At birth, each human ovary contains about 400,000 follicles, which are the basic functional units that support the development of oocytes. Ovarian follicles remain dormant until they are gradually activated during female reproductive life. It was demonstrated recently using gene knockout mice that the PTEN-PI3K-Akt-Foxo3 pathway had a critical role in keeping the follicles at dormancy. However, it remained unclear whether manipulation of this pathway would achieve the activation of dormant follicles in human ovaries. A latest collaborative study of Chinese, Japanese and American scientists showed that short-term treatment of neonatal mouse ovaries with a PTEN inhibitor and a PI3K activating peptide largely activated dormant follicles which generated mature oocytes that gave birth to healthy and fertile progeny after transplantation into ovariectomized hosts. Similar follicle activation was observed using human ovarian cortical fragments and mature eggs were also generated which were not fertilized due to ethical considerations. This work was led by Aaron J.W. Hsueh’s group at Stanford University School of Medicine. Kazuhiro Kawamurab’s group at Akita University School of Medicine, Japan and Enkui Duan’s group at Institute of Zoology, Chinese Academy of Sciences also contributed to this work. The article was published on May 17th, 2010by PNAS and was introduced as a weekly highlight.

Although PTEN is a well-known tumor suppressor, no cancer malignances were finally found in ovaries subjected to the short-term treatment. Therefore, the success of this research provided a potential method to generate abundant mature human eggs which could hopefully help aging or infertile women to have children as long as there are still dormant follicles present in their ovaries. Besides, women who have their ovarian tissues frozen before cancer therapy might also benefit from this study.

This work was supported by Health Grant R21 HD060864 (to A.J.W.H.), Grant-In-Aid for Young Scientists B Grant 21791539 (to K.K.), the Yamaguchi Endocrine Research Association (to K.K.), Lalor Foundation postdoctoral fellowship (to Y.C.), and National Basic Research Program of China Grant 2007CB947401 (to E.K.D.).

Li J, Kawamura K, Cheng Y, Liu S, Klein C, Liu S, Duan EK, Hsueh AJ. Activation of dormant ovarian follicles to generate mature eggs. Proc Natl Acad Sci U S A. 2010 May 17