title: A role for retrotransposon LINE-1 in fetal oocyte attrition in mice.
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.
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
authors.forename: Safia
authors.initials: S
authors.lastname: Malki
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA.
authors.forename: Godfried W
authors.initials: GW
authors.lastname: van der Heijden
authors.affiliation: Department of Molecular Biology, University of Texas Southwestern Medical Center, Dallas, TX 75390, USA.
authors.forename: Kathryn A
authors.initials: KA
authors.lastname: O'Donnell
authors.affiliation: Department of Cell and Developmental Biology, University of Colorado School of Medicine, Aurora, CO 80045, USA.
authors.forename: Sandra L
authors.initials: SL
authors.lastname: Martin
authors.affiliation: Department of Embryology, Carnegie Institution for Science, Baltimore, MD 21218, USA. Electronic address: bortvin@ciwemb.edu.
authors.forename: Alex
authors.initials: A
authors.lastname: Bortvin
mesh_terms: D000782:Aneuploidy; D000818:Animals; D004249:DNA Damage / Q000187:drug effects; D004268:DNA-Binding Proteins / Q000502:physiology*; D004622:Embryo, Mammalian / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D004706:Endodeoxyribonucleases / Q000502:physiology*; D005260:Female; D005333:Fetus / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D020084:Long Interspersed Nucleotide Elements / Q000235:genetics*; D008297:Male; D008540:Meiosis / Q000187:drug effects / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D009865:Oocytes / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D006080:Ovarian Follicle / Q000166:cytology / Q000187:drug effects / Q000378:metabolism; D010053:Ovary / Q000166:cytology* / Q000187:drug effects / Q000378:metabolism; D014157:Transcription Factors / Q000502:physiology*; D015215:Zidovudine / Q000494:pharmacology; D000099257:Meiotic Recombination Protein SPO11
chemical_list: D004268:DNA-Binding Proteins; D004706:Endodeoxyribonucleases; D014157:Transcription Factors; D015215:Zidovudine; D000099257:Meiotic Recombination Protein SPO11; C531147:maelstrom protein, mouse