Project description:Both the fetus and the mother who are involved in maternal anti-fetal rejection during pregnancy show distinct alterations in the peripheral blood transcriptome Total RNA isolated from umbilical cord blood and maternal blood was compared between cases without (Normal) and with maternal anti-fetal rejection (FIRS2) using whole genome DASL assay.
Project description:We analyzed the small RNA composition of mouse placenta/decidua to determine whether there are specific differences in small RNAs during fetal development and in response to maternal immune activation.
Project description:Activation of the maternal immune system during pregnancy can fetal development, which can lead to postnatal susceptibility to a wide range of diseases, including cardiovascular, metabolic and psychiatric disorders. During maternal immune activation (MIA), the maternal body must balance its ressources between mounting an immune response and investing resources into continued metabolism and growth : both essential for survival of the fetus and a successful pregnancy. How the placenta responds to MIA over time and how it can protect the fetus is not well understood, and neither are the fetal consequences of MIA. Here, we characterised the response to an induced acute inflammation in maternal lungs over time across maternal and fetal organs, using a combination of omics-methods, imaging and integrative computational analysis. We found that the placenta, unlike other maternal organs, did not react by inducing a typical inflammatory response, but instead initially induced genes associated to strengthen tissue integrity and simultaneously reduced growth to prevent exposure to potential infections. Afterwards, a return to homeostasis was observed, with heightened biosynthesis and expression of endoplasmic reticulum (ER) stress genes. This mechanism likely protects the fetus from inflammation, as we observed no immune response in the fetal liver transcriptome. Instead, we observed metabolic adaptations in the fetus, including a release of docosahexaenoic acid (DHA) Notably, DHA has a crucial function for fetal brain development , and levels of triglyceride and phosphatidylcholine lipids that are necessary for transportation of DHA to the brain were also increased. This metabolic response is likely a combination of the placental MIA response and temporary maternal fasting, caused by MIA-induced fever and lack of nutrient intake. Our study shows, for the first time, the temporal and systemic response to MIA in lungs across maternal and fetal organs.
Project description:It has been widely reported that obesity adversely impacts reproductive performance of females. However, the effects of maternal obesity on fetal germ cells remain poorly understood. In the present study, by employing a high-fat diet (HFD)-based mouse model, we found that maternal obesity disrupts the chromosomal synapsis and homologous recombination during fetal oogenesis. Moreover, transcriptomic profiling revealed the potential molecular network controlling this process. Of note, the global hypermethylation of genomic DNA in fetal oocytes from obese mouse was detected. Importantly, time-restricted feeding (TRF) of obese mice not only ameliorated the meiotic defects, but also partly restored the epigenetic remodeling in fetal oocytes. In sum, we provide the evidence showing the deficit fetal oogenesis in obese mother, implicating a mechanism underlying the intergenerational effects of environmental insults. TRF may represent a potentially effective approach for mitigating fertility issues in obese patients.
Project description:It has been widely reported that obesity adversely impacts reproductive performance of females. However, the effects of maternal obesity on fetal germ cells remain poorly understood. In the present study, by employing a high-fat diet (HFD)-based mouse model, we found that maternal obesity disrupts the chromosomal synapsis and homologous recombination during fetal oogenesis. Moreover, transcriptomic profiling revealed the potential molecular network controlling this process. Of note, the global hypermethylation of genomic DNA in fetal oocytes from obese mouse was detected. Importantly, time-restricted feeding (TRF) of obese mice not only ameliorated the meiotic defects, but also partly restored the epigenetic remodeling in fetal oocytes. In sum, we provide the evidence showing the deficit fetal oogenesis in obese mother, implicating a mechanism underlying the intergenerational effects of environmental insults. TRF may represent a potentially effective approach for mitigating fertility issues in obese patients.
Project description:Both the fetus and the mother who are involved in maternal anti-fetal rejection during pregnancy show distinct alterations in the peripheral blood transcriptome
Project description:During pregnancy, cells from each fetus travel into the maternal circulation and organs, resulting in the development of microchimerism. Identification of the cell types in this microchimeric population would permit better understanding of possible mechanisms by which they affect maternal health. However, comprehensive analysis of fetal cells has been hampered by their rarity. In this study, we sought to overcome this obstacle by combining flow cytometry with multidimensional gene expression microarray analysis of fetal cells isolated from the murine maternal lung during late pregnancy. Fetal cells were collected from the lungs of pregnant female mice. cDNA was amplified and hybridized to gene expression microarrays. The resulting fetal cell core transcriptome was interrogated using multiple methods including Ingenuity Pathway Analysis, the BioGPS gene expression database, principal component analysis, the Eurexpress gene expression atlas and primary literature. Here we report that small numbers of fetal cells can be flow sorted from the maternal lung, facilitating discovery-driven gene expression analysis. We additionally show that gene expression data can provide functional information about the fetal cells. Our results suggest that fetal cells in the murine maternal lung are a mixed population, consisting of trophoblasts, mesenchymal stem cells and cells of the immune system. The detection of trophoblasts and immune cells in the maternal lung may facilitate future mechanistic studies related to the development of immune tolerance and pregnancy-related complications, such as preeclampsia. Furthermore, the presence and persistence of mesenchymal stem cells in maternal organs may have implications for long-term postpartum maternal health. Comprehensive gene expression microarray analysis of fetal cells isolated from the pregnant murine maternal lung. Seven individual replicates were performed.