Investigation of Murine Fertility by Kampo Formula Containing Astragalus Root Enhanced Endometrial Wnt/β-catenin Signaling Factors

Astragalus root (Root of Astragalus membranaceaus (Fisch.) Bunge or Astragalus membranaceus var. mongholicus (Bunge) P.K.Hsiao) is a prescription drug constituting Kampo formulae with the aim of cardiotonic, hidroschesis, diuresis, and hypotensive effect in Japan. In this study, we report that hot water extract of Astragalus root (AsR) increased the number of neutrophils and the secretion of mucus from the endocervical gland in ovariectomized mice treated with estradiol. These secretions block bacterial access through the uterine cavity. Moreover, AsR and its main chemical component, AstragalosideⅣ, increased the levels of uterine Wnt4 and Wnt7a involved in endometrial proliferation and the maintenance of the stromasmooth muscle boundaries of the uterus, respectively. To explore the possibility of fertility improvement, we determine the litter size of maternal mice administrated with hot-water extract of Astragalus root or Kampo formula containing Astragalus root. AsR-treated maternal mice exhibited increased litter size by natural mating, whereas Keishikaogito which is a Kampo formula containing Astragalus root showed a trend towards decreased the litter size. These results suggest that Astragalus root mediates endometrial proliferation, leading to the improved fertility; a crude drug-component of Keishikaogito, except Astragalus root, might interfere with embryo implantation. The discovery of Kampo formulae showing increase of litter size is needed for treatment of fertility in medical care.