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首页> 外文期刊>The Journal of Nutritional Biochemistry >Supplementation with high-dose cholecalciferol throughout pregnancy induces fetal growth restriction through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition
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Supplementation with high-dose cholecalciferol throughout pregnancy induces fetal growth restriction through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition

机译：通过抑制胎盘增殖和滋养细胞上皮 - 间充质转换，在妊娠中补充具有高剂量胆碱基溶胶诱导胎儿生长限制

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摘要

Vitamin D deficiency has been associated with adverse pregnant outcomes. Several studies investigated the effects of maternal vitamin D3 supplementation on fetal development with inconsistent results. The aim of this study was to investigate the effects of maternal supplementation with different doses of vitamin D3 on fetal development. Pregnant mice were administered with different doses of cholecalciferol (0, 2,0 0 0, 10,0 0 0, 40,0 0 0 IU/kg/day) by gavage throughout pregnancy. Fetal weight and crown-rump length were measured. Placental proliferation and mesenchymal characteristics were detected. HTR-8/SVneo cells were incubated in the absence or presence of calcitriol (500 nmol/L) to evaluate the effects of active vitamin D3 on migration and invasion of human trophoblast cells. Although a low dose of cholecalciferol was safe, fetal weight and crown-rump length were decreased in dams treated with high-dose cholecalciferol throughout pregnancy. Placental weight and labyrinth thickness were reduced in mice administered with high-dose cholecalciferol. An obvious calcification was observed in placentae of mice administered with high-dose cholecalciferol. Ki67-positive cells, a marker of placental proliferation, were reduced in mice administered with high-dose cholecalciferol. N-cadherin and vimentin, two mesenchymal markers, were decreased in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. MMP-2 and MMP-9, two matrix metalloproteinases, were down regulated in cholecalciferol-treated mouse placentae and calcitriol-treated human trophoblast cells. In addition, trophoblast migration and invasion were suppressed by calcitriol. Supplementation with high-dose cholecalciferol induces fetal growth restriction partially through inhibiting placental proliferation and trophoblast epithelial-mesenchymal transition. ? 2021 Elsevier Inc. All rights reserved.
机译：维生素D缺乏与不良妊娠结局有关。一些研究调查了母亲补充维生素D3对胎儿发育的影响，但结果不一致。本研究的目的是研究母亲补充不同剂量的维生素D3对胎儿发育的影响。妊娠小鼠在整个妊娠期间通过灌胃给予不同剂量的胆钙化醇（0,2,0,10,0,40,0 IU/kg/天）。测量胎儿体重和冠臀长度。检测胎盘增殖和间充质特征。HTR-8/SVneo细胞在不存在或存在骨化三醇（500 nmol/L）的情况下培养，以评估活性维生素D3对人类滋养层细胞迁移和侵袭的影响。尽管低剂量的胆钙化醇是安全的，但在整个妊娠期间，高剂量的胆钙化醇治疗的母鼠的胎儿重量和冠臀长度都减少了。服用高剂量胆钙化醇的小鼠胎盘重量和迷路厚度降低。在服用高剂量胆钙化醇的小鼠的胎盘中观察到明显的钙化。Ki67阳性细胞是胎盘增殖的标志，在服用高剂量胆钙化醇的小鼠中减少。在胆钙化醇处理的小鼠胎盘和骨化三醇处理的人类滋养层细胞中，两种间充质标记物N-钙粘蛋白和波形蛋白降低。两种基质金属蛋白酶MMP-2和MMP-9在胆钙化醇处理的小鼠胎盘和骨化三醇处理的人类滋养层细胞中表达下调。此外，骨化三醇抑制了滋养层细胞的迁移和侵袭。补充高剂量胆钙化醇部分通过抑制胎盘增殖和滋养层上皮间质转化诱导胎儿生长受限？2021爱思唯尔公司保留所有权利。

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