Aaron Hsueh及其同事对小鼠使用了一种遗传疗法从而诱导未受精卵周围的细胞群（卵泡）脱离休眠状态，其方法是用改变PTEN 和PI3K蛋白质活性的分子处理新生小鼠卵巢，此前的研究已经证明了这能够影响动物卵泡的生长。这组科学家然后把经过处理的这些细胞群移植到小鼠体内，在那里这些移植细胞发育成了成熟的产生卵子的卵泡。

成熟卵子在试管中受精，然后移植到了代孕雌性小鼠体内，最终产出了总共20只健康、有生育能力的小鼠幼仔。 这组作者报告说，对人类细胞重复这种技术导致了休眠的人类卵泡像那些小鼠的细胞一样成熟。然而，由于伦理担忧，这些人类卵子没有受精。这组作者说，这项研究可能帮助改善能够产生子女的有限卵子供应，在女性的一生中，大部分卵子都处于休眠状态。

原文出处：

PNAS doi: 10.1073/pnas.1001198107

Activation of dormant ovarian follicles to generate mature eggs
Jing Li a, Kazuhiro Kawamur a b, Yuan Cheng a, Shuang Liu c, Cynthia Klein a, Shu Liu c, En-Kui Duan c, and Aaron J. W. Hsueh a,1

a Department of Obstetrics and Gynecology, Program of Reproductive and Stem Cell Biology, Stanford University School of Medicine, Stanford, CA 94305-5317;
b Department of Obstetrics and Gynecology, Akita University School of Medicine, Akita 010-8543, Japan; and
c State Key Laboratory of Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, Beijing 100101, People's Republic of China

Although multiple follicles are present in mammalian ovaries, most of them remain dormant for years or decades. During reproductive life, some follicles are activated for development. Genetically modified mouse models with oocyte-specific deletion of genes in the PTEN-PI3K-Akt-Foxo3 pathway exhibited premature activation of all dormant follicles. Using an inhibitor of the Phosphatase with TENsin homology deleted in chromosome 10 (PTEN) phosphatase and a PI3K activating peptide, we found that short-term treatment of neonatal mouse ovaries increased nuclear exclusion of Foxo3 in primordial oocytes. After transplantation under kidney capsules of ovariectomized hosts, treated follicles developed to the preovulatory stage with mature eggs displaying normal epigenetic changes of imprinted genes. After in vitro fertilization and embryo transfer, healthy progeny with proven fertility were delivered. Human ovarian cortical fragments from cancer patients were also treated with the PTEN inhibitor. After xeno-transplantation to immune-deficient mice for 6 months, primordial follicles developed to the preovulatory stage with oocytes capable of undergoing nuclear maturation. Major differences between male and female mammals are unlimited number of sperm and paucity of mature oocytes. Thus, short-term in vitro activation of dormant ovarian follicles after stimulation of the PI3K-Akt pathway allows the generation of a large supply of mature female germ cells for future treatment of infertile women with a diminishing ovarian reserve and for cancer patients with cryo-preserved ovaries. Generation of a large number of human oocytes also facilitates future derivation of embryonic stem cells for regenerative medicine.