Japanese scientists have made viable mouse eggs in a laboratory dish, an advance that may offer a new route for treating infertility in people.

日本科學家在實驗器皿里培養了可孵化的老鼠卵子,這一進步或為不孕不育癥患者帶來新的治療方法。

The experiment completes a long-sought quest in reproductive biology: to make sperm and eggs in a lab dish. A year ago, the same core group of scientists at Kyoto University created healthy mouse sperm in the lab.

實驗完成了生殖生物學長期以來的追求:在實驗器皿中制造精子和卵子。一年前由京都大學科學家組成的同一個核心團隊,在實驗室中創造了健康的老鼠精子。


A technique that produced these mice may not work in other mammals.

這種技術不用其他哺乳動物,就可以制造這些老鼠。


It will be even tougher to repeat the trick in people. But if it can ever be done, it has the potential to transform reproductive medicine by enabling both infertile men and women to conceive their own genetic offspring.

將這一技術運用到人類身上甚至更加困難。但一旦成功,它將使生殖醫學大為改觀,因為這樣患有不孕不育癥的男女就能夠生產帶有自己基因的后代了。

Any such advance would also raise thorny ethical questions. In theory, at least, it would allow a man or woman of any age—or even someone who is dead but whose tissues are preserved—to become a parent.

這樣的進展也帶來了尖銳的倫理學問題。理論上,至少能使一名任意年齡的男性或女性——甚至某個早已死去但組織保存下來的人——為人父母。




科學家在實驗室器皿中培養大量老鼠卵子的過程
1.胚胎干細胞:研究者向一只雌性老鼠的胚胎干細胞添加能夠控制細胞生長和分化活動的生長因子及其他化學物質。
2.從上胚層樣細胞到原始生殖細胞:這使得胚胎干細胞轉化為上胚層樣細胞,該種細胞為哺乳動物早期胚胎所特有。加入其他蛋白質后,上胚層樣細胞變為為原始生殖細胞。原始生殖細胞沒有特定性別,但它們可能分化成卵子或者精子。
3.體細胞+原始生殖細胞:研究者接下來移除一只胎鼠卵巢的生殖細胞,保留其體細胞。把先前制造的原始生殖細胞放入實驗器皿,與卵巢中取出的體細胞一起培養。體細胞開始形成大部分身體,包括血液、骨骼與器官。
4.雌性老鼠:將細胞結合體移植入一只成年雌性老鼠體內。四星期后科學家從細胞結合體內分離出了未成熟的卵子。
5.從未成熟的卵子到受精卵:一旦這些卵子在實驗器皿中成熟,就以老鼠精子受精,然后生產出身體健康并能繁衍后代的老鼠。
注:可使用兩種老鼠干細胞。一種是胚胎干細胞,能分化為老鼠的各種組織?;蚋脑斐赡昀鲜蟮某墒旒毎?;這一步驟可將成熟細胞還原為胚胎狀態,然后誘使其演化為卵子或精子。
來源:京都大學
華爾街日報

In such experiments, scientists first figure out which proteins naturally turn primordial cells—a stage between stem cells and specialized cells—into either eggs or sperm. Then they add the same proteins to stem cells in a lab dish and see if it yields the same result.

在這個實驗中,科學家首先找到了能將原始細胞(介于干細胞和特化細胞之間的階段)自然轉化為卵子或精子的蛋白質。然后他們將這些蛋白質加入實驗器皿中的干細胞內,觀察是否能產生同樣作用。

Two kinds of very early-stage cells can be used. One is a stem cell taken from an embryo, which is capable of turning into all other mouse tissue. Alternatively, a mature cell from an adult mouse can be reprogrammed; this step causes the mature cell to revert to an embryonic-like state that can then be coaxed into becoming a sperm or egg.

可以使用兩種早期細胞。一種是胚胎干細胞,能分化為老鼠的各種組織?;蚋脑斐赡昀鲜蟮某墒旒毎?;這一步驟可將成熟細胞還原為胚胎狀態,然后誘使其演化為卵子或精子。

Past efforts did yield sperm and eggs, but they didn't lead to healthy mouse babies, the crucial test to determine whether lab-made eggs or sperm are fully functioning and viable.

過去,科學家們通過努力生產出了精子和卵子,但無法孕育出健康幼鼠。這對檢驗人造卵子或精子是否具備功能和能夠生育至關重要。

In the latest research, Dr. Hayashi and his colleagues created new mouse eggs in the lab, then used them to create healthy offspring. The results were achieved using both types of stem cells—the embryonic and the reprogrammed—reinforcing the validity of the technique, at least in mice.

最近研究中,Hayashi博士及同事在實驗室里造出了新的老鼠卵子,然后用它們制造出了健康后代。使用兩種干細胞都得到了同樣的結果——胚胎干細胞和改造細胞——增加了這一技術的有效性,至少對于老鼠有效。

The Kyoto group began by adding proteins, known as growth factors, to stem cells obtained from a female mouse. Because the proteins control cell growth and differentiation, the stem cells became epiblast-like cells, which are a certain type of cell in the early embryo of a mammal. When other proteins were added, the epiblast-like cells became primordial germ cells.

京都集團開始在里面添加蛋白質,稱之為生長因子,由雌性老鼠那里提取干細胞。由于這種蛋白控制細胞的生長和分化的干細胞變為上胚層樣細胞 。在哺乳動物胚胎早期這是一種特定類型的細胞。當其他蛋白質被添加進去時,上胚層樣細胞 變為原始生殖細胞。

Primordial germ cells aren't of a particular sex, but they can become eggs or sperm depending on which somatic cells surround them. Somatic cells are non-germ cells that go on to form much of the body, including blood, bone and organs.

原始生殖細胞沒有特定的性別,但它們根據體細胞周圍環境可以變成卵子或精子。體細胞都是非生殖細胞,繼續生長形成身體的大部分,包括血液,骨骼和器官。

The scientists obtained a fetal mouse ovary and removed its germ cells, but left the somatic cells in place. The previously made primordial germ cells were cultured with the somatic cells, and the mix was transplanted into an adult female mouse.

科學家們從幼兒老鼠獲取卵巢,除去它的生殖細胞,用體細胞填充到那里。原來的與體細胞胞一起培養原始生殖細,則混合移植到成年雌性老鼠身體中。

Four weeks later, scientists removed the transplanted cells and isolated the immature eggs that had grown in the mix. They matured them in a lab dish. The eggs were put in a test tube and fertilized with mouse sperm. The resulting embryos were transferred to female mice, some of which yielded healthy and fertile mice pups.

一個月后,科學家取出移植細胞并從混合的細胞中分理處未成熟的卵子。之后在培養基中孵育成熟。然后,這些卵子在試管中受精。最后將受精的卵子培養成早期胚胎并移植到成年的雌性小鼠子宮中,其中的一些小鼠成功發育出生。


In a control group, where natural mouse eggs were used, nearly 13% of transferred embryos led to healthy, fertile pups. By comparison, the figure was 3.9% for lab-made eggs created from embryonic stem cells, and 1.8% for lab-made eggs created via reprogramming.

在適當條件下,用天然卵細胞發育成的胚胎進行胚胎移植的成活率(13%)比人造卵細胞的成活率(3.9%)高的多。同時,相比之下,用干細胞轉換的卵細胞胚胎移植的成功率(3.9%)比用重編程的體細胞的(1.8%)高得多.

There is no guarantee the technique would work on human cells. The growth-factor proteins that work in mice, for example, are different than the ones needed for human cells.

目前還不能證明這項技術同樣適用于人類,畢竟老鼠和人類發育所需的生長調控因子還是有差異的。

Still, the experiments are likely to offer useful insights into how a primordial cell gets converted into a specialized egg or sperm, a process that is poorly understood today.

盡管如此,這項技術為干細胞的定向誘導分化提供了新的思路。

And while the latest work has a touch of "cellular alchemy," as Dr. Daley puts it, scientists need to see if the technique will work on other mammals. That effort is under way. Dr. Hayashi said his colleague and co-author of the study, Mitinori Saitou, is in the early stages of trying to make sperm and eggs from primate cells.

Dr. Daley 解釋說,最新的研究進展涉及到復雜的干細胞技術,科學家們這在研究這項技術能不能同樣適用于其他哺乳動物。Dr. Hayashi說她的同事Mitinori Saitou最近正在嘗試用高等靈長類動物重復試驗。