A role for retrotransposon LINE-1 in fetal oocyte attrition in mice
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Fetal oocyte attrition (FOA) is a conserved but poorly understood process of elimination of more than two-thirds of meiotic prophase I (MPI) oocytes before birth. We now implicate retrotransposons LINE-1 (L1), activated during epigenetic reprogramming of the embryonic germline, in FOA in mice. We show that wild-type fetal oocytes possess differential nuclear levels of L1ORF1p, an L1-encoded protein essential for L1 ribonucleoprotein particle (L1RNP) formation and L1 retrotransposition. We demonstrate that experimental elevation of L1 expression correlates with increased MPI defects, FOA, oocyte aneuploidy, and embryonic lethality. Conversely, reverse transcriptase (RT) inhibitor AZT has a profound effect on the FOA dynamics and meiotic recombination, and it implicates an RT-dependent trigger in oocyte elimination in early MPI. We propose that FOA serves to select oocytes with limited L1 activity that are therefore best suited for the next generation.
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Treating pregnant female mice with the nucleoside analogue azidothymidine (AZT) blocks oocyte attrition and improves oocyte viability in embryos.
“It was shown that treating pregnant female mice with the nucleoside analogue azidothymidine (AZT) blocked oocyte attrition and improved the oocyte viability in embryos (Malki et al., 2014).”
From Cytoplasmic DNA: sources, sensing, and role in aging and disease (2021) · cites this paper as Malki et al., 2014
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- Authors
- Malki, S., van der Heijden, G. W., O’Donnell, K. A., Martin, S. L., & Bortvin, A.
- Affiliations
- Carnegie Institution for Science (US)
- The University of Texas Southwestern Medical Center (US)
- University of Colorado Anschutz (US)
- Corresponding author
- Bortvin, Alex
- Venue
- Developmental Cell
- Publisher
- Elsevier BV
- Published
- 2014-06
- Volume
- 29
- Issue
- 5
- Pages
- 521-533
- ISSN
- 1534-5807 (ISSN-L)
- PMC
- PMC4056315
- OpenAlex
- W1994831927
- Cited by
- 215
- References
- 85
- Citations by year
- 2026: 8 · 2025: 17 · 2024: 12 · 2023: 14 · 2022: 15 · 2021: 21 · 2020: 25 · 2019: 20 · 2018: 20 · 2017: 21 · 2016: 20 · 2015: 18 · 2014: 4
- FWCI
- 20.63
- Type
- journal article
- Language
- en
- Update notices
- erratum (2019-12-02)
- Open access
- bronze
- doi.org
- Licence
- Locations
- Developmental Cell (publishedVersion)
- PubMed (publishedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of General Medical Sciences (GM-40367, R01GM040367)
- Topics
- Health Sciences › Medicine › Public Health, Environmental and Occupational Health › Reproductive Biology and Fertility
- Life Sciences › Agricultural and Biological Sciences › Plant Science › Chromosomal and Genetic Variations
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities
- Keywords
- LINE-1 retrotransposons, meiotic prophase I, oocyte aneuploidy, embryonic lethality, meiotic recombination, oocyte selection
- MeSH terms
- Meiotic Recombination Protein SPO11, Aneuploidy, Animals, DNA Damage, DNA-Binding Proteins, Embryo, Mammalian, Endodeoxyribonucleases, Female, Fetus, Ovarian Follicle, Male, Meiosis, Mice, Inbred C57BL, Oocytes, Ovary, Transcription Factors, Zidovudine, Long Interspersed Nucleotide Elements, Mice
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
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