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
N1 - Funding Information:
We thank M. Halpern for manuscript critique; N. Ingolia, A. Pinder, and F. Tan for RNA-seq assistance; D. Camerini-Otero for Spo11 mice; and P.J. Wang, B.R. Cullen, and R. Kanaar for antibodies. This work was supported by the endowment of Carnegie Institution for Science, by a CPRIT R1101 award (to K.A.O.) and by NIH grant GM40367 (to S.L.M.). S.M. was a recipient of the EMBO long-term (ALTF 543-2006) and McClintock fellowships. G.W.v.d.H. was a recipient of a Hollaender fellowship.
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
SN - 1534-5807
VL - 29
SP - 521
EP - 533
JO - Developmental cell
JF - Developmental cell
IS - 5
ER -