Long-term impact of placental allopregnanolone insufficiency on the mouse transcriptome of cerebral cortex, hippocampus, hypothalamus and cerebellum

Goal: To test the long-term influence of placental allopregnanolone (ALLO) loss on mouse brain transcriptome, in a sex- and region-specficic manner. Methods: We deleted the gene encoding the synthetic enzyme for ALLO (Akr1c14) specifically in trophoblasts by crossing Akr1c14-floxed mice with Cyp19a-Cre mice (plKO mice). Region-specific mRNA profiles of 30-day old WT and plKO mice were generated by 3'mRNA sequencing, in triplicate, using Illumina HiSeq 2500. Results: Our RNA sequencing analysis reveals that placental ALLO withdrawal is associated with region- and sex-specific gene expression changes. The differentially expressed genes are notably associated with myelination and autism spectrum disorders. Conclusions: We show that placental ALLO insufficiency is associated with long-term changes in gene expression in the mouse brain in a sex- and region-specific manner. mRNA profiles of 30-day old WT and plKO mice were generated by 3'mRNA sequencing, in triplicate, using Illumina HiSeq 2500.