Purpose of Investigation: Ovarian aging remains a difficult
problem in infertility treatment. The traditional oriental herbs have been widely
used for female infertility treatment. This study investigated the effect of
seven oriental herbs mixture (Jogyeongbohyeoldan, JBD) on ovarian aging and
oocyte quality in aged and premature ovarian failure female mice.
Materials and Methods: C57BL/6 female mice aged 12 months (natural
ovarian aging, NOA) were administered once daily with JBD of 15 mg/kg (n 7) and
30 mg/kg (n 7) of body weight for 4 weeks using syringe with oral zoned needle.
The control group (n 7) was treated with normal saline. After final treatment
of JBD, follicle counts were evaluated by hematoxylin and eosin (H&E) staining,
and ovarian mRNA expressions of genes related to PI3K/mTOR (4E-BP1, S6K1, RPS6)
and Hippo (MST1, LATS1) signaling pathway, and angiogenesis (VEGF, visfatin, and
SDF-1) were examined by quantitative real-time PCR. In the second
experiment, NOA and premature ovarian failure mice (POF) were treated with JBD (n
7 each), and were superovulated with PMSG and hCG, followed by mated with male.
Numbers of zygotes ovulated and embryo development rate were examined. In the
third experiment, a total of 18 NOA female mice and 24 POF mice were administered
with JBD and mated with males for 2 weeks, and then the pregnancy outcome was
monitored up to 20 days.
Results: JBD significantly increased numbers of primordial,
primary, secondary, and antral/mature follicles, and ovarian mRNA expression of
4EBP1, S6K1, RPS6, MST1, LATS, VEGF, and SDF-1. Also JBD significantly
increased numbers of zygotes retrieved and embryo development rate to blastocyst
in NOA and POF mice compared to controls (P 0.05). JBD treatment
significantly increased pregnancy outcome including number of live birthed pups
in both NOA and POF mice.
Conclusions: These results suggest that JBD can restore
ovarian aging and improve ovarian function, ovarian response and oocyte quality
in aged mice. It is suggested that this beneficial effect may be related to an
increase in ovarian expression of genes associated with PI3K/mTOR and Hippo
signaling pathways and angiogenesis.