دورية أكاديمية
Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age.
| العنوان: | Ovulation suppression protects against chromosomal abnormalities in mouse eggs at advanced maternal age. |
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| المؤلفون: | Chatzidaki EE; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Dr. Bohr-Gasse 3, 1030 Vienna, Austria., Powell S; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Dr. Bohr-Gasse 3, 1030 Vienna, Austria., Dequeker BJH; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Dr. Bohr-Gasse 3, 1030 Vienna, Austria., Gassler J; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Dr. Bohr-Gasse 3, 1030 Vienna, Austria., Silva MCC; Research Institute of Molecular Pathology, Campus Vienna BioCenter 1, 1030 Vienna, Austria., Tachibana K; Institute of Molecular Biotechnology of the Austrian Academy of Sciences, Vienna BioCenter, Dr. Bohr-Gasse 3, 1030 Vienna, Austria; Department of Totipotency, Max Planck Institute of Biochemistry, Am Klopferspitz 18, 82152 Martinsried, Munich, Germany. Electronic address: tachibana@biochem.mpg.de. |
| المصدر: | Current biology : CB [Curr Biol] 2021 Sep 27; Vol. 31 (18), pp. 4038-4051.e7. Date of Electronic Publication: 2021 Jul 26. |
| نوع المنشور: | Journal Article; Research Support, Non-U.S. Gov't |
| اللغة: | English |
| بيانات الدورية: | Publisher: Cell Press Country of Publication: England NLM ID: 9107782 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1879-0445 (Electronic) Linking ISSN: 09609822 NLM ISO Abbreviation: Curr Biol Subsets: MEDLINE |
| أسماء مطبوعة: | Publication: Cambridge, MA : Cell Press Original Publication: London, UK : Current Biology Ltd., c1991- |
| مواضيع طبية MeSH: | Meiosis* , Ovulation Inhibition*, Animals ; Cell Cycle Proteins/genetics ; Chromosome Aberrations ; Chromosome Segregation ; Female ; Mammals ; Maternal Age ; Mice ; Oocytes/physiology |
| مستخلص: | The frequency of egg aneuploidy and trisomic pregnancies increases with maternal age. To what extent individual approaches can delay the "maternal age effect" is unclear because multiple causes contribute to chromosomal abnormalities in mammalian eggs. We propose that ovulation frequency determines the physiological aging of oocytes, a key aspect of which is the ability to accurately segregate chromosomes and produce euploid eggs. To test this hypothesis, ovulations were reduced using successive pregnancies, hormonal contraception, and a pre-pubertal knockout mouse model, and the effects on chromosome segregation and egg ploidy were examined. We show that each intervention reduces chromosomal abnormalities in eggs of aged mice, suggesting that ovulation reduction delays oocyte aging. The protective effect can be partly explained by retention of chromosomal Rec8-cohesin that maintains sister chromatid cohesion in meiosis. In addition, single-nucleus Hi-C (snHi-C) revealed deterioration in the 3D chromatin structure including an increase in extruded loop sizes in long-lived oocytes. Artificial cleavage of Rec8 is sufficient to increase extruded loop sizes, suggesting that cohesin complexes maintaining cohesion restrict loop extrusion. These findings suggest that ovulation suppression protects against Rec8 loss, thereby maintaining both sister chromatid cohesion and 3D chromatin structure and promoting production of euploid eggs. We conclude that the maternal age effect can be delayed in mice. An implication of this work is that long-term ovulation-suppressing conditions can potentially reduce the risk of aneuploid pregnancies at advanced maternal age. Competing Interests: Declaration of interests The authors declare no competing interests. (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.) |
| التعليقات: | Comment in: Nat Rev Mol Cell Biol. 2021 Sep;22(9):586. (PMID: 34345034) |
| معلومات مُعتمدة: | P 30613 Austria FWF_ Austrian Science Fund FWF |
| فهرسة مساهمة: | Keywords: 3D chromatin structure; Hi-C; aging; aneuploidy; chromosome segregation; cohesin; contraception; maternal age effect; oocyte; ovulation |
| المشرفين على المادة: | 0 (Cell Cycle Proteins) |
| تواريخ الأحداث: | Date Created: 20210727 Date Completed: 20220406 Latest Revision: 20220406 |
| رمز التحديث: | 20240829 |
| DOI: | 10.1016/j.cub.2021.06.076 |
| PMID: | 34314679 |
| قاعدة البيانات: | MEDLINE |
| تدمد: | 1879-0445 |
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| DOI: | 10.1016/j.cub.2021.06.076 |