Imbalance Mechanism of Autophagy and Apoptosis in Placental Trophoblasts of Puerperae with Fetal Growth Restriction

ZHANG Yuling; GAO Shanshan; ZHANG Hongli; LI Qinqin; CAI Dajun

doi:10.3969/j.issn.1004-437X.2026.12.002

Abstract：Objective To investigate the regulatory mechanism of placental trophoblast autophagy and apoptosis in fetal growth restriction(FGR).Methods Placental tissues from 30 pregnant women who delivered with FGR at the Second Affiliated Hospital of Zhengzhou University from January to December 2024 were selected as the FGR group,and placental tissues from 30 pregnant women with normal delivery during the same period were enrolled as the healthy control group.Clinical data of both groups were collected.The mRNA expression levels of BAX,BCL2,ATG7,CAPN1,Beclin1,and ATG3 in placental villus tissues were detected by qRT-PCR.The protein levels of BAX,BCL2,cleaved CASP3,cleaved CASP8,p62/SQSTM1,and CAPN1 were measured by ELISA.The differences between the two groups and the correlations among indicators were analyzed.Results Apoptosis-related indicators:compared with the healthy group,the expression of anti-apoptotic BCL2(both gene and protein)was decreased in the FGR group,while the levels of pro-apoptotic BAX,cleaved CASP3,and cleaved CASP8 were increased,accompanied by an elevated BAX/BCL2 protein ratio(P＜0.05).Autophagy-related indicators:the mRNA expression of the key autophagy gene ATG7 was reduced(P＜0.05),and the level of autophagy substrate protein p62/SQSTM1 was increased(P＜0.05)in the FGR group.In addition,the protein level of calpain CAPN1 was elevated(P＜0.05)and showed a positive correlation with p62 protein level(r=0.504,P＜0.001).The p62 protein level was negatively correlated with neonatal birth weight(r=-0.420,P=0.006).Conclusion Impaired autophagy(mediated by downregulated ATG7 and upregulated CAPN1)and increased apoptosis(induced by BAX/BCL2 imbalance)in placental trophoblasts are jointly involved in the pathogenesis of FGR.The accumulation of p62 is negatively correlated with fetal birth weight,which may affect fetal growth and development.