Laboratoire de Biologie du Stress Oxydant, Département de Biologie Intégrée, Centre Hospitalier Universitaire de Grenoble, Grenoble Cedex 9, France.
J Endocrinol. 2010 Apr;205(1):107-16. doi: 10.1677/JOE-09-0362. Epub 2010 Jan 22.
Early pregnancy is susceptible to oxidative stress, and thus characterisation of antioxidant systems and pro- and anti-apoptotic pathways would improve understanding of placental development and function. We aimed, therefore, to determine the activities of the antioxidant enzymes, copper/zinc-superoxide dismutase (SOD1), manganese-SOD (SOD2), catalase (CAT), glutathione (GSH) peroxidase (GPX) and GSH reductase (GSR); and to quantify the expression of BAX and MCL1 proteins in relation to the developmental changes in antioxidant defences in sheep placentomes sampled on days 35, 55 and 80 of pregnancy. Placentome progesterone content was analyzed to determine steroidogenic capacity. Malondialdehyde (MDA) and protein carbonyl were quantified in placentomes as biomarkers of lipid peroxidation and protein damage respectively. Placentome tissues demonstrated significantly increased content of progesterone and MDA at day 80 of pregnancy and protein carbonyl as early as day 50 of pregnancy. Progesterone and MDA contents were not different between days 35 and 55 of pregnancy. While SOD1 and CAT activities did not alter significantly, SOD2 activity decreased from days 35 to 55. GPX activity increased from days 35 to 55 and increased further to day 80 of pregnancy. GSR activity increased from days 35 to 55 of pregnancy. BAX protein expression decreased, while MCL1 increased from days 35 to 55 and 80 of pregnancy. The increased GPX activity was associated with a decrease in the BAX/MCL1 protein expression ratio. Changes in the antioxidant enzymatic defences could be a part of placentome adaptation to reactive oxygen species-induced oxidative stress at specific early developmental stages of pregnancy.
早期妊娠易受氧化应激影响，因此对抗氧化系统和促凋亡与抗凋亡途径进行特征分析将有助于理解胎盘的发育和功能。因此，本研究旨在确定抗氧化酶（铜锌超氧化物歧化酶[SOD1]、锰超氧化物歧化酶[SOD2]、过氧化氢酶[CAT]、谷胱甘肽过氧化物酶[GPX]和谷胱甘肽还原酶[GSR]）的活性，以及 BAX 和 MCL1 蛋白的表达与妊娠第 35、55 和 80 天绵羊胎盘中抗氧化防御系统发育变化的关系。通过分析胎盘中孕酮含量来确定类固醇生成能力。通过定量分析丙二醛（MDA）和蛋白质羰基，作为脂质过氧化和蛋白质损伤的生物标志物。胎盘中 MDA 和蛋白质羰基的含量在妊娠第 80 天显著增加，而 MDA 的含量在妊娠第 50 天就开始增加。妊娠第 35 天和第 55 天胎盘中孕酮和 MDA 的含量没有差异。SOD1 和 CAT 活性没有显著变化，而 SOD2 活性从妊娠第 35 天到第 55 天下降。GPX 活性从妊娠第 35 天到第 55 天增加，到第 80 天进一步增加。GSR 活性从妊娠第 35 天到第 55 天增加。BAX 蛋白表达减少，而 MCL1 蛋白表达从妊娠第 35 天到第 55 天和第 80 天增加。GPX 活性的增加与 BAX/MCL1 蛋白表达比值的降低有关。抗氧化酶防御系统的变化可能是胎盘中适应妊娠早期特定发育阶段活性氧诱导的氧化应激的一部分。
