Project description:Microarray analysis of human fetal microglia from the mid-trimester period was performed. DEGs were identified between early and late stages of the mid-trimester gestation. Genes expressed in the human fetal microglia were also compared with mouse microglia core signature.
Project description:The goal of this study was to transciprtionally profile the three layers of the human placenta (decidua, fetal membrane and placental villi) from the mid-gestation healthy human placenta.
Project description:Human placenta bulk small RNA-seq from healthy pregnancies without infertility, from n=113 first trimester (58 female, 55 male) and n=47 third trimester (19 female, 28 male) tissue samples. Tissue was collected at Cedars-Sinai Medical Center in Los Angeles, California, USA. First trimester placenta was collected at 70-102 days of gestation from leftover chorionic villus sampling for prenatal genetic diagnosis. Third trimester placenta was collected after delivery at 254-290 days gestation from the fetal side near the umbilical cord insertion site beneath the amnion. Mothers with pre-existing diabetes or hypertension were excluded. All pregnancies were conceived without fertility treatments, were normal karyotype, and resulted in live singleton births. The average parental age was advanced (over 35 years old) but PCA analysis did not show clustering by either maternal or paternal age. Gonzalez et al 2021 [PMID: 34030457] analyzes similarities and differences between first and third trimester miRNA expression overall. Flowers et al 2021 focuses on the effect of fetal sex on miRNA expression across gestation.
Project description:Background: Maternal iron deficiency (ID) is associated with poor pregnancy and fetal outcomes. The effect is thought to be mediated by the placenta but there is no comprehensive assessment of placental response to maternal ID. Additionally, whether the influence of maternal ID on the placenta differs by fetal sex is unknown. Objectives: Our primary aim was to identify gene and protein signatures of ID mouse placentas at mid-gestation. A secondary objective was to profile the expression of iron genes in mouse placentas across gestation. Methods: We used a real-time PCR based array to determine the mRNA expression of all known iron genes in mouse placentas at embryonic day (E) 12.5, E14.5, E16.5, and E19.5 (n=3 placentas/time point). To determine the effect of maternal ID, we performed RNA sequencing and proteomics in male and female placentas from ID and iron adequate mice at E12.5 (n=8 dams/diet). Results: In female placentas, six genes including transferrin receptor (Tfrc) and solute carrier family 11 member 2 were significantly changed by maternal ID. An additional 154 genes were altered in male ID placentas. Proteomic analysis quantified 7662 proteins in the placenta. Proteins translated from iron responsive element (IRE) containing mRNAs were altered in abundance; ferritin and ferroportin 1 decreased while TFRC increased in ID placenta. Less than 4% of the significantly altered genes in ID placentas occurred both at the transcriptional and translational levels. Conclusions: Our data demonstrate that the impact of maternal ID on placental gene expression in mice is limited in scope and magnitude at mid-gestation. We provide strong evidence for IRE-based transcriptional and translational coordination of iron gene expression in the mouse placenta. Finally, we discover sexually dimorphic effects of maternal ID on placental gene expression, with more genes and pathways altered in male compared with female mouse placentas.
Project description:We used the rhesus monkey (Macaca mulatta) as our animal model for the current study with two goals: to characterize the changes in histology and gene expression from early to late gestation (prenatal uterine organogenesis) and to determine if there are effects of prenatal exposure to bisphenol A (BPA) on the developing female uterus. Pregnant rhesus monkeys carrying a female fetus (N=22) were divided into two experimental groups, based on gestational timing: 'early' (N=10) and 'late' (N=12). These groups were then equally sub-divided into control (unexposed) and BPA (exposed) groups (5 Early Control, 5 Early BPA-exposed, 6 Late Control and 6 Late BPA-exposed.) The BPA-exposed monkeys received a deuterated BPA (dBPA, CDN Isotopes, Quebec, Canada) fruit treat on a daily basis, at a dose of 400ug/kg/day). The dosing was aimed at achieving serum levels of BPA detected in adult human biomonitoring studies. The control animals received a vehicle control on a daily basis. The 'early' time period (mid-gestation) referred to gestational days 50-100, approximating the second trimester of human gestation. The fetal monkeys in the 'early' group were delivered via cesarean section on gestation day 100 and euthanized. Samples of maternal and fetal blood and amniotic fluid were obtained. Maternal and fetal weights were also recorded. The 'late' time period referred to gestational days 100-165, approximating the third trimester of human gestation. The fetal monkeys in the 'late' group were delivered vaginally and euthanized. There were five idiopathic stillbirths (2 Control, 3 BPA-exposed) in the late group. Samples of maternal and fetal blood and amniotic fluid were obtained. Maternal and fetal weights were also recorded. After delivery, the fetal uterus was excised and cut sagitally from fundus to cervix; one side was fixed for histological evaluation and the other half was frozen for analysis of gene expression by microarray. The stillbirths were excluded from the microarray.
Project description:Fetal Hypoglycemia Induced by Placental SLC2A3 RNA Inter-ference Alters Fetal Pancreas Development and Transcriptome at Mid-Gestation
Project description:Normal development in the brain requires temporal changes in gene expression. A better understanding of the genomics of the fetal brain during late gestation can help to improve our understanding of the molecular events that enable the newborn to survive extra-uterine life. The purpose of the present study is to model changes and coherence of gene expression in cerebral cortex, brainstem, hippocampus, and hypothalamus throughout the second half of gestation. We used the sheep as an animal model to identify co-expressed genes in different regions of the ovine fetal brain, from mid-gestation (80 days) to one day of postnatal life. In the ewe, gestation length varies from 142 to 152 days, with an average of 147 days. Using a newly-available ovine array and weighted gene co-expression network analysis (WGCNA), we tested the hypothesis that the resulting products of genes expressed in a similar pattern through the last stage of gestation in different brain regions are functionally related and could play an important role in the normal fetal development.
Project description:We detected a genome-wide differential gene enrichment between mid-trimester and term human placenta. Pathway analysis identified that cytokine-cytokine receptor interaction, NF-κB, and TNF are the leading pathways enriched in term placenta. Our analysis has provided the first-time characterization of the key players of human placental origin with molecular changes across pregnancy, which could drive human labor.
Project description:Normal development in the brain requires temporal changes in gene expression. A better understanding of the genomics of the fetal brain during late gestation can help to improve our understanding of the molecular events that enable the newborn to survive extra-uterine life. The purpose of the present study is to model changes and coherence of gene expression in cerebral cortex, brainstem, hippocampus, and hypothalamus throughout the second half of gestation. We used the sheep as an animal model to identify co-expressed genes in different regions of the ovine fetal brain, from mid-gestation (80 days) to one day of postnatal life. In the ewe, gestation length varies from 142 to 152 days, with an average of 147 days. Using a newly-available ovine array and weighted gene co-expression network analysis (WGCNA), we tested the hypothesis that the resulting products of genes expressed in a similar pattern through the last stage of gestation in different brain regions are functionally related and could play an important role in the normal fetal development. Tissues from cortex, brainstem, hippocampus and hypothalamus were collected from non treated fetuses at 80 (80d, n=4), 96M-bM-^@M-^S100 (100d, n=4), 120 (120d, n=4), 130 (130d, n=4), and 142M-bM-^@M-^S144 (145d, n=4) days of gestation and on the first (1d, n=4) day after delivery. Each group included one set of twin fetuses. None of the ewes showed any signs of impending labor.