Female germ cell aneuploidy and embryo death in mice lacking the meiosis-specific protein SCP3.
Aneuploidy (trisomy or monosomy) is the leading genetic cause of pregnancy loss in humans and results from errors in meiotic chromosome segregation. Here, we show that the absence of synaptonemal complex protein 3 (SCP3) promotes aneuploidy in murine oocytes by inducing defective meiotic chromosome segregation. The abnormal oocyte karyotype is inherited by embryos, which die in utero at an early stage of development. In addition, embryo death in SCP3-deficient females increases with advancing maternal age. We found that SCP3 is required for chiasmata formation and for the structural integrity of meiotic chromosomes, suggesting that altered chromosomal structure triggers nondisjunction. SCP3 is thus linked to inherited aneuploidy in female germ cells and provides a model system for studying age-dependent degeneration in oocytes.
Yuan
Li
L
Center for Genomics and Bioinformatics and Department of Cell and Molecular Biology, Karolinska Institutet, SE-171 77 Stockholm, Sweden.
Liu
Jian-Guo
JG
Hoja
Mary-Rose
MR
Wilbertz
Johannes
J
Nordqvist
Katarina
K
Höög
Christer
C
D000782:Aneuploidy; D000818:Animals; D018797:Cell Cycle Proteins; D020090:Chromosome Segregation; D002875:Chromosomes / Q000502:physiology* / Q000648:ultrastructure; D003434:Crossing Over, Genetic; D004268:DNA-Binding Proteins; D020964:Embryo Loss; D005260:Female; D007621:Karyotyping; D008098:Litter Size; D008297:Male; D008423:Maternal Age; D008540:Meiosis; D051379:Mice; D008810:Mice, Inbred C57BL; D009154:Mutation; D009630:Nondisjunction, Genetic; D009687:Nuclear Proteins / Q000235:genetics / Q000502:physiology*; D009865:Oocytes / Q000502:physiology*; D011247:Pregnancy; D011995:Recombination, Genetic; D013573:Synaptonemal Complex / Q000502:physiology / Q000648:ultrastructure
D018797:Cell Cycle Proteins; D004268:DNA-Binding Proteins; D009687:Nuclear Proteins; C490062:Sycp3 protein, mouse