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

Safia Malki, Godfried W. vanderHeijden, Kathryn A O'Donnell-Mendell, Sandra L. Martin, Alex Bortvin

Research output: Contribution to journalArticle

84 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)521-533
Number of pages13
JournalDevelopmental Cell
Volume29
Issue number5
DOIs
StatePublished - Jun 9 2014

Fingerprint

Retroelements
Reverse Transcriptase Inhibitors
Ribonucleoproteins
RNA-Directed DNA Polymerase
Oocytes
Defects
Meiotic Prophase I
Proteins
Aneuploidy
Epigenomics
Genetic Recombination
Parturition

ASJC Scopus subject areas

  • Developmental Biology

Cite this

A Role for retrotransposon LINE-1 in fetal oocyte attrition in mice. / Malki, Safia; vanderHeijden, Godfried W.; O'Donnell-Mendell, Kathryn A; Martin, Sandra L.; Bortvin, Alex.

In: Developmental Cell, Vol. 29, No. 5, 09.06.2014, p. 521-533.

Research output: Contribution to journalArticle

Malki, Safia ; vanderHeijden, Godfried W. ; O'Donnell-Mendell, Kathryn A ; Martin, Sandra L. ; Bortvin, Alex. / A Role for retrotransposon LINE-1 in fetal oocyte attrition in mice. In: Developmental Cell. 2014 ; Vol. 29, No. 5. pp. 521-533.
@article{8107fddf16054b70b23105dc86df7447,
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.",
author = "Safia Malki and vanderHeijden, {Godfried W.} and O'Donnell-Mendell, {Kathryn A} and Martin, {Sandra L.} and Alex Bortvin",
year = "2014",
month = "6",
day = "9",
doi = "10.1016/j.devcel.2014.04.027",
language = "English (US)",
volume = "29",
pages = "521--533",
journal = "Developmental Cell",
issn = "1534-5807",
publisher = "Cell Press",
number = "5",

}

TY - JOUR

T1 - A Role for retrotransposon LINE-1 in fetal oocyte attrition in mice

AU - Malki, Safia

AU - vanderHeijden, Godfried W.

AU - O'Donnell-Mendell, Kathryn A

AU - Martin, Sandra L.

AU - Bortvin, Alex

PY - 2014/6/9

Y1 - 2014/6/9

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=84902008373&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84902008373&partnerID=8YFLogxK

U2 - 10.1016/j.devcel.2014.04.027

DO - 10.1016/j.devcel.2014.04.027

M3 - Article

C2 - 24882376

AN - SCOPUS:84902008373

VL - 29

SP - 521

EP - 533

JO - Developmental Cell

JF - Developmental Cell

SN - 1534-5807

IS - 5

ER -