美國斯坦福大學(xué)、日本秋田大學(xué)和中國科學(xué)院動物研究所的科學(xué)家組成的研究小組成功地通過人工手段激活雌鼠卵巢中的原始卵泡,,獲得了成熟的卵子,,然后利用這些卵子繁殖出健康的小老鼠。這一成果刊登在近日出版的美國《國家科學(xué)院院刊》上,。
在出生的時候,,雌鼠卵巢內(nèi)就含有一生所需的卵泡,但是幾乎都處于休眠狀態(tài),。在雌鼠性成熟后,有少數(shù)卵泡會發(fā)育成熟,,多數(shù)則一直保持在原始卵泡階段,。
在試驗中,,研究人員從出生3天后的老鼠體內(nèi)取出卵巢,然后在培養(yǎng)液中培養(yǎng)一至兩天,,這種培養(yǎng)液中加入了能夠讓原始卵泡進行細(xì)胞分裂的化學(xué)物質(zhì),。接下來將這些被激活的卵泡移植到成熟老鼠的腎臟附近,18天以后就獲得了成熟的卵子,。這些“特殊”卵子在與精子結(jié)合后,,發(fā)育成為健康的小老鼠。這一技術(shù)有可能在未來用來治療人類的不孕癥,。(生物谷Bioon.com)
生物谷推薦原文出處:
PNAS doi: 10.1073/pnas.1001198107
Activation of dormant ovarian follicles to generate mature eggs
Jing Lia, Kazuhiro Kawamurab, Yuan Chenga, Shuang Liuc, Cynthia Kleina, Shu Liuc, En-Kui Duanc, and Aaron J. W. Hsueha,1
aDepartment of Obstetrics and Gynecology, Program of Reproductive and Stem Cell Biology, Stanford University School of Medicine, Stanford, CA 94305-5317;
bDepartment of Obstetrics and Gynecology, Akita University School of Medicine, Akita 010-8543, Japan; and
cState 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.