Dose effect of gestational ethanol exposure on placentation and fetal growth.
Dose effect of gestational ethanol exposure on placentation and fetal growth.
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DOI：
10.1016/j.placenta.2015.02.010
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发表时间：
2015-05
期刊：
影响因子：
3.8
通讯作者：
de la Monte, S. M.
中科院分区：
文献类型：
--
作者：
Gundogan, F.;Gilligan, J.;Qi, W.;Chen, E.;Naram, R.;de la Monte, S. M.
关键词：
产前酒精暴露通过损害胎盘形成损害胎儿生长。介导胎盘形成的侵袭性滋养层细胞表达胰岛素-IGF调节的基因-天冬酰胺酰β-羟化酶（ASPH），其在细胞运动和侵袭中具有关键作用。本研究的目的是描述乙醇对滋养层细胞运动的影响，并评估乙醇对胎盘形成和胎儿发育的剂量依赖性损害。从妊娠第6天（GD）至GD 18天，用含0%、8%、18%或37%乙醇（热量含量）的等热量流质饲料喂养妊娠Long Evans母鼠。评估胎儿发育、胎盘形态、子宫系膜三角区浸润性滋养细胞密度以及胎盘和子宫系膜ASPH和Notch-1蛋白表达。通过基于ATP发光的测定评估对照和乙醇暴露的HTR-8/SVneo细胞的定向运动性。胎儿生长障碍的严重程度与乙醇剂量的增加相关。乙醇暴露产生剂量依赖性的改变，在分支形态发生在胸腺区，并抑制母体动脉的生理转化。ASPH和Notch-1蛋白表达水平降低，与胎盘形成障碍相对应。产前乙醇暴露以剂量反应方式损害胎儿生长和胎盘形成。乙醇对胎盘发育的不利影响是通过以下方式介导的：1）胎盘带中分支形态发生的改变; 2）侵袭性滋养层前体细胞的抑制;以及3）滋养层细胞粘附和运动的抑制，与ASPH和Notch-1蛋白表达的降低相对应。
Prenatal ethanol exposure compromises fetal growth by impairing placentation. Invasive trophoblastic cells, which mediate placentation, express the insulin-IGF regulated gene, aspartyl-asparaginyl β-hydroxylase (ASPH), which has a critical role in cell motility and invasion. The aims of this study were to characterize effects of ethanol on trophoblastic cell motility, and assess ethanol dose -dependent impairments in placentation and fetal development. Pregnant Long Evans dams were fed with isocaloric liquid diets containing 0%, 8%, 18% or 37% ethanol (caloric content) from gestation day (GD) 6 to GD18. Fetal development, placental morphology, density of invasive trophoblasts at the mesometrial triangle, as well as placental and mesometrial ASPH and Notch-1 protein expression were evaluated. Directional motility of control and ethanol-exposed HTR-8/SVneo cells was assessed by ATP Luminescence-Based assay. Severity of fetal growth impairment correlated with increasing doses of ethanol. Ethanol exposure produced dose-dependent alterations in branching morphogenesis at the labyrinthine zone, and inhibited physiological transformation of maternal arteries. ASPH and Notch-1 protein expression levels were reduced, corresponding with impairments in placentation. Prenatal ethanol exposure compromises fetal growth and placentation in a dose-responsive manner. Ethanol’s adverse effects on placental development are mediated by: 1) altered branching morphogenesis in labyrinthine zone; 2) suppression of invasive trophoblastic precursor cells; and 3) inhibition of trophoblastic cell adhesion and motility, corresponding with reduced ASPH and Notch-1 protein expression.
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