Prolonged endoplasmic reticulum stress alters placental morphology and causes low birth weight
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- 作者：Takashige Kawakami ; tkawakami@ph.bunri-u.ac.jp" class="auth_mail ; Masaki Yoshimi ; Yoshito Kadota ; Masahisa Inoue ; Masao Sato ; Shinya Suzuki
- 关键词：ATF6 ; activating transcription factor 6 ; BiP ; binding immunoglobulin protein ; BW ; body weight ; CHOP ; CCAAT-enhancer-binding protein homologous protein ; DMSO ; dimethyl sulfoxide ; ELISA ; enzyme-linked immunosorbent assay ; ER ; endoplasmic reticulum ; FGR ; fetal growth restriction ; GD ; gestation day ; GLUT ; glucose transporter ; GRP78 ; glucose-regulated protein 78 ; HIF-1伪 ; hypoxia inducible factor 1 ; alpha subunit ; HE ; hematoxylin and eosin ; IRE1伪 ; inositol-requiring enzyme 1伪 ; IUGR ; intrauterine gr
- 刊名：Toxicology and Applied Pharmacology
- 出版年：1 March, 2014
- 年：2014
- 卷：275
- 期：2
- 页码：134-144
- 全文大小：1861 K
文摘
The role of endoplasmic reticulum (ER) stress in pregnancy remains largely unknown. Pregnant mice were subcutaneously administered tunicamycin (Tun), an ER stressor, as a single dose [0, 50, and 100 渭g Tun/kg/body weight (BW)] on gestation days (GDs) 8.5, 12.5, and 15.5. A high incidence (75%) of preterm delivery was observed only in the group treated with Tun 100 渭g/kg BW at GD 15.5, indicating that pregnant mice during late gestation are more susceptible to ER stress on preterm delivery. We further examined whether prolonged in utero exposure to ER stress affects fetal development. Pregnant mice were subcutaneously administered a dose of 0, 20, 40, and 60 渭g Tun/kg from GD 12.5 to 16.5. Tun treatment decreased the placental and fetal weights in a dose-dependent manner. Histological evaluation showed the formation of a cluster of spongiotrophoblast cells in the labyrinth zone of the placenta of Tun-treated mice. The glycogen content of the fetal liver and placenta from Tun-treated mice was lower than that from control mice. Tun treatment decreased mRNA expression of Slc2a1/glucose transporter 1 (GLUT1), which is a major transporter for glucose, but increased placental mRNA levels of Slc2a3/GLUT3. Moreover, maternal exposure to Tun resulted in a decrease in vascular endothelial growth factor receptor-1 (VEGFR-1), VEGFR-2, and placental growth factor. These results suggest that excessive and exogenous ER stress may induce functional abnormalities in the placenta, at least in part, with altered GLUT and vascular-related gene expression, resulting in low infant birth weight.