Erbu Zhuyu decoction improves endometrial angiogenesis via uterine natural killer cells and the PI3K/Akt/eNOS pathway a mouse model of embryo implantation dysfunction.

ABSTRACT

BACKGROUND: We investigated the effect of Erbu Zhuyu decoction (EBZY) on angiogenesis via uterine natural killer (uNK) cells and the PI3K/Akt/eNOS pathway in embryo implantation dysfunction (EID) mice. METHODS: Pregnant mice were randomly divided into blank, model, EBZY, progynova, and aspirin groups. Uteri were excised on the 5th day of pregnancy for analysis. RESULTS: Mice in the model group showed pale uteri, a reduced implantation rate, and lower expression levels of phosphatidylinositol-3-kinase (PI3K), protein kinase B (Akt), endothelial nitric oxide synthase (eNOS) and nitric oxide (NO). Compared to the model group, implantation rates in the medium-dose and high-dose groups of EBZY were significantly higher (P < .05), PI3K and Akt mRNA expression levels in the low-dose group were significantly higher (P < .05, P < .01), and the expression of p-PI3K, p-Akt, and p-eNOS proteins in all treatment groups were significantly increased (P < .01, P < .05). The expression of NO was significantly increased in the low-dose and high-dose groups (P < .01, P < .05, respectively). The level of p-Akt protein in the high-dose group was significantly higher than those in the other treatment groups (P < .01, P < .05). There was no significant difference in the density of uNK cells (P > .05). CONCLUSIONS: EBZY facilitated embryo implantation in EID mice by enhancing endometrial angiogenesis via activation of the PI3K/Akt/eNOS pathway, at least in part. There was no evidence to indicate that EBZY could adjust the expression of uNK.