Fig. 1

Sex differences in placental trophoblast and fetal hypothalamic gene expression are mediated by placental Ogt copy number. a, b Scatterplots of mRNAs with sex differences in trophoblast cell-specific expression at E12.5 (4560 genes, FDR adjusted p < 0.05). a Scatterplot comparing sex differences (black circles) with differences between X^wt/X^wt and X^ogt−/X^wt females (red circles). Trophoblast gene expression patterns with sex differences (black circles) are mimicked by Ogt reduction in female trophoblasts (red circles). b Scatterplot comparing trophoblast sex differences (black circles) with differences between X^ogt−/X^wt and X^wt/Y (red circles). Female patterns of gene expression are masculinized by Ogt reduction in female trophoblasts. c Heatmap of mRNA with sex differences in expression in X^wt/X^wt, X^ogt−/X^wt, X^wt/Y trophoblasts. Expression patterns of trophoblast genes (columns) with sex differences are mimicked by Ogt reduction in female trophoblasts (individual placentas = rows). Z-scores plotted across individuals for each gene. d Venn diagram displaying the number of differentially expressed genes in X^wt/Y vs. X^wt/X^wt (n = 4560 genes), X^ogt−/X^wt vs. X^wt/Y (n = 251 genes), and X^ogt−/X^wt vs. X^wt/X^wt (n = 2197 genes) trophoblasts and the number of differentially expressed genes common in these groups. e A total of 1094 of the 2609 trophoblast genes enriched in X^wt/X^wt relative to X^wt/Y were significantly decreased by trophoblast-specific Ogt reduction (X^ogt−/X^wt). f A total of 432 trophoblast genes with increased relative expression in X^wt/Y were enhanced in X^ogt−/X^wt relative to X^wt/X^wt. g Only 7 of the 2609 genes with X^wt/X^wt-biased sex differences in expression were upregulated by trophoblast-specific Ogt reduction (X^ogt−/X^wt). h A total of 4 of the 1951 X^wt/Y-biased genes with basal sex differences were downregulated in X^ogt−/X^wt trophoblasts. N = 3 X^wt/Y, n = 4 X^wt/X^wt, and n = 5 X^ogt−/X^wt placentas, from five individual litters with n = 1/litter/group to control for litter effects