https://www.youtube.com/watch?v=zUxPnXgVAu4

 file:///C:/Users/user/Downloads/Science-2015-Holubcova.pdf

大多數胚胎染色體異常是由卵母細胞減數分裂過程中的染色體紡錘體分離錯誤造成的。

人類卵母細胞獨立於中心體或其他微管組織中心組裝減數分裂紡錘體。紡錘體組裝是由染色體和小鳥苷三磷酸酶 Ran 介導的，整個過程需要約 16 小時。

長的紡錘體組裝期的特點是紡錘體固有的不穩定性和異常的著絲粒-微管附著，

容易染色體分離錯誤&人類卵子中高非整倍體率 

人類卵母細胞的減數分裂比有絲分裂更容易出現染色體分離錯誤

核膜破裂[(NEBD)，設置為0小時

微管在大約 5 小時內首次被觀察到， 

染色質介導的紡錘體組裝由 三磷酸鳥苷 (GTP) Ran 驅動。

用二磷酸鳥苷鎖定突變體 Ran T24N 阻斷了(GTP) Ran 驅動功能， 可以觀察到Ran T24N 嚴重延遲微管成核的發生並損害紡錘體組裝

人類卵母細胞中的紡錘體組裝獨立於微管組織中心 (MTOC)，但由染色體介導並依賴於 Ran-GTP

染色體介導的微管成核（約 5 小時）和染色體排列的雙極紡錘體建立（約 16 小時）之間的時期顯示出相當大的紡錘體不穩定性。

人類卵母細胞中微管成核的主要位點是染色體，而不是 MTOC。

由於胞質分裂時染色體的不適當分配，後期落後的染色體增加了非整倍性的可能性。

紡錘體不穩定的卵母細胞也更有可能出現染色體排列缺陷。

染色體分離缺陷可能是由於進展到後期，著絲粒-微管附著異常。

約 80% 的著絲粒正確地附著在微管上，與單個紡錘體桿相連（兩性附著）。

20% 的動粒仍然附著在兩個紡錘體極上（merotelic 附著）

紡錘體的不穩定性可能會阻礙準確的動粒-微管附著的建立，從而促進染色體分離錯誤。

• Most aneuploidy results from chromosome segregation errors during the meiotic divisions of an oocyte, the egg’s progenitor cell.
• Human oocytes assembled a meiotic spindle independently of either centrosomes or other microtubule organizing centers. 
• Instead, spindle assembly was mediated by chromosomes and the small guanosine triphosphatase Ran in a process requiring ~16 hours.
• This unusually long spindle assembly period was marked by intrinsic spindle instability and abnormal kinetochore-microtubule attachments, which favor chromosome segregation errors and provide a possible explanation for high rates of aneuploidy in human eggs.
• Meiosis in human oocytes is more prone to chromosome segregation errors than mitosis
• nuclear envelope breakdown [(NEBD),set to 0 hours
• Microtubules were first observed at ~5 hours, when they started to form a small aster within the chromosome aggregate
• Chromatin-mediated spindle assembly is driven by the small guanosine triphosphatase Ran. Guanosine triphosphate (GTP)
• We blocked its function with the guanosine diphosphate–locked mutant Ran T24N, which acts as a dominant-negative variant of Ran
•  Ran T24N severely delayed the onset of microtubule nucleation and impaired spindle assembly 
• spindle assembly in human oocytes is independent of  microtubule organizing centers (MTOCs) but mediated by chromosomes and dependent on Ran-GTP
• The period between chromosome-mediated microtubule nucleation (~5 hours) and establishment of a bipolar spindle with aligned chromosomes (~16 hours) displayed considerable spindle instability.
• Chromosomes, not MTOCs, serve as major sites of microtubule nucleation in human oocytes.
• Chromosomes that lag behind during anaphase increase the possibility of aneuploidy due to inappropriate partitioning of chromosomes upon cytokinesis.
• Oocytes with unstable spindles were also significantly more likely to have chromosome alignment defects. 
• The chromosome segregation defects could be due to progression into anaphase with abnormal kinetochore-microtubule attachments.
• only ~80% of kinetochores were correctly attached to microtubules, being linked to a single spindle pole (amphitelic attachment). 
• In contrast, 20% of kinetochores remained attached to both spindle poles (merotelic attachment)
• Spindle instability could hinder the establishment of accurate kinetochore-microtubule attachments and thereby promote chromosome segregation errors.