Pregnancy and estrogen enhance neural progenitor-cell proliferation in the vomeronasal sensory epithelium

International audienceThe hormonal state during the estrus cycle or pregnancy produces alterations on female olfactory perception that are accompanied by specific maternal behaviors, but it is unclear how sex hormones act on the olfactory system to enable these sensory changes. Herein, we show that the production of neuronal progenitors is stimulated in the vomeronasal organ (VNO) epithelium of female mice during a late phase of pregnancy. Using a wide range of molecular markers that cover the whole VNO cell maturation process in combination with Ca(2+) imaging in early postmitotic neurons, we show that newly generated VNO cells adopt morphological and functional properties of mature sensory neurons. A fraction of these newly generated cells project their axons to the olfactory forebrain, extend dendrites that contact the VNO lumen, and can detect peptides and urinary proteins shown to contain pheromone activity. High-throughput RNA-sequencing reveals concomitant differences in gene expression in the VNO transcriptomes of pregnant females. These include relative increases in expression of 20 vomeronasal receptors, of which 17 belong to the V1R subfamily, and may therefore be considered as candidate receptors for mediating maternal behaviors. We identify the expression of several hormone receptors in the VNO of which estrogen receptor α (Esr1) is directly localized to neural progenitors. Administration of sustained high levels of estrogen, but not progesterone, is sufficient to stimulate vomeronasal progenitor cell proliferation in the VNO epithelium. Peripheral olfactory neurogenesis driven by estrogen may contribute to modulate sensory perception and adaptive VNO-dependent behaviors during pregnancy and early motherhood

Additional file 2: of Pregnancy and estrogen enhance neural progenitor-cell proliferation in the vomeronasal sensory epithelium

Excel workbook containing the mapping statistics of the RNAseq data for each sample, along with the accession numbers for the raw data; the normalized counts for the whole transcriptome; the differential expression analysis between the pregnant and control samples; the gene ontology categories significantly overrepresented in the differentially expressed genes; the normalized counts for the VR genes, accounting for total VSN number; and the differential expression analysis on the VR genes only, after normalization for VSN number, between the pregnant and control samples. The column ‘length’ corresponds to the total exonic bases in all transcripts from the gene. For the differential expression sheets, the columns contain the following data: ‘baseMean’, corresponds to the mean normalized expression value for the gene across all samples; ‘log2FoldChange’, is the fold change between the pregnant and control samples, log2 transformed; ‘lfcSE’, corresponds to the standard error associated with the fold change estimation; ‘stat’, is the Wald statistic; ‘pvalue’ is the P value of the test; and ‘padj’ is the P value after adjusting for multiple testing (Benjamini-Hochberg). Genes that have both their ‘pvalue’ and ‘padj’ set to NA contain outliers; genes with only their ‘padj’ set to NA were filtered prior to the test because their normalized counts were too low. (XLSX 11150 kb