Institute of Biodiversity, Animal Health, and Comparative Medicine, College of Medical, Veterinary, and Life Sciences, University of Glasgow, Glasgow G61 1QH, United Kingdom. Peter.O'
J Clin Endocrinol Metab. 2011 Sep;96(9):2851-60. doi: 10.1210/jc.2011-1437. Epub 2011 Jun 29.
Pollutants and toxicants passing from the mother to the fetus may damage developing organ systems. The human fetal liver is both a potential target organ and a critical defense against exposure to such xenochemicals.
The aim of the study was to determine the effects of human fetal toxicant exposure, via maternal smoking, on metabolic enzyme transcripts in the fetal liver.
We conducted an observational study of mRNA transcripts and proteins in livers from second trimester fetuses at the Universities of Aberdeen and Glasgow.
PATIENTS/PARTICIPANTS: Liver samples were taken from 55 normal fetuses from women undergoing second trimester elective termination.
Housekeeping genes for normalization were identified by GeNorm and NormFinder. Levels of mRNA transcripts encoding 15 metabolic enzymes and three xenobiotic receptors were measured. Expression of representative proteins was shown by Western blotting.
Eighty-nine percent of measured transcripts were detectable in the human fetal liver. Eight transcripts showed significant sex-specific differences in expression levels (EPHX1, GSTA1, GSTT1, AHR, AS3MT, GLRX2, GGT1, CAR). In male fetuses, maternal smoking was associated with a decrease in expression of three transcripts (GGT1, CYP2R1, CAR) and an increase in eight transcripts (CYP1A1, EPHX1, NQO1, GSTP1, GSTT1, AHR, AS3MT, GLRX2). In the female, CYP3A7 and EPHX1 were increased in smoke-exposed fetuses.
The human fetal liver expresses a wide array of metabolic enzymes, with sex differences apparent in 44% of the transcripts measured. Exposure of the fetus to pollutants/toxicants is associated with significantly altered transcript expression, with the more marked response in the male potentially affecting levels of endogenous factors involved in fetal growth.
母体传递至胎儿的污染物和有毒物质可能会损害正在发育的器官系统。人类胎儿的肝脏既是潜在的靶器官，也是抵御此类外源性化学物质暴露的关键防御器官。
本研究旨在确定母体吸烟导致的胎儿毒物暴露对胎儿肝脏代谢酶转录本的影响。
我们在阿伯丁大学和格拉斯哥大学进行了一项关于妊娠中期选择性终止妊娠的女性胎儿肝脏中 mRNA 转录本和蛋白质的观察性研究。
患者/参与者：从 55 名接受妊娠中期选择性终止妊娠的女性的正常胎儿中获取肝脏样本。
通过 GeNorm 和 NormFinder 确定内参基因。测量 15 种代谢酶和 3 种外源性化学物质受体编码的 mRNA 转录本的水平。通过 Western 印迹显示代表性蛋白质的表达。
89%的测定转录本可在人类胎儿肝脏中检测到。8 种转录本的表达水平存在显著的性别特异性差异（EPHX1、GSTA1、GSTT1、AHR、AS3MT、GLRX2、GGT1、CAR）。在男性胎儿中，母亲吸烟与三种转录本（GGT1、CYP2R1、CAR）的表达减少和八种转录本（CYP1A1、EPHX1、NQO1、GSTP1、GSTT1、AHR、AS3MT、GLRX2）的表达增加有关。在女性中，暴露于烟雾的胎儿 CYP3A7 和 EPHX1 增加。
人类胎儿肝脏表达广泛的代谢酶，其中 44%的测定转录本存在性别差异。胎儿暴露于污染物/有毒物质与转录本表达的显著改变有关，男性的反应更为明显，可能会影响与胎儿生长有关的内源性因子的水平。
