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精子如何识别卵子

sperm

 

4月17日出版的英国《自然》杂志上刊登了一项发育生物学最新研究成果:研究人员找到了小鼠卵细胞与精子细胞表面蛋白质Izumo1结合的受体Folr4,正是Izumo1与Folr4的结合完成了卵子的受精过程。该项发现可能助力科学家开发出新避孕药物,并诞生治疗不孕不育症的新方法。同时,在精卵融合过程中,那谜一般的融合机制,已开始向人类展露真容。


精子与卵子相遇、互相识别并融合成新一代的生命,是人体60万亿细胞中会发生的最重要事件之一。科学家长期以来都在寻找精卵膜融合事件的重要因子。2005年,科学家发现了新蛋白质lzumo1(此蛋白质得名于日语婚姻之神“出云”,也是日本一家婚礼神社),其作用是让精子和卵子在受精时融合,而这个蛋白质也决定了雄性的生殖能力。这个位于精子上的蛋白质被发现后,激发了研究人员寻找该蛋白质在卵子细胞膜的对应受体。


位于英国茵格斯顿的韦尔科姆基金会桑格研究院科学家嘉文·莱特及其研究团队,日前发现了这个受体——叶酸受体4(Folr4)。研究人员同时建议把此受体更名为“朱诺”,即古罗马神话中主管生育和婚姻的女神。实验中他们发现,缺少“朱诺”的雌鼠不育,缺乏“朱诺”的卵子也无法和正常的精子相融合。这些新成果,加上过去发现有Izumo1缺陷的雄鼠不育的研究,表明“朱诺”和lzumo1的互动对于正常的受精过程至关重要。


研究人员同时也发现,“朱诺”可能也参与了卵子被一枚精子受精后,为了阻止其他精子再进入而发生的细胞膜改变。他们发现卵子受精后,卵子表面会迅速失去“朱诺”受体,在受精完成30分钟到40分钟后,卵子表面几乎找不到“朱诺”受体了,而这一时间与哺乳动物卵子在正常情况下用来形成阻止其他精子进入的细胞膜改变的时间相符。


此发现让人们得以洞见精卵融合过程中的独特机制。而由于本研究中发现的蛋白质结合关系在其它哺乳动物中也有出现,该项成果将可能助力科学家开发出新的避孕药物,并诞生治疗不孕不育症的新方法。

 

It’s the stuff of 3rd-grade sex ed: sperm meets egg to make baby. But, surprisingly, scientists have actually been in the dark about one crucial step: how the two sex cells recognize each other amidst the fluid frenzy in the Fallopian tubes. Now researchers have announced that they’ve found the missing piece of this fertilization puzzle, and that the discovery could lead to individualized fertility treatments and hormone-free birth control.


Back in 2005, researchers found the first half of the the puzzle: a binding protein on the surface of sperm they called Izumol (after a Japanese marriage shrine). In the decade since then, scientists have been searching for Izumol’s counterpart on egg cells. Essentially, they’d found the plug but couldn’t locate the outlet.


Today researchers at Cambridge announced they’ve found that outlet: a receptor protein on the surface of the egg cell. They’ve found it on the eggs of pigs, opossums, mice and even humans.

 

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Protein Match
Researchers found that the only receptor protein that matched up with the sperm protein was one that had already been discovered and named. Its true purpose had just been misunderstood. The receptor had been previously known as Folr4, and thought to be part of the folate-receptor family.


When researchers put unfertilized eggs in a petri dish and blocked their Folr4 receptors, sperm couldn’t latch on. And when researchers genetically modified female mice to lack Folr4, the mice were sterile.


And what’s even more, the discovery also helps explain how eggs limit themselves to just one sperm invader. By studying eggs fertilized in vitro, researchers found that the Folr4 proteins had all been ejected from the surface of the cell by 30 minutes after fertilization and were floating around the membrane, no longer able to bind with the proteins on the sperm.


The Izumol protein on the surface of the sperm pairs up with the Folr4 (Juno) protein on the unfertilized egg. Once fusion occurs, the egg spits out the remaining Juno proteins to prevent multiple sperm from fertilizing the same egg. Image credit: Nature
Pregnancy on Demand
Understanding how the fertilization process starts is big news—it could lead to specialized fertility treatments as well as non-hormonal birth control. Such a crucial role calls for a name change: The researchers have now dubbed the protein Juno (in honor of the Roman goddess of marriage, or, perhaps, more appropriately, for the 2007 academy award-winning film of the same name).
A simple genetic test could determine if a woman’s infertility is due to a lack of Juno proteins, allowing her to skip all the preliminary fertility treatments that won’t work in her case, and cutting right to the manual injection of sperm. Likewise with contraception, knowing the critical role of this particular protein means that blocking it can render sperm powerless.


Now that scientists have found the two halves of this puzzle, which they published in Nature today, their next step is discovering what other proteins are at play when the sperm and egg actually fuse.