Effects of Hochuekkito, a traditional Japanese medicine (Kampo), on reproduction of aging female mice

PURPOSE: To determine the potentials of Hochuekkito (HET) treatment for aging infertility. METHODS: Mice at 36 weeks of age were fed without (control, n = 40) or with low (100 mg/kg/day, n = 24) and high (1000 mg/kg/day, n = 38) doses of HET for 12 weeks. Aging animals at 48 weeks of age were used for in vitro fertilization‐embryo transfer (IVF‐ET), and their ovaries were subjected to histological and quantitative inflammation analyses. RESULTS: HET administration decreased transcript levels of ovarian inflammatory markers, interleukin 6 (IL‐6), IL‐1β, tumor necrosis factor (TNF)‐α, and interferon‐gamma (IFN‐γ) but suppressed ovulation rates and the number of ovulated oocytes in aging mice. Furthermore, HET treatment decreased the rates of oocytes maturation and fertilization and the cumulus‐cell expression of TNF‐α‐induced protein 6 and epidermal growth factor receptor. After IVF‐ET, no improvement of declined live offspring rate by aging was achieved by HET administration, although there were no adverse effects on embryo development and implantation as well as gross morphology and bodyweight of pups. CONCLUSION: Present study indicated HET treatment interfered with ovulation and fertilization in aging mice without affecting ovarian follicle development. No improvement on the age‐associated decline of live offspring rate and follicle development was achieved after HET treatment.