Effect of new zaogong erteng decoction on embryo implantation in mice following treatment of endometritis

Abstract: Background: New zaogong erteng decoction (NZGETD) is a compound Chinese medicine modified from the Zaogong Erteng Decoction. Previous clinical observations suggested its potential efficacy against endometritis, an inflammatory condition that adversely impacts endometrial receptivity and embryo implantation. Objectives: In this study, the role and mechanism of NZGETD in improving embryo implantation were investigated in a mouse model of lipopolysaccharide-induced endometritis. Methods: Female mice were treated with 2.5 mg/mL lipopolysaccharide in the endometrium for 24 h to induce endometritis and were subsequently gavaged with NZGETD for 8 days. Pathological changes, inflammatory cytokine levels, uterine index, endometrial decidualization, microangiogenesis and hormone levels were assessed. Network pharmacology analysis was employed to identify potential active components and targets. The expression of key proteins related to endometrial receptivity and implantation was confirmed by western blotting. Results: NZGETD attenuated lipopolysaccharide-induced pathological changes and downregulated uterine levels of IL-1β, IL-6 and TNF-α, indicating its anti-inflammatory effect in this endometritis model. NZGETD significantly increased the uterine index, promoted endometrial decidualization and microangiogenesis (upregulated CD31 on gestational day 4.5). Additionally, NZGETD significantly elevated uterine levels of estrogen and progesterone and increased the number of implantation sites on gestational day 8.5. Network pharmacology analysis screened beta-sitosterol, quercetin, kaempferol and stigmasterol as the common active components of NZGETD. Western blotting confirmed that NZGETD up-regulated ESR, PGR, Hoxa10, integrin β3, LIF, HIF1α and VEGF during embryo implantation. Conclusion: In a mouse model of lipopolysaccharide-induced endometritis, NZGETD promoted decidualization and microangiogenesis of the endometrium, enhanced endometrial receptivity and facilitated embryo implantation.