Nüsken Eva, Gellhaus Alexandra, Kühnel Elisabeth, Swoboda Isabelle, Wohlfarth Maria, Vohlen Christina, Schneider Holm, Dötsch Jörg, Nüsken Kai-Dietrich
Department of Pediatrics, Medical Faculty, University of Cologne, Cologne, Germany.
Department of Pediatrics, University of Erlangen-Nuremberg, Erlangen, Germany.
J Cell Biochem. 2016 Jul;117(7):1594-603. doi: 10.1002/jcb.25450. Epub 2015 Dec 14.
Regulation of placental nutrient transport significantly affects fetal development and may modify intrauterine growth restriction (IUGR) and fetal programming. We hypothesized that placental nutrient transporters are differentially affected both by utero-placental insufficiency and prenatal surgical stress. Pregnant rats underwent bilateral uterine artery and vein ligation (LIG), sham operation (SOP) or no operation (controls, C) on gestational day E19. Placentas were obtained by caesarean section 4 h (LIG, n=20 placentas; SOP, n=24; C, n=12), 24 h (LIG, n=28; SOP, n=20; C, n=12) and 72 h (LIG, n=20; SOP, n=20; C, n=24) after surgery. Gene and protein expression of placental nutrient transporters for fatty acids (h-FABP, CD36), amino acids (SNAT1, SNAT2) and glucose (GLUT-1, Connexin 26) were examined by qRT-PCR, western blot and immunohistochemistry. Interestingly, the mean protein expression of h-FABP was doubled in placentas of LIG and SOP animals 4, 24 (SOP significant) and 72 h (SOP significant) after surgery. CD36 protein was significantly increased in LIG after 72 h. SNAT1 and SNAT2 protein and gene expressions were significantly reduced in LIG and SOP after 24 h. Further significantly reduced proteins were GLUT-1 in LIG (4 h, 72 h) and SOP (24 h), and Connexin 26 in LIG (72 h). In conclusion, placental nutrient transporters are differentially affected both by reduced blood flow and stress, probably modifying the already disturbed intrauterine milieu and contributing to IUGR and fetal programming. Increased fatty acid transport capacity may affect energy metabolism and could be a compensatory reaction with positive effects on brain development. J. Cell. Biochem. 117: 1594-1603, 2016. © 2015 Wiley Periodicals, Inc.
胎盘营养物质转运的调节显著影响胎儿发育,并可能改变宫内生长受限(IUGR)和胎儿编程。我们假设胎盘营养转运蛋白受子宫 - 胎盘功能不全和产前手术应激的影响存在差异。妊娠大鼠在妊娠第E19天接受双侧子宫动脉和静脉结扎(LIG)、假手术(SOP)或不做手术(对照组,C)。在手术后4小时(LIG,n = 20个胎盘;SOP,n = 24;C,n = 12)、24小时(LIG,n = 28;SOP,n = 20;C,n = 12)和72小时(LIG,n = 20;SOP,n = 20;C,n = 24)通过剖宫产获取胎盘。通过qRT - PCR、蛋白质印迹法和免疫组织化学检测胎盘脂肪酸(h - FABP、CD36)、氨基酸(SNAT1、SNAT2)和葡萄糖(GLUT - 1、连接蛋白26)营养转运蛋白的基因和蛋白质表达。有趣的是,在手术后4小时、24小时(SOP组显著)和72小时(SOP组显著),LIG组和SOP组动物胎盘中h - FABP的平均蛋白质表达增加了一倍。72小时后LIG组中CD36蛋白显著增加。24小时后LIG组和SOP组中SNAT1和SNAT2的蛋白质和基因表达显著降低。进一步显著降低的蛋白质有LIG组(4小时、72小时)和SOP组(24小时)中的GLUT - 1,以及LIG组(72小时)中的连接蛋白26。总之,胎盘营养转运蛋白受血流减少和应激的影响存在差异,可能改变已受干扰的宫内环境,并导致IUGR和胎儿编程。脂肪酸转运能力的增加可能影响能量代谢,并且可能是对脑发育有积极影响的一种代偿反应。《细胞生物化学杂志》117: 1594 - 1603,2016年。© 2015威利期刊公司