Fig. 7: LXR-mediated activation of hepatic LC-PUFA-phospholipid biosynthesis, export and fetal transfer in late pregnancy.

A Schematic of the tissues analysed from an independent cohort of wild-type (WT) and Lxrab−/− (LXR double knockout (DKO)) mice at non-pregnant (NP) and various gestational timepoints (7.5, 14.5 and 18.5 dpc). Arrows indicate the hypothesized transfer of LC-PUFA-containing phospholipids between maternal and fetal compartments. B–H RT-qPCR analysis of hepatic LC-PUFA-phospholipid biosynthetic genes in WT and LXR DKO groups. RT-qPCR data was normalised to housekeeping gene expression (Tuba1, Tbp and Hprt) and is shown as mean relative expression ± SD and were compared by two-way ANOVA with Å Ãdák’s multiple comparison (*p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001). WT vs DKO p-values for Fads1: 14.5 dpc = 6.28 × 10−06, 18.5 dpc = 4.83 × 10−05; Fads2: 14.5 dpc = 2.80 × 10−05, 18.5 dpc = 0.0012; Pnpla3: 14.5 dpc = 1.50 × 10−08, 18.5 dpc = 9.54 × 10−08; Mttp: NP = 0.0056, 7.5 dpc = 0.0143, 14.5 dpc = 0.0066; Agpat3: 14.5 dpc = 0.0102. n = 8 (NP WT), n = 7 (NP DKO), n = 8 (7.5 dpc WT), n = 6 (7.5 dpc DKO), n = 7 (14.5 dpc WT), n = 7 (14.5 dpc DKO) n = 7 (18.5 dpc WT), n = 8 (18.5 dpc DKO); mice per condition. I–L Grouped concentrations of ARA-containing PC, DHA-containing PC, ARA-containing PE and DHA-containing PE lipid species selected for targeted LC-MS/MS analysis in liver (I), serum (J), placenta (K) and fetal livers (L) from WT and LXR DKO groups at late-gestational timepoints. Individual lipid concentrations are found in Supplementary Data Table S12. Grouped lipid concentrations are presented as boxplots (median and IQR (25th and 75th percentiles) with whiskers showing 1.5*IQR) with individual values and Bonferroni-adjusted t-tests (p-value threshold = 0.025) were performed for each WT vs DKO comparison (*p-value < 0.05; **p-value < 0.01; ***p-value < 0.001; ****p-value < 0.0001). p-values for (J) - DHA-PC: 14.5 dpc = 0.0009; (L) - DHA-PC: 18.5 dpc = 0.0021; (L) - ARA-PE: 18.5 dpc = 0.0060. n = 7 (14.5 dpc WT), n = 7 (14.5 dpc DKO), n = 7 (18.5 dpc WT; exceptions: n = 6 for placenta), n = 8 (18.5 dpc DKO; exceptions: n = 6 for placenta; n = 7 for fetal liver); mice per condition. ARA arachidonic acid, DHA docosahexaenoic acid, PC phosphatidylcholine, PE phosphatidylethanolamine. Source data are provided as a Source Data file.