母体孕期维生素D缺乏对胎盘甾体激素合成的影响

The effect of maternal vitamin D deficiency on placental steroid hormone synthesis during pregnancy

目的探讨母体孕期维生素D缺乏(VDD)诱发胎儿宫内生长受限(IUGR)的机制。方法4周龄雌性CD-1小鼠随机分成2组:对照组(CTRL组)和维生素D缺乏组(VDD组),低维生素D饲料喂养5周构建VDD动物模型,然后与正常雄鼠交配,在孕第16天剖杀部分孕鼠,收集胎盘、母血以及胎血,Western blot法检测胎盘甾体激素合成关键酶以及氧化应激信号蛋白表达水平,用放射免疫分析法检测母血雌激素、孕激素和25-(OH)-D水平;在孕第19天剖杀剩余孕鼠,称量胎盘和胎鼠重量,测量胎鼠身长和胎盘直径,观察妊娠结局。结果5周低维生素D饲料喂养成功构建VDD小鼠模型;母体孕期维生素D缺乏减轻胎鼠重和胎盘重量,降低胎鼠身长和胎盘直径。VDD组胎盘芳香化酶P450(CYP19)表达升高,孕鼠雌激素合成增多。此外,维生素D缺乏上调胎盘血红素加氧酶-1(HO-1)、NADPH氧化酶-4(NOX-4)和3-硝基酪氨酸(3-NT)蛋白表达水平,促进了胎盘核因子E-2相关因子2(Nrf-2)核转位水平。结论母体孕期维生素D缺乏可能部分通过诱发胎盘氧化应激损伤胎盘内分泌功能,促进胎盘雌激素合成进而诱发IUGR。

Objective To explore the mechanism of maternal vitamin D deficiency(VDD)-induced fetal intrau-terine growth restriction(IUGR)during pregnancy.Methods Four weeks female CD-1 mice were divided into two groups:control mice(CTRL)and vitamin D deficiency mice(VDD).VDD mice were fed with diet with low concentration of vitamin D and mated with normal male mice.Several pregnant mice were killed on gestational sixteenth day,and the placentas,serum of maternal and fetal mice were collected.Proteins of placental key enzymes of steroid hormone synthesis and signaling pathways of oxidative stress were measured using Western blot.Serum estrogen,progesterone and 25-(OH)-D were measured via radioimmunoassay.The remaining pregnant mice were killed.Placentas and fetus were weighted,fetus height and placental diameter were calculated.The pregnancy outcomes were observed.Results Diet with low concentration of vitamin D were used and VDD mice model were established after five weeks.Maternal VDD during pregnancy decreased the weight of placenta and fetus,reduced the height of fetus and the diameter of placentas.The expression of placental aromatase cytochrome p450(CYP19)and the level of estrogen were increased in VDD pregnant mice.Besides,maternal VDD during pregnancy increased the expressions of placental heme oxygenase 1(HO-1),NADPH oxidase 4(NOX-4)and 3-nitrotyrosine(3-NT).VDD promoted placental nuclear factor E2-related factor 2(Nrf-2)nuclear translocation.Conclusion Maternal vitamin D deficiency during pregnancy causes IUGR partially through evoking placental oxidative stress and promoting estrogen synthesis.