Expression Of The HIF-VEGF-Notch Signaling Pathway-related Factors In Placenta Of Clubfoot-like Fetus Pregnant Rat

OBJECTIVE:To investigate the expression of the HIF-VEGF-Notch signaling pathway-related factors in the placenta of clubfoot-like fetus pregnant rats in duced by all-trans-retinoic acid(ATRA) under the method of making rats club foot-like models in order to provide new ideas for clinical treatment in study the causes of CCF.METHODS:Twenty pregnant SD rats equally randomized into two groups of A(intragastric administration of ATRA)and B(normal controls).120 mg/kg ATRA dissolved in mineral oil was given intragastrically to the rats in the experimental group of pregnancy on the 10th day. And equivalent volume of mineral oil was given intragastrically to the control rats. The rats in experimental group and control group were fed with ordinary water and food. The placenta tissues were taken on the 20th day of pregnancy,and the mRNA and protein expressions of HIF-1,VEGF,and Notch 1 were detected by RT-PCR and Western blot,respectively.RESULTS:122 fetus rats were takern in the control group of 10 pregnant rats,no deformity.One pregnant rat dead after two days’.78 fetus rats were takern by remaining nine pregnant rats,and there were 42 fetus rats have the deformity of CCF, the probability of CCF was 52.8%.Compared with group B,the mRNA and protein expressions of VEGF were deceased,which of HIF-1 and Notch1 were observably increased in group A(p<0.05).CONCLUSION:Abnormal apoptosis of cells were detected in the placenta of clubfoot-like fetus pregnant rats induced by ATRA.At the same time,the reduce of placental weight and the decreases of vascular number, the thick vessel wall,partly occlusion of the vascular and capillary increased in number and length were observed, witch affect the blood supply of placenta. HIF-VEGF-Notch signaling pathway played an important role in regulation of angiogenesis by promoting the proliferation, migration, arteriovenous differentiation of vascular endothelial cells.Great changes were detected in thethe placenta of clubfoot-like fetus pregnant rats about HIF-VEGF-Notch signaling pathways related factors,witch suggests that HIF-VEGF-Notch signaling pathway-related factors may be associated with congenital clubfoot.