Maximizing the ovarian reserve in mice by evading LINE-1 genotoxicity
| العنوان: | Maximizing the ovarian reserve in mice by evading LINE-1 genotoxicity |
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| المؤلفون: | Alex Bortvin, Safia Malki, Marla E. Tharp |
| المصدر: | Nature Communications, Vol 11, Iss 1, Pp 1-13 (2020) Nature Communications |
| بيانات النشر: | Nature Publishing Group, 2020. |
| سنة النشر: | 2020 |
| مصطلحات موضوعية: | 0301 basic medicine, Male, DNA damage, Science, Mutant, General Physics and Astronomy, Retrotransposon, Apoptosis, Biology, Oogenesis, General Biochemistry, Genetics and Molecular Biology, Article, 03 medical and health sciences, Mice, 0302 clinical medicine, Fetus, medicine, Transposition, Animals, Ovarian reserve, Ovarian Reserve, lcsh:Science, Mice, Knockout, Multidisciplinary, Mutagenicity Tests, RNA-Binding Proteins, General Chemistry, G2-M DNA damage checkpoint, Oocyte, Cell biology, Mice, Inbred C57BL, Checkpoint Kinase 2, 030104 developmental biology, medicine.anatomical_structure, Fertility, Long Interspersed Nucleotide Elements, Argonaute Proteins, Oocytes, Female, lcsh:Q, 030217 neurology & neurosurgery, DNA Damage |
| الوصف: | Female reproductive success critically depends on the size and quality of a finite ovarian reserve. Paradoxically, mammals eliminate up to 80% of the initial oocyte pool through the enigmatic process of fetal oocyte attrition (FOA). Here, we interrogate the striking correlation of FOA with retrotransposon LINE-1 (L1) expression in mice to understand how L1 activity influences FOA and its biological relevance. We report that L1 activity triggers FOA through DNA damage-driven apoptosis and the complement system of immunity. We demonstrate this by combined inhibition of L1 reverse transcriptase activity and the Chk2-dependent DNA damage checkpoint to prevent FOA. Remarkably, reverse transcriptase inhibitor AZT-treated Chk2 mutant oocytes that evade FOA initially accumulate, but subsequently resolve, L1-instigated genotoxic threats independent of piRNAs and differentiate, resulting in an increased functional ovarian reserve. We conclude that FOA serves as quality control for oocyte genome integrity, and is not obligatory for oogenesis nor fertility. Mammals lose up to 80% of their finite oocyte supply during fetal development. Here the authors interrogate mechanisms of fetal oocyte attrition in mice, driven by the simultaneous upregulation of LINE-1 retrotransposon activity and inhibit these mechanisms to increase the functional ovarian reserve. |
| اللغة: | English |
| تدمد: | 2041-1723 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::9f82c936fd0fb5bc9f5d31d8d021bff1Test http://link.springer.com/article/10.1038/s41467-019-14055-8Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....9f82c936fd0fb5bc9f5d31d8d021bff1 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 20411723 |
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