Mechanism of Embryo Implantation Promotion via Exosomal miRNA-mediated Communication Network at Maternal-fetal Interface Based on Bushen Huoxue Therapy
10.13422/j.cnki.syfjx.20251314
- VernacularTitle:基于补肾活血法探讨母胎界面外泌体源miRNA介导通信网络促进胚胎着床的机制
- Author:
Pei GUO
1
;
Jiajun LIU
2
;
Hang ZHOU
1
;
Zeyi GUO
2
;
Yili WANG
3
;
Linwen DENG
2
;
Qian ZENG
2
;
Jinzhu HUANG
2
Author Information
1. School of Basic Medical Sciences， Chengdu University of Traditional Chinese Medicine（TCM）， Chengdu 611137， China
2. Hospital of Chengdu University of TCM， Chengdu 610072， China
3. Innovative Institute of Chinese Medicine and Pharmacy/Institute of Interdisciplinary Studies， Chengdu University of TCM， Chengdu 611137， China
- Publication Type:Journal Article
- Keywords:
Bushen Huoxue prescription;
exosome;
miRNA sequencing;
maternal-fetal interface
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2026;32(14):317-327
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate whether Bushen Huoxue prescription improves embryo implantation through regulating exosomal miRNA to enhance maternal-fetal interface communication based on Bushen Huoxue therapy. MethodsIn the animal experiment， all the rats （except for the blank group） were administered hydroxyurea （450 mg·kg-1） via gavage for 10 d， as well as epinephrine （0.3 mg·kg-1） and mifepristone （5.5 mg·kg-1） via subcutaneous injection for 7 d to establish an implantation disorder model of kidney deficiency and blood stasis type. The Bushen Huoxue prescription （BSHX） groups were administered the prescription at different doses （7.30 g·kg-1 for the high-dose group， 3.65 g·kg-1 for the medium-dose group， and 1.83 g·kg-1 for the low-dose group） via gavage. The dydrogesterone group was administered the corresponding medicine （2.63 mg·kg-1） via gavage. After intervention for 10 days， uterine histopathological changes were observed via hematoxylin-eosin （HE） staining. Mucin （MUC1）， forkhead box protein O1 （FoxO1）， and homeobox A10 （HoxA10） expression levels were detected by Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） and Western blot. Cell experiment selected primary endometrial epithelial cells （EEC） and trophoblast cells （TC） as research subjects. Exosome-free medicated serum was prepared by ultracentrifugation and cultured in complete medium. Exosomes were isolated from cell supernatants by ultracentrifugation for cross-co-culture. After 48 h， migration and invasion abilities were assessed by scratch and Transwell assays. Sequencing was then performed on EEC-origin exosomal miRNA. ResultsThe model rats exhibited thin endometrium， along with reduced blood vessels， glandules， and pinopode numbers. BSHX improved endometrial morphology and increased pinopode numbers. MUC1， FoxO1， and HoxA10 expressions were downregulated in the model rats， while these parameters were upregulated after BSHX medium- and high-dose intervention. In the cell experiment， after exosome-free medicated serum intervention for 24 h， migration and invasion abilities were enhanced in the BSHX groups （P<0.01）. In EEC-origin exosomal miRNA sequencing， gene ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） analyses revealed enrichment in biological processes （gastrulation， neuronal differentiation， alongside cell development and regeneration）， involving the mitogen-activated protein kinase （MAPK）， FoxO1， Wnt， mammalian target of rapamycin （mTOR）， and tumor necrosis factor （TNF） signaling pathways. ConclusionBSHX promotes embryo implantation by improving endometrial receptivity via regulating exosomal miRNA. These findings provide potential targets for exosomal miRNA-based assisted reproductive strategies and a novel theoretical basis for infertility treatment by traditional Chinese medicine.
