title: Overexpression of thioredoxin-1 reduces oxidative stress in the placenta of transgenic mice and promotes fetal growth via glucose metabolism.
abstract: Oxidative stress occurs where there is an imbalance between the production and scavenging of free radicals. Pregnancy per se is a state of oxidative stress due to the increased metabolic activity of placental mitochondria and reduced scavenging ability of antioxidant systems. Overproduction of reactive oxygen species may be associated with impaired fetal growth. However, the physiological influence of antioxidant systems on fetal growth is not well understood. In this study we assessed the effects of antioxidant systems on fetal growth using human thioredoxin (hTRX)-1 overexpressing transgenic (Tg) mice. Tg or C57BL/6 [wild-type (WT)] male mice were mated with WT female mice, and dams were killed to obtain the fetuses and placentas on gestational d 15. Tg fetuses were significantly heavier than WT fetuses, whereas placental weight did not differ significantly between the two groups. Immunohistochemically, hTRX-1 was localized to the nuclei of labyrinthine trophoblasts in Tg mice. In addition, placental expression of 8-hydroxy-2'-deoxyguanosine, which reflects DNA damage caused by oxidative stress, was reduced in Tg mice compared with WT mice. Placental expression of glucose transporter-1 mRNA and protein was significantly higher in Tg mice than WT mice, whereas no significant differences were observed for glucose transporter-3, IGF, and IGF-binding protein mRNA expression. These results suggest that placental and/or systemic antioxidant systems can influence fetal growth. In particular, increased hTRX-1 activity and the resulting modified placental redox state may play an important role in fetal growth by increasing the availability of glucose.
authors.affiliation: Department of Obstetrics and Gynecology, Mie University Graduate School of Medicine, 2-174 Edobashi, Tsu, Mie 514-8507, Japan. umkwtks@clin.medic.mie-u.ac.jp
authors.forename: Takashi
authors.initials: T
authors.lastname: Umekawa
authors.forename: Takashi
authors.initials: T
authors.lastname: Sugiyama
authors.forename: Tomohisa
authors.initials: T
authors.lastname: Kihira
authors.forename: Nao
authors.initials: N
authors.lastname: Murabayashi
authors.forename: Lingyun
authors.initials: L
authors.lastname: Zhang
authors.forename: Kenji
authors.initials: K
authors.lastname: Nagao
authors.forename: Yuki
authors.initials: Y
authors.lastname: Kamimoto
authors.forename: Ning
authors.initials: N
authors.lastname: Ma
authors.forename: Junji
authors.initials: J
authors.lastname: Yodoi
authors.forename: Norimasa
authors.initials: N
authors.lastname: Sagawa
mesh_terms: D000818:Animals; D005260:Female; D047109:Fetal Development / Q000235:genetics*; D015971:Gene Expression Regulation, Enzymologic; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1 / Q000235:genetics / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D010084:Oxidation-Reduction; D018384:Oxidative Stress / Q000235:genetics*; D010920:Placenta / Q000378:metabolism*; D010929:Placentation; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013879:Thioredoxins / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D015854:Up-Regulation
chemical_list: D051272:Glucose Transporter Type 1; D012333:RNA, Messenger; C495678:Slc2a1 protein, mouse; C491203:TXN protein, human; D013879:Thioredoxins; D005947:Glucose