Project description:Pancreatic β-cell mass expands during pregnancy and regresses in the postpartum period in conjunction with dynamic metabolic demands on maternal glucose homeostasis. To understand transcriptional changes driving these adaptations in β-cells and other islet cell types, we performed single-cell RNA sequencing on islets from virgin, late gestation, and early postpartum mice. We identified transcriptional signatures unique to gestation and the postpartum in β-cells, including induction of the AP-1 transcription factor subunits and other genes involved in the immediate-early response (IEGs). Additionally, we found pregnancy and postpartum-induced changes differed within each endocrine cell type, and in endothelial cells and macrophages within islets. Together, our data reveal novel insights into cell-type specific transcriptional changes responsible for adaptations by islet cells to pregnancy and their resolution postpartum.
Project description:The developmental transition to motherhood requires gene expression changes that alter the brain to prepare and drive the female to perform maternal behaviors. Furthermore, it is expected that the many physiological changes accompanying pregnancy and postpartum stages will impact brain gene expression patterns. To understand how extensive these gene expression changes are, we examined the global transcriptional response broadly, by examining four different brain regions: hypothalamus, hippocampus, neocortex, and cerebellum. Further, to understand the time course of these changes we performed RNA-sequencing analyses on mRNA derived from virgin females, two pregnancy time points and three postpartum time points. We find that each brain region and time point shows a unique molecular signature, with only 49 genes differentially expressed in all four regions, across the time points. Additionally, several genes previously implicated in underlying postpartum depression change expression. This study serves as a comprehensive atlas of gene expression changes in the maternal brain in the cerebellum, hippocampus, hypothalamus, and neocortex. At each of the time points analyzed, all four brain regions show extensive changes, suggesting that pregnancy, parturition, and postpartum maternal experience substantially impacts diverse brain regions. Libraries were prepared from three independent biological replicates, mRNA for each biological replicate was derived from a single mouse brain, with each mouse brain being used to collect all four brain regions.
Project description:The developmental transition to motherhood requires gene expression changes that alter the brain to prepare and drive the female to perform maternal behaviors. Furthermore, it is expected that the many physiological changes accompanying pregnancy and postpartum stages will impact brain gene expression patterns. To understand how extensive these gene expression changes are, we examined the global transcriptional response broadly, by examining four different brain regions: hypothalamus, hippocampus, neocortex, and cerebellum. Further, to understand the time course of these changes we performed RNA-sequencing analyses on mRNA derived from virgin females, two pregnancy time points and three postpartum time points. We find that each brain region and time point shows a unique molecular signature, with only 49 genes differentially expressed in all four regions, across the time points. Additionally, several genes previously implicated in underlying postpartum depression change expression. This study serves as a comprehensive atlas of gene expression changes in the maternal brain in the cerebellum, hippocampus, hypothalamus, and neocortex. At each of the time points analyzed, all four brain regions show extensive changes, suggesting that pregnancy, parturition, and postpartum maternal experience substantially impacts diverse brain regions.
Project description:During gestation, sex hormones cause a significant thymic involution which enhances fertility. This thymic involution is rapidly corrected following parturition. As thymic epithelial cells (TECs) are responsible for the regulation of thymopoiesis, we analyzed the sequential phenotypic and transcriptomic changes in TECs during the postpartum period in order to identify mechanisms triggering postpartum thymic regeneration. In particular, we performed flow cytometry analyses and deep RNA-sequencing on purified TEC subsets at several time points before and after parturition. We report that pregnancy-induced involution is not caused by loss of TECs since their number does not change during or after pregnancy. However, during pregnancy, we observed a significant depletion of all thymocyte subsets downstream of the double-negative 1 (DN1) differentiation stage. Variations in thymocyte numbers correlated with conspicuous changes in the transcriptome of cortical TECs (cTECs). The transcriptomic changes affected predominantly cTEC expression of Foxn1, its targets and several genes that are essential for thymopoiesis. By contrast, medullary TECs (mTECs) showed very little transcriptomic changes in the early postpartum regenerative phase, but seemed to respond to the expansion of single-positive (SP) thymocytes in the late phase of regeneration. Together, these results show that postpartum thymic regeneration is orchestrated by variations in expression of a well-defined subset of cTEC genes, that occur very early after parturition.
Project description:DNA methylation profiles were generating using Illumina HM450 microarrays in a prospective sample blood from the prenatal period of pregnant mood disorder patients who would and would not develop depression post partum. We recruited 54 pregnant women with a history of either Major Depression or Bipolar Disorder (I, II or NOS) and prospectively followed them during pregnancy and after delivery in order to identify genetic and clinical characteristics that precede the development of a postpartum depressive episode. Blood samples profiled were collected at varying time points during pregnancy.
Project description:Supporting healthy pregnancy outcomes requires a comprehensive understanding of the cellular hierarchy and underlying molecular mechanisms during peri-implantation development. Here, we presented a single-cell transcriptome-wide view of the bovine peri-implantation embryo development at day 12, 14, 16 and 18, when most of the pregnancy failure occurs. We defined the development and dynamic progression of cellular composition and gene expression of embryonic disc, hypoblast, and trophoblast lineages during bovine peri-implantation development. Notably, the comprehensive transcriptomic mapping of trophoblast development revealed a previous unrecognized primitive trophoblast cell lineage that are responsible for pregnancy maintenance in bovine prior to the time when binucleate cell emerges. We analyzed novel markers for the cell lineage development during bovine early development. We also identified cell-cell communication signaling underling embryonic and extraembryonic cells interact to ensure proper early development in bovine. Collectively, our work provides foundational information to discover essential biological pathways underpinning bovine peri-implantation development and the molecular causes of the early pregnancy failure during this critical period.
Project description:Inherent hemispheric asymmetry is significant for cognition, language and other functions. An understanding of normal brain and asymmetry development in the early period will further the knowledge of how different hemispheres prioritize specific functions, which is still unknown. We analysed the developmental changes in and asymmetry of the proteome in the bilateral frontal lobes of three foetal specimens in the late first trimester of pregnancy (9, 11, 13 gestational weeks). We found that during this period, the difference in expression between gestational weeks increased, and the difference in asymmetric expression decreased. The patterns of protein expression changes in the bilateral frontal lobes were different. Our results show that brain asymmetry can be observed in the early stage. Researchers can use these findings to further investigate the mechanisms of brain asymmetry.
Project description:To clarify the regenerative mechanism of endometrium after parturition in cows, mRNA expression profiles in bovine endometrium were investigated during postpartum period. after PVP-I treatment in cows. The differentially expressed genes in the endometrium between postpartum days 49-52 and days 99-101 were 23 genes, and they were much lower than those before postpartum days 49-52. This result suggests that endometrial regeneration after parturition is completely accomplished until postpartum days 49-52.