INHIBITION OF HIPPO-YAP SIGNALING PATHWAY IS EFFECTIVE IN IMPROVING ADVERSE PREGNANCY OUTCOMES CAUSED BY VITAMIN D DEFICIENCY IN RATS
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.[ACTA NUTRIMENTA SINICA,2024,46(1):34-39]
vitamin DHippo signaling pathwaypregnancy outcomeplacental development
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