背景:高龄(AMA)女性的生育增加了对人工生殖技术(ART)的需求。ART和氧化应激与许多妊娠并发症有关。对氧磷酶(PON)1是负责高密度脂蛋白(HDL)抗氧化活性的关键成分之一。本研究旨在探讨接受ART的老年女性氧化应激和PON1内酰胺酶活性及状态的纵向变化。
方法:这项前瞻性巢式病例对照研究包括129名对照和64名ART女性。分别在妊娠的不同阶段采集血样。使用7-O-二乙基磷酰基-3-氰基-4-甲基-7-羟基香豆素(DEPCyMC)和5-硫代丁基丁内酯(TBBL)作为底物,评估了PON1水平和内酯活性,分别。基于TBBLase与DEPCyMCase活性的比率来估计标准化的内酯酶活性(NLA)。血清总氧化剂状态(TOS),总抗氧化能力(TAC),丙二醛(MDA),同型半胱氨酸(HCY),PON1C-108T和Q192R基因多态性,并对代谢参数进行分析。
结果:内酰胺酶活性和PON1水平随妊娠进展而逐渐降低,而糖脂代谢参数和TAC水平随着妊娠进展而增加或在第2和第3个月期间显着增加,和PON1的NLA,TOS,OSI,MDA,ART组和对照组分娩前HCY显著增加。与对照女性相比,ART妇女在怀孕期间具有较高或相对较高的内酰胺酶活性和PON1和TAC的NLA;较高的甘油三酯(TG),总胆固醇,低密度脂蛋白胆固醇,致动脉粥样硬化指数,载脂蛋白(载脂蛋白)B,和apoB/apoA1比率在妊娠早期;和较高的空腹血糖,空腹胰岛素,胰岛素抵抗的稳态模型评估,和TG水平在交货前。ART组和对照组之间的PON1C-108T和Q192R基因型和等位基因频率没有显着差异。
结论:接受ART的AMA女性有更高的TAC,PON1内酰胺酶活性,和PON1NLA比对照女性,表明ART女性的补偿性抗氧化能力增加,因此对氧化应激相关的损伤和疾病表现出更高的敏感性。
BACKGROUND: Childbearing in women with advanced maternal age (AMA) has increased the need for artificial reproductive technology (ART). ART and oxidative stress are associated with many pregnancy complications. Paraoxonase (PON) 1 is one of the key components responsible for antioxidative activity in high-density lipoprotein (HDL). This study aimed to investigate the longitudinal changes of oxidative stress and PON1 lactonase activity and status in older women undergoing ART.
METHODS: This prospective nested
case-control study included 129 control and 64 ART women. Blood samples were obtained respectively at different stages of pregnancy. PON1 level and lactonase activity were assessed using 7-O-diethylphosphoryl-3-cyano-4-methyl-7-hydroxycoumarin (DEPCyMC) and 5-thiobutyl butyrolactone (TBBL) as a substrate, respectively. A normalized lactonase activity (NLA) was estimated based on the ratio of TBBLase to DEPCyMCase activity. Serum total oxidant status (TOS), total antioxidant capacity (TAC), malondialdehyde (MDA), homocysteine (HCY), PON1 C-108T and Q192R genetic polymorphisms, and metabolic parameters were analyzed.
RESULTS: Lactonase activity and level of PON1 gradually decreased with pregnancy progression, while glycolipid metabolism parameters and TAC levels increased with pregnancy progression or significantly raised during the 2nd and 3rd trimesters, and NLA of PON1, TOS, OSI, MDA, and HCY significantly increased before delivery in the ART and control groups. Compared with the control women, the ART women had substantially higher or relatively high lactonase activity and NLA of PON1 and TAC during pregnancy; higher triglyceride (TG), total cholesterol, low-density lipoprotein cholesterol, atherogenic index, apolipoprotein (apo) B, and apoB/apoA1 ratio in the 1st trimester; and higher fasting glucose, fasting insulin, homeostatic model assessment of insulin resistance, and TG levels before delivery. No significant differences were found in the frequencies of PON1 C-108T and Q192R genotypes and alleles between the ART and control groups.
CONCLUSIONS: Women with AMA undergoing ART had higher TAC, PON1 lactonase activity, and PON1 NLA than control women, suggesting increased compensatory antioxidant capacity in ART women, thus showing higher sensitivity to oxidative stress-related injury and diseases.