Figure 9. Proposed effects of LSD1 depletion on meiotic progression in female mice.

LSD1 depletion in growing oocytes leads to elevation of global H3K4me2. One consequence is increased expression of CDC25B, which dephosphorylates and activates CDK1, resulting in precocious meiotic resumption. CDC25B upregulation also contributes to subsequent spindle and chromosomal abnormalities. Other consequences of H3K4me2 elevation, including derepression of retrotransposons, DNA DSBs, altered gene expression and chromatin defects also play important roles in inducing chromosomal abnormalities. Most Lsd1-null oocytes are arrested at meiosis I and undergo apoptosis, and the small number of oocytes that develop to MII oocytes have severe chromosomal and spindle defects and are mostly aneuploidy and unfertilizable.