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Cell: 人造精子成真！人类的繁衍不需要男人了？

2021-09-25 MedSci原创 MedSci原创

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国家统计局数据显示，在过去十年中，男性不育的比率一直在上升，主要原因是精子缺乏或精子死亡，人工精子的需求日渐迫切。

国家统计局数据显示，在过去十年中，男性不育的比率一直在上升，主要原因是精子缺乏或精子死亡，人工精子的需求日渐迫切。

人工精子并不是人为制造的精子，只是将人体的精原干细胞用科学的技术提取出来，在体外的环境里培育成精子，最终和卵子结合完成受精的过程。

人造精子研究已经持续了十几年的时间，近日，日本京都大学在Cell Stem Cell上发表的研究表明，小鼠多能干细胞可以分化成有功能的精子，且可以成功孕育出健康、可孕的后代。

人造精子已在小鼠身上实现
 
1994年，美国的研究人员发展了在小鼠间移植精原干细胞的方法。1996年，科研人员将健康雄性老鼠的冷冻精原干细胞，植入了不能生育的雄性老鼠体内之后，后者顺利产生了精子。
 
但是此后数年间，人造精子研究进展不大。直到2003年初，日本研究人员宣布成功地把实验鼠的胚胎干细胞变成了精子细胞。
 
2004年，美国哈佛医学院的研究者报道，他们用雄性老鼠的胚胎干细胞培育出精子细胞，并且把这些精子细胞注入了卵子。这也是首次使用人造精子使卵子受精的报道。同年，新加坡科学家培育出鱼的精原干细胞，并从中培育出了活的成熟鱼精子。 
 
2011 年，小鼠孤雌单倍体胚胎干细胞系首次于体外成功建立，该成果由英国科学家 Wutz 实验室、奥地利科学家 Penninger各自独立完成。
 
2012年，中科院上海生科院生化与细胞所李劲松等团队证实单倍体孤雄干细胞具有可替代精子和快速传递基因修饰能力。以往的所谓“人造精子”都是将干细胞在体外分化变成一个精子，这样的精子是不能分裂，不能扩增的。但是这项研究的孤雄胚胎干细胞是可以在体外不断培养，不断传代的，它具有精子的特性。这是一个完全不同的概念，也是一个重大的突破。
 
2016年2月底，一支由中国科学院、南京医科大学等组成的联合科研团队，利用小鼠的胚胎干细胞，在体外培育出了具有生殖功能的精子细胞，并成功用其繁衍出小鼠后代。结果发表在《Cell Stem Cell》上。
而最近，日本京都大学的研究人员在Cell Stem Cell 上发表的研究表明，小鼠多功能干细胞可以分化成有功能的精子，且这些精子可成功生产健康、可育的后代。
 
多功能干细胞分化成精子，通常分为三个模仿自然发育的阶段：首先，干细胞分化为原始生殖细；然后分化为精原细胞，这是确定男性性别的过程；最后分化为精子。这项研究证明在小鼠上可行，为在试管中产生男性精子提供了很好的模型。
 
临床人造精子技术进展如何？
 
据报道，英国纽卡斯尔大学教授卡里姆·纳耶尼亚和他的同事们报道，可以通过男性骨髓细胞培育“人造精子”的技术。研究小组从男性志愿者身上提取一些骨髓组织，并从中分离出干细胞，将这些干细胞培育成精原细胞。
 
对于大多数男性来说，他们体内的精原细胞最后都能自然发展成为成熟的精子。可以通过手术的方法分离病人的精原细胞，在实验室中设法使这些精原细胞产生具有生殖功能的精子，再将这些精子植入到患者体内或直接冷冻保存，以便择期将妻子的卵子取出进行体外受精；
 
还可能通过核移植的克隆技术生产出携带有不育男子的遗传物质（DNA）的胚胎干细胞，这些胚胎干细胞再经过培育，生产出人造精子。解决这一系列问题，将能用于治疗男性不育症。
 
 
女性也能培育“人造精子”？
 
《西游记》中，唐僧师徒四人路过女儿国，唐僧和八戒误喝了子母河的水竟然怀孕了！后来从女儿国的人口中得知，女儿国没有男子，当她们成年之后就去喝子母河的水，几天后就可以生下一个女孩。这显然是作者的异想天开，但是科学发展至今，科学家或许能做到让女生没有男盆友也能拥有自己的孩子了！
 
人造精子同时也是一项能让女性独立生育的技术。科学家从女性身上提取骨髓细胞，分离出干细胞，将这些干细胞培育成“人造精子”，成熟的女性“人造精子”将可以和卵子进行试管授精，生育繁衍后代。这意味着从理论上来说，利用女性的骨髓细胞产生的“人造精子”，但此举亦引发了巨大的争议和质疑。
 
如果将来真能通过女性骨髓细胞培育出成熟的“人造精子”，并用于孕育后代，那么这些“人造精子”只能生出女儿。因为通过女性细胞培育的“人造精子”中将缺少生育男孩所必需的Y染色体。
 
不过，科学家观察到，只有携带XY染色体的胚胎干细胞才能最终培育出人造精子，而带有女性特征的XX染色体的干细胞，虽然能够形成早期的精原干细胞，却始终无法通过减数分裂的考验。
 
人类的繁衍不需要男人了？
 
李劲松教授提到：从技术上层面可以这么理解，但是从生物进化的角度肯定是不可取的。因为精子的产生在减数分裂中会发生姐妹染色体互换，这是物种进化的一个重要保证。“人造精子”所有精子的遗传信息是完全相同的，缺少了姐妹染色体互换的环节，这对物种进化是非常不利的。
 
临床实践证明，无论是对单基因突变还是多基因突变导致的遗传病，人造精子的修复效果都很显著，是其他技术望尘莫及的。将来如果真要应用到人类，或许可以用于治疗父性携带的遗传疾病。比如说某位父亲有遗传疾病，可以用他的精子构建一个细胞系，在细胞系中把遗传病基因修复好，然后当正常精子使用，生出一个健康的小孩。这其实可以作为个性化的医疗手段。
 
但是这需要该技术非常成熟和完善，目前来说是做不到。另外，将该技术应用到人类，也面临着一些伦理方面的争议和障碍。
 
参考文献
1.Mouse embryonic germ (EG) cell lines: transmission through the germline and differences in the methylation imprint of insulin-like growth factor 2 receptor (Igf2r) gene compared with embryonic stem (ES) cell lines. Development. 1994 Nov;120(11):3197-204.
2.Expression of a specific mouse germ cell nuclear antigen (GCNA1) by early embryonic testicular teratoma cells in 129/Sv-Sl/+ mice. Cancer Lett. 1996 Feb 27;100(1-2):31-6.
Generation of pluripotent stem cells from neonatal mouse testis. Cell. 2004 Dec 29;119(7):1001-12.
3.Germline stem cells and follicular renewal in the postnatal mammalian ovary. Nature. 2004 Mar 11;428(6979):145-50.
4.可体外培养扩增的“人造精子”入选2012年“中国科学十大进展”——专访李劲松研究员.生命的化学. 2013-04-15
5. In vitro reconstitution of the whole male germ-cell development from mouse pluripotent stem cells. Cell Stem Cell. 2021 Sep 1;S1934-5909(21)00342-8.
6. Complete Meiosis from Embryonic Stem Cell-Derived Germ Cells In Vitro. Cell Stem Cell. 2016 Mar 3;18(3):330-40.

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    2021-12-29 zjshifan_98647316

    #人造#

    0

  3. 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    2021-12-25 lichifeng

    不育的男人有希望了

    0

  4. 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    2022-02-05 维他命

    #CEL#

    0

  5. 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    2021-10-13 1230375fm68(暂无昵称)

    恐慌了

    0

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    2021-09-28 喝了多少杯

    把卵子也培养出来吧

    0

  7. 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    2021-09-26 olvrrine

    小日本🇯🇵研究的都是啥玩意儿

    1

    展开1条回复
  8. 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    2021-09-26 随梦飞扬

    李劲松教授提到：从技术上层面可以这么理解，但是从生物进化的角度肯定是不可取的。因为精子的产生在减数分裂中会发生姐妹染色体互换，这是物种进化的一个重要保证。“人造精子”所有精子的遗传信息是完全相同的，缺少了姐妹染色体互换的环节，这对物种进化是非常不利的。

    0

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objectType=article, channel=null, level=null, likeNumber=53, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://cdnapi.center.medsci.cn/medsci/head/2017/08/02/7354b3539aae6a0ccb1e0fff04c12084.jpg, createdBy=205b1984786, createdName=随梦飞扬, createdTime=Sun Sep 26 16:37:22 CST 2021, time=2021-09-26, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1054780, encodeId=ea831054e80f5, content=太牛了吧, beContent=null, objectType=article, channel=null, level=null, likeNumber=34, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210225/1f3a8e64c4dc4559af4d21a37afef10a/3632634089c24e5c807a83138e2529ce.jpg, createdBy=c3d35445259, createdName=悠悠sunny, createdTime=Sat Sep 25 20:51:37 CST 2021, time=2021-09-25, status=1, ipAttribution=), GetPortalCommentsPageByObjectIdResponse(id=1054778, encodeId=93d71054e7891, content=首先有这个实力有这个条件研究这方面的就很少了，然后有心思研究这方面的人才又有多少，有这份精力还不如研究人造肝脏人造肾脏解决当下的肝衰、肾衰问题。, beContent=null, objectType=article, channel=null, level=null, likeNumber=79, replyNumber=0, topicName=null, topicId=null, topicList=[], attachment=null, authenticateStatus=null, createdAvatar=https://img.medsci.cn/20210811/201b0ea75d294b86b28303c6958f3a36/9507d8a00c3d454ab9aa4079d1ed61a8.jpg, createdBy=da265452624, createdName=河池名医, createdTime=Sat Sep 25 20:47:26 CST 2021, time=2021-09-25, status=1, ipAttribution=)]
    2021-09-25 悠悠sunny

    太牛了吧

    0

  10. 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    2021-09-25 河池名医

    首先有这个实力有这个条件研究这方面的就很少了，然后有心思研究这方面的人才又有多少，有这份精力还不如研究人造肝脏人造肾脏解决当下的肝衰、肾衰问题。

    0

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