Effects of intrauterine growth restriction during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver
Effects of intrauterine growth restriction during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver
复制标题
妊娠晚期宫内生长受限对羊胎肝细胞凋亡及相关基因表达的影响
DOI：
10.1016/j.theriogenology.2016.11.030
复制
发表时间：
2017-03-01
期刊：
影响因子：
2.8
通讯作者：
Ao, Changjin
中科院分区：
文献类型：
--
作者：
Liu, Yingchun;Ma, Chi;Ao, Changjin
研究妊娠晚期宫内生长受限（IUGR）对绵羊胎肝细胞凋亡及相关基因表达的影响。将18只同期交配的单胎蒙古母羊在妊娠d90时分为3组：受限组1（RG 1，0.18 MJ ME kg BW-0.75 d（-1），n = 6），限制组2（RG 2，0.33 MJ ME kg BW-0.75 d（-1），n = 6）和对照组（CG，自由采食，0.67 MJ ME kg BW-0.75 d（-1），n = 6）。在第140天屠宰时回收胎仔。检测胎肝重量、DNA含量和蛋白/DNA比值、增殖指数、细胞色素c、Caspase-3、8和9活性沿着凋亡相关基因的相对表达。与对照组相比，两个限制组的胎仔体重、肝重、DNA含量和蛋白/DNA比值均降低（P < 0.05），增殖指数也降低（P < 0.05）。两限制组胎肝细胞凋亡率均明显高于对照组（P < 0.05）。重度IUGR组（RG 1）的Caspase-3、8、9活性显著升高（P < 0.05），线粒体细胞色素c水平显著升高（P < 0.05）; RG 2组的Caspase-3、8、9活性也有中等程度的变化，但差异无统计学意义（P> 0.05）。肝细胞凋亡相关基因表达：RG 1、RG 2组P21蛋白、Bcl-2蛋白、FasL蛋白表达均明显降低（P < 0.05）。两组IUGR胎儿肝脏P53蛋白、Bcl-2相关X蛋白和凋亡抗原1（Fas）的表达均高于对照组（P < 0.05）。结果表明，胎儿肝细胞增殖阻滞于G1期，胎儿肝细胞凋亡对母体营养不良所致IUGR敏感。IUGR胎肝细胞凋亡是IUGR胎肝增殖迟缓、发育不良的重要机制。(C)2016 Elsevier Inc. All rights reserved.
This study investigated the effect of intrauterine growth restriction (IUGR) during late pregnancy on the cell apoptosis and related gene expression in ovine fetal liver. Eighteen time-mated Mongolian ewes with singleton fetuses were allocated to three groups at d 90 of pregnancy: Restricted Group 1 (RG1, 0.18 MJ ME kg BW-0.75 d(-1), n = 6), Restricted Group 2 (RG2, 0.33 MJ ME kg BW-0.75 d(-1), n = 6) and a Control Group (CG, ad libitum, 0.67 MJ ME kg BW-0.75 d(-1)1, n = 6). Fetuses were recovered at slaughter on d 140. Fetal liver weight, DNA content and protein/DNA ratio, proliferation index, cytochrome c, activities of Caspase-3, 8, and 9 were examined, along with relative expression of genes related to apoptosis. Fetuses in both restricted groups exhibited decreased BW, hepatic weight, DNA content, and protein/DNA ratio when compared to CG (P < 0.05), as well as reduced proliferation index (P < 0.05). However, the increased numbers of apoptotic cells in fetal liver were observed in both restricted groups (P < 0.05). Fetuses with severe IUGR (RG1) exhibited increased (P < 0.05) activities of Caspase-3, 8, 9, as higher levels of mitochondrial cytochrome c in fetal liver; intermediate changes were found in RG2 fetuses, but the difference were not significant (P> 0.05). Hepatic expression of gene related to apoptosis showed reduced protein 21 (P21), B-cell lymphoma 2 (Bcl-2) and apoptosis antigen I ligand (FasL) expression in RG1 and RG2 (P < 0.05). In contrast, the increased hepatic expression of protein 53 (P53), Bcl-2 associated X protein (Bax) and apoptosis antigen 1 (Fas) in both IUGR fetuses were found (P < 0.05). These results indicate that the fetal hepatocyte proliferation were arrested in G1 cell cycle, and the fetal hepatocyte apoptosis was sensitive to the IUGR resulted from maternal undernutrition. The cell apoptosis in IUGR fetal liver were the potential mechanisms for its retarded proliferation and impaired development. (C) 2016 Elsevier Inc. All rights reserved.