Cited by 215Reproductive Biology and FertilityChromosomal and Genetic VariationsGenetic and Clinical Aspects of Sex Determination and Chromosomal Abnormalities

A role for retrotransposon LINE-1 in fetal oocyte attrition in mice

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Malki, Safia, van der Heijden, Godfried W., O’Donnell, Kathryn A., Martin, Sandra L., Bortvin, Alex·2014·Developmental Cell

Abstract

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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Crossref · 10.1016/j.devcel.2014.04.027

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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)
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
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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