PNAS:激活休眠卵子
2010年05月30日
来源:PNAS
作者:佚名
责任编辑:lwc
摘要:美国斯坦福大学、日本秋田大学和中国科学院动物研究所的科学家组成的研究小组成功地通过人工手段激活雌鼠卵巢中的原始卵泡,获得了成熟的卵子,然后利用这些卵子繁殖出健康的小老鼠。这一成果刊登在近日出版的美国《国家科学院院刊》上。
美国斯坦福大学、日本秋田大学和中国科学院动物研究所的科学家组成的研究小组成功地通过人工手段激活雌鼠卵巢中的原始卵泡,获得了成熟的卵子,然后利用这些卵子繁殖出健康的小老鼠。这一成果刊登在近日出版的美国《国家科学院院刊》上。
在出生的时候,雌鼠卵巢内就含有一生所需的卵泡,但是几乎都处于休眠状态。在雌鼠性成熟后,有少数卵泡会发育成熟,多数则一直保持在原始卵泡阶段。
在试验中,研究人员从出生3天后的老鼠体内取出卵巢,然后在培养液中培养一至两天,这种培养液中加入了能够让原始卵泡进行细胞分裂的化学物质。接下来将这些被激活的卵泡移植到成熟老鼠的肾脏附近,18天以后就获得了成熟的卵子。这些“特殊”卵子在与精子结合后,发育成为健康的小老鼠。这一技术有可能在未来用来治疗人类的不孕症。
参阅文献:Published online before print May 17, 2010, doi: 10.1073/pnas.1001198107
Activation of dormant ovarian follicles to generate mature eggs
Abstract
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.
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