and vertebrate systems, we suggest two possibilities for KHDC1B in mouse. The ﬁrst possibility is that KHDC1B serves as a translational repressor in oocytes and may fulﬁll a role similar to Maskin. KHDC1B exhibits eIF4E binding activity, and like Maskin KHDC1B protein levels are regu- lated in a cell-cycle– dependent manner (Figure 8). Also of note, we have observed an apparent shift in KHDC1 protein interaction with CPEB during oocyte maturation (Figure 7). In GV-stage oocytes, the two proteins are highly colocalized in the cytoplasm. However, in MI stage oocytes CPEB accu- mulates on the spindle, but KHDC1 staining is excluded. The second possibility is that KHDC1 proteins function like GLD1. GLD1 was originally identiﬁed in C. elegans and is a single KH domain protein and member of the QKI/STAR family. It also acts as a translational repressor (Biedermann et al., 2009), but it may have an activating role as well by helping to recruit the GLD2 polymerase to speciﬁc targets during entry into meiosis (Kimble and Crittenden, 2007). In conclusion, we have characterized two related KH do- main proteins that appear to have distinct functions (Figure 9). KHDC1A may play a role in apoptosis. In the adult ovary, the majority of oocytes that initiate growth are never ovulated. Instead, they undergo atresia and are lost (Mark- strom et al., 2002). Perhaps KHDC1A acts to coordinate cell death during this process. KHDC1B appears to play a role in translational control during oocyte maturation. Based on overexpression studies in Xenopus, it appears to act as an inhibitor of CPEB, and like CPEB (Lin et al., 2010) we pro- pose that it has both nuclear and cytoplasmic functions. These conclusions are based largely on overexpression sys- tems due to the challenges associated with performing bio- chemistry on mouse oocytes. However, knockout models will eventually help elucidate the speciﬁc role of KHDC1 family members during oogenesis and might reveal novel roles for these proteins in other tissue compartments. Addi- tionally, analysis of this gene family may eventually lead to a deeper insight into factors inﬂuencing human fertility. The translational regulators DAZ and the KH domain protein FMR (fragile X mental retardation protein) are associated with azoospermia and premature ovarian failure respec- tively (Fox and Reijo Pera, 2001; Wittenberger et al., 2007). By analogy, changes in KHDC1 expression might underlie some cases of idiopathic infertility in humans. ACKNOWLEDGMENTS We acknowledge Astar Winoto for the gift of the pan-KHDC1 antibody and George Stark for the pWPI lentivirus system. 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