Study On Expression Of Apoptosis - Related Genes In Placenta Tissue Of Pregnant Rats With Foot - Induced Foothopper Induced Fold

Objective:To investigate the apoptotic gene expression in lower limb of all-trans-retinoic acid (ATRA) induced congenital clubfoot fetus rat model and placenta in fetus congenital clubfoot pregnant rat model.Methods:Sprague-Dawley (SD) rats were randomly divided into experimental group and control group. On day 10 of pregnancy, a dose of 120mg/kg ATRA dissolved in mineral oil was given to the rats in the experimental group intragastrically and equivalent volume of mineral oil was given to the control rats. Embryos were delivered on day 20 of pregnancy, and lower limb and placenta were collected for biochemical and pathological analysis.Results:Malformation fetuses were observed in the experimental group included clubfoot-like deformity, craniofacial abnormality, absent or deformed tail and neural tube defect, however, none with deformity was found in the control group. Compared with the control group, in the lower limb, the lower expression of Bcl-2 and higher expression of BAX were found in the experimental group in both mRNA and protein level. The caspase-3 activity was significantly increased in the experimental group than control group in lower limb. The pro-apoptosis in placenta of ATRA-exposed group was measured by flow cytometry. Moreover, compared with the control group, lower expression of Bcl-2 and higher expression of BAX were found in the ATRA-exposed group in both mRNA and protein level. Immunohistochemical labeling of Bcl-2 in the control group was more intense while BAX labeling in the ATRA-exposed group was more intense. Additionally, the caspase-3 activity was also significantly increased in the ATRA-exposed group than control group. Conclusion:In our research, we found an unbalanced apoptosis in lower limb in the ATRA induced clubfoot like fetus, indicating a possible association between apoptosis in lower limb tissue and congenital clubfoot. We also found a pro-apoptosis in placenta in the ATRA-exposed pregnant rats, which also indicating a possible association between placental apoptosis and congenital clubfoot.