology, Graduate School of Medicine, Kyoto University, Kyoto 606-8501, Japan.
Nakamura
Hajime
H
Yodoi
Junji
J
Shiota
Kohei
K
D000080242:8-Hydroxy-2'-Deoxyguanosine; D000014:Abnormalities, Drug-Induced / Q000209:etiology / Q000378:metabolism / Q000517:prevention & control*; D000818:Animals; D000975:Antioxidants / Q000378:metabolism*; D015153:Blotting, Western; D046508:Culture Techniques; D003849:Deoxyguanosine / Q000031:analogs & derivatives* / Q000378:metabolism; D004622:Embryo, Mammalian / Q000187:drug effects*; D005314:Embryonic and Fetal Development / Q000502:physiology*; D005260:Female; D006801:Humans; D007124:Immunoenzyme Techniques; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D018384:Oxidative Stress; D010100:Oxygen / Q000009:adverse effects / Q000378:metabolism / Q000494:pharmacology / Q000633:toxicity*; D011247:Pregnancy; D017382:Reactive Oxygen Species / Q000494:pharmacology; D013879:Thioredoxins / Q000378:metabolism*; D018808:Transcription Factor AP-1 / Q000378:metabolism
D000975:Antioxidants; D017382:Reactive Oxygen Species; D018808:Transcription Factor AP-1; D013879:Thioredoxins; D000080242:8-Hydroxy-2'-Deoxyguanosine; D003849:Deoxyguanosine; D010100:Oxygen