目的 探究妊娠期维生素D缺乏（vitamin D deficiency,VDD）通过调节PAR1表达,引起胎盘发育不良,最终导致胎儿生长受限的发生机制。方法 根据体质量将4 w龄雌性SD大鼠随机分为两组,每组10只,对照组（Ctrl）饲喂标准饲料,VDD组饲喂维生素D（vitamin D,VD）缺乏饲料。饲喂8 w后与正常雄性SD大鼠进行合笼。妊娠第18 日（gestational day,GD18）时,将两组雌鼠进行麻醉后处死,收集样本,采用ELISA、Western blot检测相关指标。结果 孕前及妊娠GD18时,Ctrl组大鼠的血清25(OH)D浓度分别为（20.37±5.03）ng/ml和（9.09±2.96）ng/ml,VDD组大鼠的血清25(OH)D浓度分别为（13.62±4.55）ng/ml和（5.34±1.63）ng/ml,VDD组大鼠孕前、GD18时血清25(OH)D水平均显著低于Ctrl组（P<0.01或P<0.05）;GD18时,VDD组大鼠孕期体重增长量显著低于Ctrl组（P<0.01）,胎盘组织中VDR、DBP、CYP27B1蛋白表达水平显著下调（P<0.01）,25(OH)D、1,25(OH)2D水平显著降低（P<0.05）,胎盘直径、胎盘重量均显著低于Ctrl组（P<0.01）,胎盘组织MMP2蛋白表达水平显著下调（P<0.05）,而E-cadherin蛋白表达水平显著上调（P<0.05）,胚胎着床数、活胎数、胚胎重量、冠臀长均显著低于Ctrl组（P<0.01）,吸收胎数显著增多（P<0.01）。与Ctrl组相比,VDD组孕鼠胎盘PAR1蛋白表达水平显著下调（P<0.01）。结论 当母体妊娠期VDD时,胎盘PAR1表达水平显著下调,胎盘发育障碍,胎鼠发育迟缓。
Abstract
Objective To explore the mechanism by which maternal vitamin D deficiency during pregnancy impairs placental development and leads to fetal growth restriction by regulating PAR1 expression. Methods Female Sprague-Dawley (SD) rats aged four weeks were randomly allocated into two groups according to their body weight, with 10 rats in each group: the control group (Ctrl), fed a standard diet, and the vitamin D deficiency group (VDD), fed a vitamin D-deficient diet. After 8 weeks of feeding, the rats were mated with normal male SD rats. On day 18 of gestation, both groups of female rats were euthanized under anesthesia, and samples were collected for detection of relevant indicators via ELISA and Western blot analysis. Results Before pregnancy and on gestational day 18 (GD18), the serum 25(OH)D concentrations in the Ctrl group were (20.37 ± 5.03) ng/ml and (9.09 ± 2.96) ng/ml, respectively, while in the VDD group, they were (13.62 ± 4.55) ng/ml and (5.34 ± 1.63) ng/ml, respectively. The serum 25(OH)D levels in the VDD group were significantly lower than those in the Ctrl group both before pregnancy and on GD18 (P<0.01 or P<0.05). On GD18, the weight gain during pregnancy in the VDD group was significantly lower than that in the Ctrl group (P<0.01). Compared to the Ctrl group, the protein expression levels of VDR, DBP, and CYP27B1 in the placental tissue of the VDD group were significantly downregulated (P<0.01), and the levels of 25(OH)D and 1,25(OH)2D were significantly reduced (P<0.05). The placental diameter and weight in the VDD group were significantly lower than those in the Ctrl group (P<0.01). The expression levelof MMP2 protein was significantly downregulated (P<0.05), while the expression level of E-cadherin protein was significantly upregulated (P<0.05). The number of embryo implantations, live fetuses, embryo weight, and crown-rump length in the VDD group were significantly lower than those in the Ctrl group (P<0.01), and the number of resorbed fetuses was significantly increased (P<0.01). Compared to the Ctrl group, the expression level of PAR1 protein in the placenta of the VDD group was significantly downregulated (P<0.01). Conclusion Maternal vitamin D deficiency during gestation significantly downregulates placental PAR1 expression, leading to placental developmental disorders and fetal growth retardation.
关键词
维生素D（VD） /
PAR1 /
胎盘发育 /
宫内生长受限
Key words
vitamin D (VD) /
PAR1 /
placental development /
intrauterine growth restriction
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基金
山西省回国留学人员科研资助项目（No.2022-114）; 山西省基础研究计划项目（No.202203021211227）
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