Jiawei Shoutai Pill Promotes Embryo Implantation via PPAR Signaling and Endometrial Microbiota Remodeling: An Integrative Multi-Omics Study

ABSTRACT: Background: Recurrent implantation failure (RIF) remains a major barrier to successful assisted reproductive technology, given the lack of effective, mechanism-informed interventions to enhance endometrial receptivity. Jiawei Shoutai Wan (pills) (JWSTW), a modified formulation of the classic Shoutai Pill (STP) used in reproductive medicine, has not been systematically evaluated in the treatment of RIF, and its bioactive components and molecular targets remain largely unclear. Purpose: To determine whether JWSTW improves implantation competence and to identify the pathways associated with its effects. Materials and methods: A mifepristone-induced embryo implantation dysfunction (EID) rat model was established to evaluate implantation outcomes, uterine histology, and markers of endometrial receptivity and vascular perfusion. Bulk uterine transcriptomics and peripheral blood serum untargeted metabolomics were integrated with liquid chromatography-tandem mass spectrometry (LC-MS) based component profiling, network pharmacology, multi-omics correlation analysis, uterine cavity microbiota profiling and structure-based computational analyses. Key pathway molecules were further assessed using targeted molecular experiments. A retrospective cohort of RIF patients undergoing assisted reproduction was analyzed for ultrasound-derived endometrial receptivity parameters before and after treatment. Results: JWSTW administration improved implantation outcomes in EID rats, characterized by the upregulation of multiple receptivity- and perfusion-associated tissue markers. Integrated multi-omics analyses identified peroxisome proliferator-activated receptor (PPAR) signaling and lipid metabolism as significantly enriched pathways, supported by corresponding gene-metabolite correlations. JWSTW was also associated with structured changes in the uterine cavity microbiota, with enriched taxa and predicted functions aligned with lipid metabolism related pathways. LC-MS/MS characterization identified sweroside and loganic acid as major circulating constituents, while computational analyses prioritized a PPAR-centered target network with favorable binding affinity and structural stability. In the retrospective RIF cohort (n = 100), JWSTW was associated with increased endometrial thickness and improved Doppler-derived perfusion indices. Conclusion: These findings support JWSTW as a mechanism-informed candidate to improve endometrial receptivity in implantation failure via a PPAR-lipid metabolism axis.

INSTRUMENT(S): Liquid Chromatography MS - negative - reverse-phase, Liquid Chromatography MS - positive - reverse-phase

PROVIDER: MTBLS14199 | MetaboLights | 2026-03-31

REPOSITORIES: MetaboLights