Baicalin can attenuate the inhibitory effects of mifepristone on Wnt pathway during peri-implantation period in mice

• Baicalin decreased E2, Dkk1 and increased P4,Wnt4, LRP6, β-catenin.
• Mifepristone decreased Wnt4, LRP6, β-catenin and increased Dkk1.
• Baicalin attenuate the inhibitory effects of mifepristone on Wnt pathway.

Wnts are considered as important factors in uterus developmental process and embryo implantation. Baicalin has been demonstrated to possess tocolytic properties. In order to investigate the effect of baicalin on the Wnt signaling pathway during the peri-implantation, pregnant Kuming mice were randomly divided into four groups: control group, baicalin group administered with 40 mg/kg BW of baicalin through an intragastric gavage on day 2 to 7 of the pregnancy (Pd2–Pd7), mifepristone group treated with 4 mg/kg BW of mifepristone, an abortifacient agent, via subcutaneous administration on Pd4, and baicalin + mifepristone group treated with their combination. The concentrations of the implantation-related steroid hormones (progesterone and estradiol) in the blood serum were measured with RIA. The gene and protein expression levels of the important molecules of the Wnt pathway (Wnt4, LRP6, Dkk1 and β-catenin) in the endometrium were detected with RT-PCR and western blot, respectively. The results showed that baicalin decreased (P < 0.05) the estradiol levels on Pd4–Pd8 and increased (P < 0.05) the progesterone levels on Pd3–Pd8. Mifepristone increased (P < 0.05) the estradiol levels on Pd5–Pd8 and decreased (P < 0.05) the progesterone levels on Pd6–Pd8. Compared with the control group, baicalin increased the gene and protein expression levels of Wnt4, LRP6 and β-catenin (P < 0.05) and decreased the gene and protein expression levels of Dkk1 (P < 0.05) during the middle-to-late stage of the experiment in mice uterine tissue. Baicalin alleviated the mifepristone-induced increase or decrease in the serum levels of progesterone and estradiol, and the gene or protein expression levels of Wnt4, LRP6 and β-catenin. The tocolytic properties tocolysis of baicalin may be realized through regulating the levels of estrogen/progesterone and the important components of canonical Wnt signaling pathway during the embryo implantation process intervened with the subcutaneous administration of mifepristone in the mice.