一種哄騙女性的正常休眠的生殖細(xì)胞進(jìn)入活躍狀態(tài)的方法可能讓科學(xué)家?guī)椭ダ系呐曰蛘咴诮邮馨┌Y治療之前冷凍了卵巢的女性生育子女,。
Aaron Hsueh及其同事對小鼠使用了一種遺傳療法從而誘導(dǎo)未受精卵周圍的細(xì)胞群(卵泡)脫離休眠狀態(tài),,其方法是用改變PTEN 和PI3K蛋白質(zhì)活性的分子處理新生小鼠卵巢,此前的研究已經(jīng)證明了這能夠影響動物卵泡的生長,。這組科學(xué)家然后把經(jīng)過處理的這些細(xì)胞群移植到小鼠體內(nèi),,在那里這些移植細(xì)胞發(fā)育成了成熟的產(chǎn)生卵子的卵泡。
成熟卵子在試管中受精,,然后移植到了代孕雌性小鼠體內(nèi),,最終產(chǎn)出了總共20只健康、有生育能力的小鼠幼仔。 這組作者報告說,,對人類細(xì)胞重復(fù)這種技術(shù)導(dǎo)致了休眠的人類卵泡像那些小鼠的細(xì)胞一樣成熟,。然而,由于倫理擔(dān)憂,,這些人類卵子沒有受精,。這組作者說,這項研究可能幫助改善能夠產(chǎn)生子女的有限卵子供應(yīng),,在女性的一生中,,大部分卵子都處于休眠狀態(tài)。(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 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.