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Potential Mechanism of Bushen Tiaojing Fang on Development of Blastocysts in Mice Induced by Repeated Controlled Ovarian Hyperstimulation: Comprehensive Evidence from Network Pharmacology, Molecular Docking and Experimental Validation

Year: 2025
Type: article
Abstract: Objective In vitro fertilization-embryo transfer (IVF-ET) is a primary treatment method for infertility. It usually requires controlled ovarian hyperstimulation (COH) or repeated COH to obtain more superior oocytes, which could impair ovarian function, reduce embryo quality and limit pregnancy rates. Bushen Tiaojing Fang (BSTJF), our clinically effective prescription for kidney deficiency-related infertility over four decades, while its potential mechanisms to improve pregnancy rates and embryo quality remain unclear. Methods In this study, we focus on the approach of network pharmacology to predict key compounds, core targets, and potential mechanisms of BSTJF for blastocyst induced by repeated COH, mainly including drug-likeness (DL) and oral bioavailability (OB) screening, “herb-component-target-blastocyst” (HCTB) and protein-protein interaction (PPI) networks construction and analysis, GO and KEGG enrichment annotation, molecular docking and basic experiments validation. Results Network pharmacology analysis identified 29 key targets of BSTJF associated with blastocyst development. GO and KEGG enrichment revealed the key targets mainly involved regulating apoptosis to modulate the cell cycle, and demonstrated significant involvement in Cancer, PI3K-Akt, and HIF-1 signaling pathways. In vivo experiments suggested that BSTJF effectively improved the pregnancy rate of repeated COH mice, increased the number of blastocysts while enhancing the rate of high-quality blastocysts. Immunofluorescence (IF) results showed a significant downregulation of P21 and Bax proteins, and a significant upregulation of Cyclin B1 and Bcl-2 proteins in blastocyst of mice treated with BSTJF. Conclusion The study revealed the potential mechanism by which BSTJF could boost embryo quality in mice with repeated COH via activating the PI3K-Akt signaling pathway, which balances the proliferation and apoptosis of blastocyst cells, ultimately restoring normal cell cycle progression and offering new therapeutic strategies for IVF-ET.
Authors: Beibei Shi, Lulu Shen, Wenyan Xiong, Yajing Song, Ruigan Shi, Huilan Du
Language: English
Field: Medicine
Open Access status: gold
Estimated APC paid: $2,650
OpenAlex ID: W4414911384
FWCI:
Cites: 52
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