Department of Tropical Medicine, Medical Microbiology and Pharmacology, John A. Burns School of Medicine, University of Hawaii, Biosciences 320, 651 Ilalo St, Honolulu, HI 96813, USA.
Placenta. 2011 Nov;32(11):852-8. doi: 10.1016/j.placenta.2011.08.003. Epub 2011 Sep 1.
Higher rates of low birth weight and prematurity are observed in pregnancies generated with assisted reproduction technologies (ART). Both conditions have been associated with placental inflammation and oxidative stress. Since placental and fetal levels of progesterone, a major anti-inflammatory steroid, are decreased in murine ART, we investigated placental inflammation and oxidative stress in this model as potential mediators of negative birth outcomes. After generating mouse pregnancies by in vitro fertilization (IVF) and intracytoplasmic sperm injection (ICSI) we evaluated the antioxidant defense network and major inflammatory cytokines in maternal, placental and fetal tissues. Additionally, placentas were analyzed for total lipid levels, fibrosis, apoptosis, reactive oxygen species and integrity of intracellular nucleotides. Placentas from ART contained significantly less lipids, with greater levels of apoptosis and degraded nucleotides. Placentas from ICSI pregnancies had lower activities of superoxide dismutase (SOD), thioredoxin reductase (TrxR), xanthine oxidase (XO), catalase, glutathione-S-transferase (GST) glutathione peroxidase, and glutathione reductase (GR). Furthermore, GR, GST and SOD were also lower in fetal livers from ICSI pregnancies. Placentas from IVF pregnancies had decreased levels of SOD, TrxR and XO only. In placentas from both ICSI and IVF pregnancies IL-6 levels were significantly increased. These data suggest that ART is associated with placental inflammation (IL-6), oxidative stress and apoptosis but not fibrosis or remodeling. These effects are markedly greater with the ICSI technique. Since ICSI is ubiquitous, oxidative stress and placental inflammation associated with this method may be a critical factor in negative birth outcomes such as prematurity and low birth weight.
辅助生殖技术（ART）产生的妊娠中，低出生体重和早产的发生率较高。这两种情况都与胎盘炎症和氧化应激有关。由于鼠类 ART 中胎盘和胎儿的孕激素（一种主要的抗炎类固醇）水平降低，我们研究了这种模型中的胎盘炎症和氧化应激，作为不良出生结局的潜在介导因素。通过体外受精（IVF）和胞浆内精子注射（ICSI）产生小鼠妊娠后，我们评估了母体、胎盘和胎儿组织中的抗氧化防御网络和主要炎症细胞因子。此外，还分析了胎盘的总脂质水平、纤维化、细胞凋亡、活性氧和细胞内核苷酸的完整性。ART 胎盘的脂质含量明显较少，细胞凋亡和降解核苷酸的水平更高。ICSI 妊娠的胎盘中超氧化物歧化酶（SOD）、硫氧还蛋白还原酶（TrxR）、黄嘌呤氧化酶（XO）、过氧化氢酶、谷胱甘肽-S-转移酶（GST）和谷胱甘肽还原酶（GR）的活性较低。此外，ICSI 妊娠胎儿肝脏中的 GR、GST 和 SOD 也较低。IVF 妊娠的胎盘仅 SOD、TrxR 和 XO 水平降低。ICSI 和 IVF 妊娠的胎盘中 IL-6 水平均显著升高。这些数据表明，ART 与胎盘炎症（IL-6）、氧化应激和细胞凋亡有关，但与纤维化或重塑无关。ICSI 技术的这些影响更为显著。由于 ICSI 技术无处不在，与该方法相关的氧化应激和胎盘炎症可能是早产和低出生体重等不良出生结局的关键因素。
