先前Cell雜志報(bào)道一篇由麻省綜合醫(yī)院被的研究成果：血液或骨髓中來源的間質(zhì)干細(xì)胞能夠形成小鼠的卵母細(xì)胞,，最新的美國Joslin糖尿病研究的研究證實(shí)：成年雌性小鼠的卵母細(xì)胞不能由血液或骨髓中的生殖細(xì)胞形成,！如果麻省的研究成果成立的話,，雌性哺乳動(dòng)物只能產(chǎn)生確定數(shù)量的卵母細(xì)胞,，并且如果因損傷或疾病損失掉就不能再補(bǔ)充或再生,。移植歸宿或外圍血細(xì)胞能夠在受體小鼠的卵巢中產(chǎn)生新的卵母細(xì)胞,。這可以產(chǎn)生源源不斷的卵母細(xì)胞,。

        Joslin的這項(xiàng)新研究刊登在最新一期的Nature雜志上,。麻省綜合醫(yī)院的研究曾引起了巨大的轟動(dòng),，因?yàn)樗馕吨撬杓?xì)胞可能成為恢復(fù)雌性生殖能力的一種新資源。他們的研究報(bào)道說移植細(xì)胞能夠從骨髓或血液進(jìn)入到遺傳不孕或接受過化療的雌性小鼠的卵巢中并產(chǎn)生了新的卵母細(xì)胞,。但是他們并沒有研究這些卵母細(xì)胞是否能夠被排卵,，或者骨髓細(xì)胞是否在正常情況下能遷移到卵巢中，作為卵巢再生的一個(gè)正常過程,。

        Joslin的研究人員利用一種人工聯(lián)體（parabiotic）小鼠模型進(jìn)行研究,。這種模型的血管融合在一起,，即兩個(gè)小鼠利用一個(gè)共同的循環(huán)系統(tǒng)。這種模型使研究人員能夠追擦正常情況下在血液中流通的細(xì)胞,。

        使用的小鼠在遺傳上是等同的,，除了其中一個(gè)小鼠的身體表達(dá)了綠色熒光蛋白。因此,，一旦這個(gè)小鼠被聯(lián)合在一起,，任何從表達(dá)熒光蛋白小鼠的血液中運(yùn)動(dòng)到它的非熒光同伴的細(xì)胞都能被確定。

        Wagers和他的研究組利用激素刺激這種聯(lián)體動(dòng)物的排卵作用并檢測從兩只小鼠是否排出了綠色的卵母細(xì)胞,。結(jié)果,，他們發(fā)現(xiàn)綠色熒光小鼠的所有卵母細(xì)胞都是綠色的，而它的聯(lián)體搭檔卻沒有一個(gè)綠色的卵母細(xì)胞,。這證明排出的卵母細(xì)胞不是由通過血管達(dá)到卵巢的細(xì)胞產(chǎn)生的,。

        這些新數(shù)據(jù)表明循環(huán)系統(tǒng)的細(xì)胞通常不能形成能排出的卵母細(xì)胞，因此不可能受精,。這項(xiàng)研究還檢測了因化療受損的卵巢是否在血液循環(huán)細(xì)胞存在下有不同的反應(yīng),。結(jié)果他們再次發(fā)現(xiàn)沒有證據(jù)表明血液細(xì)胞能通過循環(huán)作用在卵巢中生根以及促進(jìn)成熟的、能被排出的卵母細(xì)胞的形成,，而且血細(xì)胞也不能促進(jìn)化療后寄主卵母細(xì)胞的復(fù)原,。

Joslin study refutes recent report that bone marrow can replenish female oocytes

Study shows that circulating bone-marrow derived cells do not contribute to egg formation

Ovulated egg cells, or oocytes, in adult female mice are not formed from germ cells in the blood or bone marrow. That's the conclusion of a new study led by investigators at Joslin Diabetes Center and Harvard University. These findings refute a controversial recent study conducted at Massachusetts General Hospital (MGH), which itself contradicted the long-held belief that female mammals are born with a finite number of oocytes that cannot be replenished or regenerated if lost to injury or disease by suggesting that transplanted bone marrow or peripheral blood cells were capable of generating new oocytes in the ovaries of recipient mice.

The Joslin study will appear in an upcoming issue of Nature and on the journal's Web site on June 14, 2006.

"It was a very important study to do," says Amy J. Wagers, Ph.D., Investigator in Developmental and Stem Cell Biology at Joslin Diabetes Center and Assistant Professor of Pathology at Harvard Medical School. "The suggestion that bone marrow cells might represent a previously unappreciated source of cells capable of restoring female fertility had significant implications for patients undergoing chemotherapy, which often leads to sterility, and for individuals donating or receiving bone marrow cells for transplant, as well as for women experiencing premature menopause."

The MGH study reported that transplanted cells from the bone marrow or blood could enter the ovaries of genetically infertile or chemically sterilized female mice and produce new oocytes but didn't study whether those oocytes could be ovulated, or whether bone marrow cells normally migrate to the ovary as part of a normal process of ovary regeneration. The Joslin study's goal was to find out if that was possible.

Joslin study researchers used a parabiotic mouse model in which pairs of mice are joined using a surgical procedure that enables blood vessels to fuse such that the mice develop a common circulatory system. "It's a very useful model," reports Wagers, "because it allows one to track cells that normally circulate in the blood under physiological conditions."

The mice used were almost genetically identical, except that one member of the pair expressed throughout its body green fluorescent protein (GFP), a gene from jellyfish that causes cells expressing it to glow green under certain wavelengths of light. Thus, once the mice were joined, any cells moving through the circulation from the GFP-expressing mouse to its non-fluorescent partner would be identifiable by their green marking, while cells moving from the non-fluorescent partner to the GFP partner would be identifiable by their lack of green fluorescence.

Wagers and the research team used hormones to stimulate ovulation in the parabiotic pairs after they had been joined for six to eight months and examined ovulated oocytes from both mice for the presence of green cells. They found that all of the oocytes in the GFP-expressing partners were green, while none of the oocytes collected from the non-fluorescent partners were green. This demonstrated that the ovulated oocytes had not been produced by cells that arrived in the ovary through the bloodstream.

"We didn't find any oocytes ovulated in the parabiotic mice that would have been derived from circulating cells. Our data argue that circulating cells don't normally contribute to oocytes that are ovulated and therefore available for fertilization," says Wagers.

The study also tested whether ovaries damaged by chemotherapy might respond differently to the presence of blood-circulating cells. The researchers treated non-fluorescent mice with two chemotherapy drugs that cause ovarian damage, cyclophosphamide and busulfan, and paired them with untreated GFP-expressing partners. However, again they found no evidence that blood cells seed the ovary through the circulation and contribute to mature, ovulated oocytes. In addition, they saw equivalent impairment in the ability of chemotherapy-treated animals to ovulate, whether they were joined to untreated partners or not, suggesting that blood-borne cells did not promote the recovery of host oocytes after chemotherapy.

The MGH study had raised hopes that bone marrow or peripheral blood cell transplants could be used to restore fertility in women having difficulty conceiving, or who were prematurely menopausal or whose eggs were damaged by illness or chemotherapy.

Yet, if bone marrow cells in fact generated ovulated oocytes, this might cause concern in settings of bone marrow transplant for other indications, as the transplanted germ cells would contain the donor's genetic contribution, analogous to a donor egg. However, the Joslin study suggests that this is unlikely to occur.

"Our data indicate that transplanted bone marrow cells or peripheral blood cells are unlikely to contribute to fertilizable oocytes in transplant recipients," says Wagers.

Wagers is a principal faculty member of the Harvard Stem Cell Institute, and her research is focused on the migration and functioning of blood-forming stem cells, found predominantly in the bone marrow, and in muscle-regenerative cells found in skeletal muscle. Her laboratory is broadly interested in adult stem cells and tissue regeneration. Wagers and her team are exploring whether transplants of blood-forming stem cells could be useful in the treatment of autoimmunity, by replacing reactive cells with non-reactive cells and potentially reversing the autoimmune process in diseases such as type 1 diabetes. "Some of the work we're doing may suggest ways to make transplants more effective and less toxic, which could one day have applications in treating diabetes," says Wagers.

原始出處：

Born or made? Debate on mouse eggs reignites p795
Doubts deepen over whether mammals can make new eggs. Kendall Powell
doi:10.1038/441795a
Full Text | PDF (295K)