Figure 1.

Oocyte Methylation Is a Major Regulator of Trophoblast Gene Expression

(A) Females carrying floxed (f) alleles for Dnmt3a and Dnmt3b as well as a Zp3-driven Cre transgene were crossed to heterozygous males, yielding four different genotypes collectively referred to as mDKO, due to the absence of methylation in the oocyte; conceptuses from females without the Zp3-Cre transgene were used as controls.

(B) Maternal deletion of Dnmt3a/3b results in trophoblast defects at E9.5 (top) characterized by loss of adhesion of TGCs (arrowheads), with no apparent difference in phenotype between different post-zygotic genotypes. In contrast, DKO embryos are more severely affected than DHet embryos (bottom). Images are not on the same scale.

(C) H&E staining of paraffin-embedded sections shows that Dnmt3a mKO trophoblast lacks the labyrinthine layer that is otherwise seen developing in WT trophoblast (marked by an asterisk); the TGC layer is less dense in Dnmt3a KO trophoblast, possibly due to cell adhesion defects. ch, chorion; epc, ectoplacental cone.

(D) Hierarchical clustering of mRNA-seq data from E7.5 EPCs reveals segregation of mDKO and Ctrl genotypes but no further differentiation of individual mDKO genotypes.

(E) mRNA-seq expression values for examples of deregulated genes common to all mDKO genotypes (top), and genes controlled by post-zygotic DNA methylation (bottom). Error bars represent SD.

See also Figure S1.