Project description:Placental development is modified in response to maternal nutrient restriction (NR) resulting in a spectrum of fetal growth rates. Pregnant sheep carrying singleton fetuses and fed either 100% (n=8) or 50% (NR; n=28) of their National Research Council (NRC) recommended intake from Days 35 to 135 of pregnancy were used to elucidate placentome transcriptome alterations at both Day 70 and 135. NR fetuses were further designated into upper (NR NonSGA; n=7) and lower quartiles (NR SGA; n=7) based on Day 135 fetal weight. At Day 70 of pregnancy, there were 22 genes dysregulated between NR SGA and 100% NRC placentomes, 27 genes between NR NonSGA and 100% NRC placentomes, and 22 genes between NR SGA and NR NonSGA placentomes. These genes mediated molecular functions such as MHC class II protein binding, signaling receptor binding, and cytokine activity. Gene Set Enrichment Analysis (GSEA) revealed significant overrepresentation of genes for natural killer cell-mediated cytotoxicity in NR SGA compared to 100% NRC placentomes and alterations in nutrient utilization pathways between NR SGA and NR NonSGA placentomes at Day 70. Results identify novel factors associated with impaired function in SGA placentomes and potential for placentomes from NR NonSGA pregnancies to adapt to nutritional hardship.
Project description:Placental development is modified in response to maternal nutrient restriction (NR), resulting in a spectrum of fetal growth rates. Pregnant sheep carrying singleton fetuses and fed either 100% (n = 8) or 50% (NR; n = 28) of their National Research Council (NRC) recommended intake from days 35-135 of pregnancy were used to elucidate placentome transcriptome alterations at both day 70 and day 135. NR fetuses were further designated into upper (NR NonSGA; n = 7) and lower quartiles (NR SGA; n = 7) based on day 135 fetal weight. At day 70 of pregnancy, there were 22 genes dysregulated between NR SGA and 100% NRC placentomes, 27 genes between NR NonSGA and 100% NRC placentomes, and 22 genes between NR SGA and NR NonSGA placentomes. These genes mediated molecular functions such as MHC class II protein binding, signaling receptor binding, and cytokine activity. Gene set enrichment analysis (GSEA) revealed significant overrepresentation of genes for natural-killer-cell-mediated cytotoxicity in NR SGA compared to 100% NRC placentomes, and alterations in nutrient utilization pathways between NR SGA and NR NonSGA placentomes at day 70. Results identify novel factors associated with impaired function in SGA placentomes and potential for placentomes from NR NonSGA pregnancies to adapt to nutritional hardship.
Project description:The aim of this study was to identify fetal adaptations to gene expression in our mouse model of intrauterine growth restriction (IUGR). Starting at E6.5, pregnant CD-1 mice received either control (ad libitum) or 70% of ad libitum food (maternal nutrient restriction [MNR]). At E18.5, fetal right liver lobes were collected from 2 pups/litter in litters with 11-15 pups. Frozen liver was homogenized for RNA isolations. Isolated RNA was sequenced on a HiSeq2500 with an average read depth of 23M reads and a range of 17-31M reads per sample. Reads were aligned to the mm9 transcriptome with Bowtie2. Normalization and differential expression was done with DESeq2, ALDex2 and EdgeR, and genes were considered in the study if they were consistent in 2 or more tools (FDR <0.1).
Project description:Concentrations of leptin decline during food restriction. This study was designed to test the hypothesis that some of the effects of maternal food restriction on placental development are mediated by the loss of leptin. Mice were randomized to 3 treatment groups on day 1.5 of pregnancy: (1) ad libitum fed (control) (2) 50% food restriction (restricted) (3) 50% food restriction with leptin replacement (1µg/g body weight/day) (leptin). On day 11.5 placentas were collected, and two placentas from each mother were pooled for microarray analysis.
Project description:Concentrations of leptin decline during food restriction. This study was designed to test the hypothesis that some of the effects of maternal food restriction on placental development are mediated by the loss of leptin.
Project description:Maternal nutrient restriction impairs placental growth and development, but available evidence suggests that adaptive mechanisms exist, in a subset of nutrient restricted (NR) ewes, that support normal fetal growth and do not result in intrauterine growth restriction (IUGR). This study utilized Affymetrix GeneChip Bovine and Ovine Genome 1.0 ST Arrays to identify novel placental genes associated with differential fetal growth rates within NR ewes. Singleton pregnancies were generated by embryo transfer and, beginning on Day 35 of pregnancy, ewes received either a 100% National Research Council (NRC) (control-fed group; n = 7) or 50% NRC (NR group; n = 24) diet until necropsy on Day 125. Fetuses from NR ewes were separated into NR non-IUGR (n = 6) and NR IUGR (n = 6) groups based on Day 125 fetal weight for microarray analysis. Of the 103 differentially expressed genes identified, 15 were upregulated and 88 were downregulated in NR non-IUGR compared to IUGR placentomes. Bioinformatics analysis revealed that upregulated gene clusters in NR non-IUGR placentomes associated with cell membranes, receptors, and signaling. Downregulated gene clusters associated with immune response, nutrient transport, and metabolism. Results illustrate that placentomal gene expression in late gestation is indicative of an altered placental immune response, which is associated with enhanced fetal growth, in a subpopulation of NR ewes.
Project description:Fetal growth restriction (FGR) develops when fetal nutrient availability is compromised and increases the risk for perinatal complications and predisposes for offspring obesity, diabetes and cardiovascular disease later in life. Emerging evidence implicates changes in placental function in altered fetal growth and the subsequent development of adult disease. The susceptibility for disease in response to an adverse intrauterine environment differs distinctly between boys and girls, with girls typically having better outcomes. Here, we test the hypothesis that regulation of the placental transcriptome by moderate nutrient reduction is dependent on fetal sex. We used a non-human primate model of FGR in which maternal global food intake is reduced by 30% starting at gestational day (GD) 30. At GD 165 (term = GD 183) placental genome expression profiling was carried out followed by bioinformatics including pathway and network analysis. Surprisingly, there was no coordinated placental molecular response to decreased nutrient availability when analyzing the data without accounting for fetal sex. In contrast, female placentas exhibited a highly coordinated response that included up-regulation of genes in networks, pathways and functional groups related to programmed cell death and down-regulation of genes in networks, pathways and functional groups associated with cell proliferation. These changes were not apparent in the male placentas. Our data support the concept that female placentas initiate complex adaptive responses to an adverse intrauterine environment, which may contribute to increased survival and better pregnancy outcomes in girls. Total RNA obtained from 165dGA control female (n=3), control male (n=3), nutrient restricted female (n=3), and nutrient restricted male (n=3) pregnancies.
Project description:Intra-uterine growth restriction (IUGR) and fetal overgrowth increase the risk of postnatal health. Maternal nutrition is the major intrauterine environmental factor that alters fetal weight. However, the mechanisms underlying maternal nutrition affect fetal development is not entirely clear. We developed a pig model and used isobaric tags for relative and absolute quantification (iTRAQ) to investigate alterations in the placental proteome were obtained from gilts in normal-energy-intake (Con) and high-energy-intake (HE) group, respectively.At 90 d of gestation, the heavy fetuses were found at the tubal ends and light fetuses at the cervical ends of the uterus in Con group and the heavy fetuses had higher glucose concentration than the light fetuses. However, a higher uniformity was noted in HE group. Placental promote between these two positions indicated that a total of 78 and 50 differentially expressed proteins were detected in Con and HE group, respectively. In Con group, these proteins related to lipid metabolism (HADHA, AACS, CAD), nutrient transport (GLUT, SLC27A1) and energy metabolism (NDUFV1, NDUFV2, ATP5C1). However, the differentially expressed proteins in HE group were mainly participation in transcriptional and translational regulation and intracellular vesicular transport.
Project description:Maternal undernutrition during pregnancy followed by ad libitum access to nutrients during postnatal life induces postnatal metabolic disruptions in multiple species. As skeletal muscle is a major metabolic organ, RNAseq was performed on the longissimus dorsi muscles of slaughter-weight adult females that had been exposed to nutrient-restriction in utero.
Project description:We addressed the molecular mechanisms and biological processes underlying the differences in cerebrum, liver, and muscle gene expression of 50 days fetuses in response to early maternal nutrient restriction. To this end, we employed tissue-to-tissue and tissue-specific network approaches using the genome-wide expression profile of 14 samples for two experimental conditions [Control – CON (n = 7) and 40% nutrient restriction – RES (n = 7)]. After RNA quality control, read mapping was performed with STAR aligner to the bovine ARS-UCD1.2 reference genome. Count normalization was performed by using the VST function from DESEq2. Gene networks were constructed using the PCIT algorithm, whereas differentially co-expressed genes were identified based on the R-package DGCA. Significant gene-gene co-expression was taken based on r > | 0.9| and then filtered by differentially expressed genes and transcription factors. Networks were visualized in Cytoscape, and functional analyses were carried out on Cluego and ShinyGo tools. We found that the cerebrum, liver, and muscle tissues were affected by nutrient restriction leading to differences in transcriptional regulation between CON and RES groups. Furthermore, we shed light on the nutrient-sensing pathways across tissues such as mTOR, PI3K/Akt, and insulin. This project was supported by Agriculture and Food Research Initiative Competitive Grant no. 2016-67016-24946 from the USDA National Institute of Food and Agriculture as well as the USDA-NIFA-AFRI (2018-67011-31708).