BMP4 Affects Endometrial Decidualization in RSA Patients by Regulating FOXO1
10.11969/j.issn.1673-548X.2024.10.008
- VernacularTitle:BMP4通过调控FOXO1影响RSA患者子宫内膜蜕膜化
- Author:
Yanjie HUANG
1
;
Fangfang DAI
;
Liping CHEN
Author Information
1. 430060 武汉大学人民医院妇产科
- Keywords:
Recurrent spontaneous abortion;
BMP4;
FOXO1;
Decidualization defect
- From:
Journal of Medical Research
2024;53(10):33-39
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the expression of Bone morphogenetic protein 4(BMP4)in human endometrial stromal cells(hESCs)of patients with recurrent spontaneous abortion(RSA)and the regulation of Forkhead transcription factor 1(FOXO1)by BMP4.Methods The decidua tissues of RSA patients and Healthy control(HC)patients in People's Hospital of Wuhan University were collected,and the expression of BMP4 was analyzed by immunohistochemistry and RT-qPCR.hESC was used in vitro cell experiments,lentivirus was transfected to knock down the expression of BMP4 and establish the cell model of RSA.After decidualization,CCK-8 as-say,inverted microscope,and Western blot assay were used to detect the cell proliferation,morphology,and expression levels of decidual-ization marker genes.To verify whether BMP4 knockdown affects FOXO1 expression,a FOXO1 inhibitor(AS1842856)was used to per-form a response experiment,and the upstream and downstream relationship between FOXO1 and BMP4 was analyzed by CCK-8 experi-ment,inverted microscope,and Western blot.In animal experiments,intraperitoneal injection of LPS-induced abortion in pregnant mice,and the expression of BMP4 in decidua were detected to explore the relationship between BMP4 and abortion in mice.Results Compared with the HC group,the expression of BMP4 in the deciduous tissues of RSA patients was significantly decreased.After BMP4 was knocked down,the decidualization was significantly abnormal,which showed that the proliferation rate increased,the cell morphologi-cal transformation was not obvious,and the expression of decidualization marker genes was down-regulated.FOXO1 was the downstream regulatory molecule of BMP4,knocking down BMP4 could inhibit the expression of FOXO1,and BMP4 could regulate the decidualization of hESC through FOXO1.In animal models,the expression of BMP4 in decidua and placental weight of aborted pregnant mice were signif-icantly reduced.Conclusion The expression of BMP4 was significantly down-regulated in decidual tissues of RSA patients and aborted mice.In cell experiments,BMP4 can promote decidualization of hESC by regulating the expression of FOXO1.Abnormally low expression of BMP4 may be one of the reasons for decidualization defects in RSA patients.
