Brant Kelly A, Caruso Rita Loch
Department of Environmental Health Sciences, University of Michigan, Ann Arbor, MI 48109-2029, USA.
Reprod Toxicol. 2006 Nov;22(4):591-8. doi: 10.1016/j.reprotox.2006.04.012. Epub 2006 May 19.
Amniotic phospholipase A2 activity contributes to elevated levels of arachidonic acid and prostaglandins observed during labor. Polychlorinated biphenyls (PCBs) activate PLA2 and have been associated with shortened gestation length. To determine if PCBs stimulate amniotic PLA2, cell cultures of rat amnion fibroblasts (RAF) were established from gestation day (gd) 20 rats and labeled with 0.5 micro Ci [3H]-arachidonic acid prior to a 0.5- or 4-h exposure to 0.1% DMSO (solvent control), PCB 50 (1-50 micro M) or TNFalpha (positive control). PCB 50 and TNFalpha induced significant release of [3H]-arachidonic acid from amnion fibroblast cells in time-dependent manners (p<0.001), an effect associated with a significant increase in iPLA2 expression (p<0.05). PCB 50 also stimulated prostaglandin production from RAF cells independent of changes in immunoreactive COX-2. These data suggest that amnion may serve as a target for PCB-induced release of arachidonic acid and uterotonic prostaglandins, with a potential for adverse pregnancy outcomes.
羊膜磷脂酶A2活性导致分娩期间观察到的花生四烯酸和前列腺素水平升高。多氯联苯(PCBs)可激活磷脂酶A2,并与缩短妊娠期有关。为了确定多氯联苯是否刺激羊膜磷脂酶A2,从妊娠第20天的大鼠建立大鼠羊膜成纤维细胞(RAF)细胞培养物,并在暴露于0.1%二甲基亚砜(溶剂对照)、多氯联苯50(1-50微摩尔)或肿瘤坏死因子α(阳性对照)0.5小时或4小时之前,用0.5微居里[3H] -花生四烯酸进行标记。多氯联苯50和肿瘤坏死因子α以时间依赖性方式诱导羊膜成纤维细胞中[3H] -花生四烯酸的显著释放(p<0.001),这一效应与iPLA2表达的显著增加相关(p<0.05)。多氯联苯50还刺激RAF细胞产生前列腺素,而与免疫反应性COX-2的变化无关。这些数据表明,羊膜可能是多氯联苯诱导花生四烯酸和子宫收缩性前列腺素释放的靶点,具有导致不良妊娠结局的可能性。