A Role for Retrotransposon LINE-1 in Fetal Oocyte Attrition in Mice

Dev Cell. 2014 Jun 9;29(5):521-533. doi: 10.1016/j.devcel.2014.04.027. Epub 2014 May 29.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aneuploidy
  • Animals
  • DNA Damage / drug effects
  • DNA-Binding Proteins / physiology*
  • Embryo, Mammalian / cytology
  • Embryo, Mammalian / drug effects
  • Embryo, Mammalian / metabolism
  • Endodeoxyribonucleases / physiology*
  • Female
  • Fetus / cytology*
  • Fetus / drug effects
  • Fetus / metabolism
  • Long Interspersed Nucleotide Elements / genetics*
  • Male
  • Meiosis / drug effects
  • Meiosis / physiology*
  • Mice
  • Mice, Inbred C57BL
  • Oocytes / cytology*
  • Oocytes / drug effects
  • Oocytes / metabolism
  • Ovarian Follicle / cytology
  • Ovarian Follicle / drug effects
  • Ovarian Follicle / metabolism
  • Ovary / cytology*
  • Ovary / drug effects
  • Ovary / metabolism
  • Transcription Factors / physiology*
  • Zidovudine / pharmacology

Substances

  • DNA-Binding Proteins
  • Transcription Factors
  • maelstrom protein, mouse
  • Zidovudine
  • Endodeoxyribonucleases
  • meiotic recombination protein SPO11