目的 探讨抑制Hippo-YAP信号通路的激活是否能改善维生素D缺乏（vitamin D deficiency,VDD）所导致的胎盘及胚胎发育不良。方法 按照体质量将4w龄SD雌性大鼠随机分为对照组（Ctrl）、VD 缺乏组（VDD）、VD缺乏阴性对照组（VDD+vehicle）与VD缺乏抑制剂组（VDD+XMU-MP-1）,Ctrl组采用标准饲料喂养,VDD组采用VD缺乏饲料喂养,喂养8 w后雌雄合笼。VDD+vehicle组与VDD+XMU-MP-1组在妊娠0-10 d（GD 0-10）进行腹腔注射。结果 VD缺乏8 w后,与Ctrl组相比,VDD组血清25（OH）D水平均降低,且Ctrl组与VDD组、VDD+vehicle组间差异均有统计学差异（P<0.05）;GD18时,与Ctrl组相比,VDD组血清25（OH）D水平略有降低。GD18时,与Ctrl组相比,VDD组、VDD+vehicle组（P<0.01）及VDD+XMU-MP-1组（P<0.01）胎盘25（OH）D水平均降低;与Ctrl组相比,其他三组胎盘1,25（OH）2D水平均有所降低,且Ctrl组与VDD+vehicle组、VDD+XMU-MP-1组均有统计学差异（P<0.01）。与Ctrl组相比,VDD组胎盘（P<0.01）、胚胎（P<0.05）重量明显下降,与VDD+vehicle组相比,VDD+XMU-MP-1组胎盘重量有所增加,组间有统计学差异（P<0.05）,而胚胎重量略有增加;与Ctrl组相比,VDD组胎盘直径、胚胎冠臀长明显降低,且均有统计学差异（P<0.01）,与VDD+vehicle组相比,VDD+XMU-MP-1组胎盘直径（P<0.05）、胚胎冠臀长（P<0.01）有所增加。结论 维生素D缺乏对胚胎发育的损害作用涉及胎盘组织Hippo-YAP通路的激活,Hippo-YAP信号通路可能是预防维生素D缺乏所致不良妊娠结局的潜在靶点。
Abstract
Objective To investigate whether inhibition of Hippo-Yap signaling pathway can improve placental and embryonic dysplasia caused by vitamin D deficiency(VDD). Methods Based on body weight, female SD rats aged 4 weeks were randomly divided into control group (Ctrl), VDD group, VDD negative control group (VDD+vehicle), and VDD inhibitor group (VDD+XMU-MP-1). The Ctrl group was fed a standard diet, and the VDD group was fed a VD deficient diet. After 8 weeks of feeding, male and female rats were mated. The VDD+vehicle group and the VDD+XMU-MP-1 group received intraperitoned injection of vehicle or XMU-MP-1 at 0-10d of gestation (GD0-10). Results After 8w of VD deficiency, serum 25(OH)D levels in the VDD group were decreased compared with the Ctrl group, and there were statistical differences between the three groups (P<0.05). On GD18, serum 25(OH)D levels were slightly lower in the VDD group than in the Ctrl group. On GD18, compared with the Ctrl group, the levels of placenta 25(OH)D in the VDD group, VDD+vehicle group (P<0.01) and VDD+XMU-MP-1 group (P<0.01) were decreased. Compared with the Ctrl group, the placental 1,25(OH)2D levels in the other three groups were decreased, and there was a statistical difference between the Ctrl group and the VDD+vehicle group, VDD+XMU-MP-1 group (P<0.01). Compared with the Ctrl group, the weights of placenta (P<0.01) and embryo (P<0.05) in the VDD group decreased significantly. Compared with the VDD+vehicle group, the weight of placenta in the VDD+XMU-MP-1 group increased, with statistical difference between two groups (P<0.05), while the weight of embryo increased slightly. Compared with the Ctrl group, the placental diameter and fetal crown hip length in the VDD group were significantly decreased, with statistical differences (P<0.01). Compared with the VDD+vehicle group, the placental diameter (P<0.05) and fetal crown hip length in the VDD+XMU-MP-1 group were increased (P < 0.01). Conclusion The damaging effect of VDD on fetal development involves the activation of Hippo-Yap pathway in placental tissue, which may be a potential target for preventing adverse pregnancy outcomes caused by VDD.
关键词
维生素D（VD） /
Hippo-YAP信号通路 /
妊娠结局 /
胎盘发育
Key words
vitamin D /
Hippo signaling pathway /
pregnancy outcome /
placental development
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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）
