Cytoplasmic lattices in the egg cell supply the early embryo as protein storage sites
卵細胞中的細胞質格子，為充期胚胎提供蛋白質儲存位點。
When mammals have offspring, they invest a lot. Unlike fish or frogs, the embryo cannot develop on its own. It has to implant in the uterus, where it is supplied with everything it needs to survive. Until this happens, the egg cell nourishes the early embryo. Among other things, it provides essential proteins.
當哺乳動物懷有後代時，它們進行大量投資。不像魚或青蛙，胚胎不能自行發育。它必須植入子宮，在那裡供應其生存所需的一切。 在此之前，卵細胞會滋養初期胚胎。其他事項中，它也提供必需的蛋白質。
Researchers led by Melina Schuh at the Max Planck Institute for Multidisciplinary Sciences, together with colleagues in Göttingen, have now elucidated how egg cells store proteins. Their experiments also provide important insights into how errors in protein storage can lead to infertility. Structures of the egg cell that have puzzled scientists for over 60 years play a crucial role in this.
目前，由德國馬克斯普朗克多學科科學研究所，Melina Schuh領導的研究人員們，連同於哥廷根大學醫學中心的同事們，已經闡明卵細胞如何儲存蛋白質。他們的實驗也提供了，諸多於蛋白質儲存中之錯誤，如何導致不孕症的重要洞察力。60多年來，一直困擾科學家們的卵細胞結構物，在此扮演一種至關重要角色。
圖1. 小鼠卵細胞，天然充滿PADI6蛋白質(藍色)。這是細胞質格子的一種標記物及主要成分。細胞核中的DNA以紫紅色顯示。
A mouse egg cell, naturally filled with the protein PADI6 (blue) – a marker and main component of the cytoplasmic lattice. The DNA in the cell nucleus is shown in magenta.
For many couples, parenthood is a long time coming. For some, the desire to have children even remains unfulfilled. The causes are varied and can be found in both men and women. In women, fertility decreases with age and infertility becomes more likely. However, genetic mutations can also contribute to this.
對許多夫婦而言，為人父母是一個漫長的過程。對某些人來說，生孩子的願望甚至仍未實現。原因各式各樣，於男性及女性中，均可發現。於女性中，生育力隨著年齡下降。因此，變得更可能不孕。不過，諸多基因突變，也可能導致此情況。
Analyses of the genetic material of infertile women worldwide have shown that one of the most common genetic causes of female infertility is mutations in certain genes. These contain the blueprints for the protein PADI6 and the protein complex Subcortial Maternal Complex, or SCMC for short. However, it was previously unclear what role these proteins in particular play in infertility.
有關全世界不孕症女性遺傳物質的分析顯示，女性不孕症最常見的遺傳原因之一，是於某些基因中的突變。此些包括PADI6蛋白質及皮質下母體複合物(簡稱SCMC)之蛋白質複合物的模板。不過，此些蛋白質在不孕症中，各自的作用角色，先前不詳。
Scientists led by Melina Schuh have now used imaging techniques to visualize that PADI6 and SCMC are the main components of structures that fill the interior of the egg cell. “The research world has been puzzling for decades about the function and composition of this structure, which we refer to as cytoplasmic lattices,” Max Planck Director Schuh explains.
目前，由Melina Schuh領導的科學家們，使用造影技術來視覺化，填滿卵細胞內部結構物的主要成分PADI6及SCMC。馬克斯普朗克多學科科學研究所所長，Schuh解釋：「幾十年來，有關我們稱為細胞質格子之該結構物的功能及組成，一直感到困惑。」
When the scientists removed the PADI6 and SCMC proteins from mouse egg cells, the cytoplasmic lattice was lost – with fatal consequences. “Mouse egg cells that lacked the cytoplasmic lattices also lacked the proteins required by the early embryo. The development of the embryo came to a halt shortly after fertilization,” the cell biologist says. “We therefore suspected that the cytoplasmic lattices could serve as protein storage sites.”
當此些科學家，從小鼠卵細胞中，移除PADI6及SCMC蛋白質時，細胞質格子遭到，具有致命後果的破滅。該細胞生物學家宣稱：「缺乏細胞質格子的小鼠卵細胞，也缺乏初期胚胎所需的此些蛋白質。於受精後不久，胚胎的發育就停止。因此，我們懷疑，細胞質格子可能充當，蛋白質儲存位點。」
Storing proteins in the egg cell is by no means trivial. This is because egg cells are created in the ovaries of a female mammal from birth and remain functional there for months or even years. Egg cells have to keep their proteins in stock for a correspondingly long time without being degraded or becoming active at the wrong time.
於卵細胞中，儲存蛋白質絕非不重要。這是因為，卵細胞從出生起，就在雌性哺乳動物的卵巢中產生，並在幾個月甚至幾年內保持功能。卵細胞必須將其蛋白質儲存相當長的時間，沒被降解或在錯誤的時間變得活躍。
In the next step, the researchers investigated which proteins are contained in the cytoplasmic lattices. In cooperation with groups led by Henning Urlaub and Juliane Liepe from the Max Planck Institute, they used mass spectrometry and bioinformatics to determine the exact protein inventory of the lattices.
在下一步中，此些研究人員調查研究了，細胞質格子中，具有哪些蛋白質。在與馬克斯普朗克研究所，Henning Urlaub及Juliane Liepe領導之團隊的合作中，他們使用了質譜分析法及生物資訊學，來確定此些格子的確切蛋白質存貨。
As the results showed, the cytoplasmic lattices bind to many proteins that are crucial for embryonic development. “Our results are strong indications that our assumption is correct: The cytoplasmic lattices are the protein storage sites of the egg cell and supply the early embryo with vital proteins,” Schuh points out.
結果顯示，細胞質格子與許多對胚胎發育至關重要的蛋白質結合。Schuh指出：「我們的研究結果證實了，我們的假設正確：細胞質格子是卵細胞的蛋白質儲存位點，且供應初期胚胎不可或缺的蛋白質。」
As they further discovered, the PADI6 and SCMC proteins take on the task of collecting and storing proteins for the early development of the embryo.
如同他們進一步的發現，PADI6及SCMC蛋白承擔著，為胚胎初期發育收集及儲存蛋白質的工作。
“This explains why embryos stop developing shortly after fertilization if these proteins are missing or cannot fulfill their function,” says Ida Jentoft, first author of the study. “We were then interested in whether a defective protein storage site can be replaced if, for example, PADI6 and SCMC are missing due to gene mutations.”
該項研究首要撰文人，Ida Jentoft宣稱：「這解釋了，倘若此些蛋白質缺少或無法實現其功能，在受精後不久，為何胚胎停止發育。之後，我們感興趣於，倘若PADI6及SCMC，由於基因突變而缺少，是否能替換有缺陷的蛋白質儲存位點。」
In experiments, the team succeeded in artificially reintroducing the missing lattice proteins into growing mouse egg cells. With this approach, it may also be possible to rebuild the cytoplasmic lattice in defective human egg cells. According to Jentoft, this could be a promising new approach to treating infertility caused by mutations in the PADI6 and SCMC genes.
於諸多實驗中，該研究團隊成功將缺少的格子蛋白質，人工重新引入生長中的小鼠卵細胞中。以此方法，這或許也可能重建，於有缺陷之人類卵細胞中的細胞質格子。根據Jentoft的說法，這可能是治療，由PADI6及SCMC 基因突變，引起之不孕症的一種有指望新方法。
When asked why it has taken so many decades to decipher the function of the enigmatic lattice structures in the egg cell, Schuh and Jentoft have a short answer: the size of the egg cell and the lack of methods. Egg cells are the giants among the various cell types in mammals. What predestines them for storing proteins makes it difficult to look inside them.
當被問到，為什麼花了幾十年的時間才破解卵細胞中，神秘格子結構物的功能時，Schuh及Jentoft給了一個簡短答案：是因為，卵細胞的大小及缺乏方法。於哺乳動物各種細胞類型中，卵細胞是巨大的細胞。就儲存蛋白質而言，注定了它們，使得難以窺視它們。
“The major methodological challenge was to make the egg cells accessible for the imaging methods we used – high-resolution light microscopy and cryo-electron tomography (cryo-ET). The latter makes it possible to examine molecular structures of the egg cell in 3D under almost natural conditions. This has not been possible until now,” the Max Planck Director explains.
馬克斯普朗克研究所所長解釋：「就我們使用之高解析度光學顯微鏡，及低溫電子斷層掃描(cryo-ET)的造影方法而言，主要之方法學上的挑戰是，使此些卵細胞可資取得。後者使得，在幾乎自然條件下，以3D方式檢查卵細胞的分子結構，成為可能。直到目前，這一直不可能。」
The team‘s breakthrough in this procedure was helped by a tried and tested trick from reproductive medicine.
在此過程中，該團隊的突破得力於，來自生殖醫學一種可靠且經考驗的技巧。
For cryo-ET, cells must first be shock-frozen. The researchers took advantage of the fact that clinics routinely freeze human egg cells for artificial insemination to store them. To protect the egg cells during freezing, the clinics use cryoprotectants.
就cryo-ET而言，首先細胞必須被快速冷凍。此些研究人員利用，通常診所冷凍人類卵細胞，供人工授精使用的細節，來儲存它們。在冷凍過程中，為了保護卵細胞，診所使用冷凍保護劑。
“We had the idea of using the same cryoprotectants to achieve the required rapid freezing of the egg cells,” Rubén Fernández-Busnadiego from the University Medical Center Göttingen reports.
來自德國哥廷根大學醫學中心的Rubén Fernández-Busnadiego報告：「我們有過使用相同的冷凍保護劑，來達成所需之快速冷凍卵細胞的構想。」
“With this technique, we can examine the cytoplasmic lattices in the egg cell and begin to decipher their structure in detail,” Schuh adds. The scientists hope that the new techniques will lead to important advances in egg cell research as well as new therapeutic approaches in the future.
Schuh附言：「以此技術，我們能檢視，於卵細胞中的細胞質格子，並開始詳細解讀它們的結構物。」此些科學家期盼，在卵細胞研究上，及未來新治療方法上，此些新技術能引領出諸多重要進展。
網址：https://www.mpg.de/21055528/1106-bich-protein-stock-for-the-beginning-of-a-new-life-17216463-x?c=2249
翻譯：許東榮
文章定位：
