scholarly journals SAT-LB131 Examination of Hepatic Gene Expression Following Developmental Exposure to Dieldrin in Trachemys Scripta and Discovery of a Novel Hepacivirus

2020 ◽  
Vol 4 (Supplement_1) ◽  
Author(s):  
Mara H O’Brien ◽  
Ian P Callard
Keyword(s):  
Gene Expression ◽  
Interleukin 1 ◽  
Endocrine Disrupting Compounds ◽  
Trachemys Scripta ◽  
Estrogen Signaling ◽  
Health Concern ◽  
Hepatic Gene Expression ◽  
In Ovo ◽  
Developmental Exposure ◽  
Impacted Site

Abstract The Massachusetts Military Reservation (MMR) is a Superfund site where ground water has been contaminated by a mixture of pollutants. Exposure to these chemicals is a public health concern and reproductive impairments have been observed in a population of turtles (Chrysemys picta) endemic to this site. We hypothesize that developmental exposure to endocrine disrupting compounds originating from the MMR might lead to abnormalities seen in adult animals. Upon examination of egg yolk from turtles at the impacted site, we found the presence of dieldrin and p,p’-DDE. Turtles from a reference site were also found to have p,p’-DDE present in the yolk. In order to investigate these chemicals in the laboratory we used a closely related turtle (Trachemys scripta) and applied vehicle, dieldrin, or p,p’-DDE to the eggshells. Absorption of p,p’-DDE through the eggshell was limited. Although there were variations in absorbance, we were able to achieve levels of dieldrin in the yolk similar to what was seen in animals from the impacted site. Following in ovo exposure to dieldrin, we used RNAseq to examine hepatic gene expression in neonates and found that several transcripts were repressed at least 1.5-fold in the dieldrin-treated animals. QPCR was carried out to confirm differences in gene expression. We found that hepatic gene expression (fold ± SEM) of Gamma-Butyrobetaine Hydroxylase 1 (Bbox1) was higher in vehicle-treated animals (1 ± 0.60) compared to dieldrin-treated animals (0.29 ± 0.12). Bbox1 catalyzes the last step in the L-carnitine biosynthetic pathway, which is necessary for mitochondrial beta-oxidation. Dieldrin-induced reduction in L-carnitine production may be a critical factor in adult reproductive function. Further, Protein-L-Isoaspartate (D-Aspartate) O-Methyltransferase Domain Containing Protein 1 (Pcmtd1) was higher (1± 0.76) in vehicle-treated animals compared to dieldrin-treated animals (0.13 ± 0.044), and DENN Domain Containing 5B (Dennd5b) was also found to be higher in vehicle-treated (1 ± 0.39) compared to dieldrin-treated (0.28 ± 0.10) turtles. We found that dieldrin exposure did not alter gene expression of Cytochrome p450 1a (Cyp1a) a marker of aryl hydrocarbon receptor signaling, or Vitellogenin 2 (Vtg2) a marker of estrogen signaling. In our RNAseq analysis we unexpectedly discovered a hepacivirus infecting T. scripta. In the dieldrin-treated group, we used QPCR to examine gene expression of potential markers of hepacivirus infection. Neither Interleukin 1 Beta (Il-1β), SMAD Family Member 6 (Smad6), C-C Motif Chemokine Ligand 5 (Ccl5), or TNF Receptor Superfamily Member 9 (Tnfrsf9) was found to differ in turtles carrying the virus, compared to non-infected animals. In conclusion, we found that developmental dieldrin exposure of T. scripta slightly reduces neonatal expression of several gene transcripts which may be correlated to adult reproductive fitness.

scholarly journals Persistent gene expression in mouse vagina exposed neonatally to diethylstilbestrol

2004 ◽  
Vol 32 (3) ◽  
pp. 663-677 ◽  
Author(s):  
S Miyagawa ◽  
A Suzuki ◽  
Y Katsu ◽  
M Kobayashi ◽  
M Goto ◽  
...  
Keyword(s):  
Gene Expression ◽  
Interleukin 1 ◽  
Expression Patterns ◽  
Laboratory Animals ◽  
Developmental Exposure ◽  
Cell Proliferation And Differentiation ◽  
Proliferation And Differentiation ◽  
Igf I ◽  
Phosphorylation Cascade ◽  
Insight Into

Developmental exposure to a synthetic estrogen, diethylstilbestrol (DES), induces carcinogenesis in human and laboratory animals. In mice, neonatal DES treatment induces persistent proliferation and keratinization of the vaginal epithelium, even in the absence of the ovaries, resulting in cancerous lesions later in life. To understand the mechanisms underlying this persistent cell proliferation and differentiation, we characterized the gene expression patterns in the neonatally DES-exposed mouse vagina using DNA microarray and real-time quantitative RT-PCR. We found that genes related to cellular signaling, which are candidates for mediating the persistent proliferation and differentiation, were altered, and genes related to the immune system were decreased in the neonatally DES-exposed mouse vagina. We also noted high expression of interleukin-1 (IL-1)-related genes accompanied by phosphorylation of JNK1. In addition, expression IGF-I and its binding proteins was modulated and led to phosphorylation of IGF-I receptor and Akt, which is one of the downstream factors of IGF-I signaling. This led us to characterize the expression as well as the phosphorylation status of IL-1 and IGF-I signaling pathway components which may activate the phosphorylation cascade in the vagina of mice exposed neonatally to DES. These findings give insight into persistent activation in the vagina of mice exposed neonatally to DES.

The Oral Intake of Organic Germanium, Ge-132, Elevates α-Tocopherol Levels in the Plas-ma and Modulates Hepatic Gene Expression Profiles to Promote Immune Activation in Mice

2014 ◽  
Vol 84 (3-4) ◽  
pp. 0183-0195 ◽  
Author(s):  
Takashi Nakamura ◽  
Tomoya Takeda ◽  
Yoshihiko Tokuji
Keyword(s):  
Gene Expression ◽  
Immune Activation ◽  
Expression Profiles ◽  
Water Soluble ◽  
Alpha Tocopherol ◽  
Hepatic Gene Expression ◽  
Tocopherol Concentration ◽  
Altered Expression ◽  
Atp Production ◽  
Transfer Protein

The common water-soluble organic germanium compound poly-trans-[(2-carboxyethyl) germasesquioxane] (Ge-132) exhibits activities related to immune responses and antioxidant induction. In this study, we evaluated the antioxidative effect of dietary Ge-132 in the plasma of mice. Male ICR mice (seven mice per group) received an AIN-76 diet with 0.05 % Ge-132; three groups received the Ge-132-containing diet for 0, 1 or 4 days. The plasma alpha-tocopherol (α-tocopherol) concentration increased from 6.85 to 9.60 μg/ml after 4 days of Ge-132 intake (p < 0.05). We evaluated the changes in hepatic gene expression related to antioxidative activity as well as in the entire expression profile after one day of Ge-132 intake, using DNA microarray technology. We identified 1,220 genes with altered expression levels greater than 1.5-fold (increased or decreased) as a result of Ge-132 intake, and α-tocopherol transfer protein (Ttpa) gene expression was increased 1.62-fold. Immune activation was identified as the category with the most changes (containing 60 Gene Ontology (GO) term biological processes (BPs), 41 genes) via functional clustering analysis of altered gene expression. Ge-132 affected genes in clusters related to ATP production (22 GO term BPs, 21 genes), lipid metabolism (4 GO term BPs, 38 genes) and apoptosis (5 GO term BPs). Many GO term BPs containing these categories were significantly affected by the Ge-132 intake. Oral Ge-132 intake may therefore have increased plasma α-tocopherol levels by up-regulating α-tocopherol transfer protein (Ttpa) gene expression.

Local mechanisms for acupoint sensitization in gall bladder meridian of foot shaoyang-a gene chip study

2019 ◽  
Vol 44 (2) ◽  
pp. 77-87
Author(s):  
Koichi Ishida ◽  
Liyue Qin ◽  
Ting Wang ◽  
Ying Lei ◽  
Weiwei Hu ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gall Bladder ◽  
Interleukin 1 ◽  
Gene Chip ◽  
Molecular Evidence ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
Bladder Meridian ◽  
Integrin Linked Kinase ◽  
Necrosis Factor

Acupuncture manipulations are clinically important to traditional Chinese medicine, yet the biological mechanisms have not been fully understood. This study aimed to investigate continuous stimulation-induced gene expression changes at stimulated and non-stimulated adjacent acupoints in the same meridian. Catgut embedding into acupoint (CEP) was conducted at acupoint Yanglingquan (gall bladder meridian of foot-shaoyang 34, GB34) of Sprague Dawley rats once or continuously for eight weeks, and gene expression changes at GB34 were assessed by gene chip array analysis 72 h after the last CEP treatment. A total of 688 genes exhibited opposite changes in expression between the two treatments, and 1,336 genes were regulated only by the eight-week CEP treatment. Ingenuity Pathway Analysis revealed that among these differentially regulated genes by one-time and eight-week CEP treatment, insulin-like growth factor-1 pathway and integrin-linked kinase pathway, and Wnt/~ catenin signaling pathway match the observed gene changes to predicted up/down regulation patterns. Upstream analysis further predicted six molecules, namely, tumor necrosis factor, interleukin 1~, interleukin la, kallikrein-related peptidase 5, protein kinase Ca, and catenin ~1. On the other hand, continuous eight-week CEP stimulation at acupoint Xuanzhong (GB39) caused similar changes in the expression of 32 genes at acupoints GB34 and Fengshi (GB31) on the same meridian. Taken together, our results provide the first molecular evidence for the local acupoints' mechanisms for acupoint sensitization theory, and implicate the existence of signaling pathways, either direct or indirect, between acupoints within the meridian GB.

scholarly journals Genome-wide gene expression changes in postpartum depression point towards an altered immune landscape

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Divya Mehta ◽  
Karen Grewen ◽  
Brenda Pearson ◽  
Shivangi Wani ◽  
Leanne Wallace ◽  
...  
Keyword(s):  
Gene Expression ◽  
Depressive Symptoms ◽  
Postpartum Depression ◽  
Expression Profiles ◽  
Depression Scale ◽  
Well Being ◽  
Health Concern ◽  
Genome Wide ◽  
A Genome ◽  
Genome Wide Gene Expression

AbstractMaternal postpartum depression (PPD) is a significant public health concern due to the severe negative impact on maternal and child health and well-being. In this study, we aimed to identify genes associated with PPD. To do this, we investigated genome-wide gene expression profiles of pregnant women during their third trimester of pregnancy and tested the association of gene expression with perinatal depressive symptoms. A total of 137 women from a cohort from the University of North Carolina, USA were assessed. The main phenotypes analysed were Edinburgh Postnatal Depression Scale (EPDS) scores at 2 months postpartum and PPD (binary yes/no) based on an EPDS cutoff of 10. Illumina NextSeq500/550 transcriptomic sequencing from whole blood was analysed using the edgeR package. We identified 71 genes significantly associated with postpartum depression scores at 2 months, after correction for multiple testing at 5% FDR. These included several interesting candidates including TNFRSF17, previously reported to be significantly upregulated in women with PPD and MMP8, a matrix metalloproteinase gene, associated with depression in a genome-wide association study. Functional annotation of differentially expressed genes revealed an enrichment of immune response-related biological processes. Additional analysis of genes associated with changes in depressive symptoms from recruitment to 2 months postpartum identified 66 genes significant at an FDR of 5%. Of these genes, 33 genes were also associated with depressive symptoms at 2 months postpartum. Comparing the results with previous studies, we observed that 15.4% of genes associated with PPD in this study overlapped with 700 core maternal genes that showed significant gene expression changes across multiple brain regions (P = 7.9e-05) and 29–53% of the genes were also associated with estradiol changes in a pharmacological model of depression (P values range = 1.2e-4–2.1e-14). In conclusion, we identified novel genes and validated genes previously associated with oestrogen sensitivity in PPD. These results point towards the role of an altered immune transcriptomic landscape as a vulnerability factor for PPD.

scholarly journals Early and late stage MPN patients show distinct gene expression profiles in CD34+ cells

2021 ◽  
Author(s):  
Julian Baumeister ◽  
Tiago Maié ◽  
Nicolas Chatain ◽  
Lin Gan ◽  
Barbora Weinbergerova ◽  
...  
Keyword(s):  
Gene Expression ◽  
Late Stage ◽  
Rna Splicing ◽  
Bone Marrow Cells ◽  
Myeloproliferative Neoplasms ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Primary Myelofibrosis ◽  
Estrogen Signaling ◽  
Therapeutic Modalities

AbstractMyeloproliferative neoplasms (MPN), comprising essential thrombocythemia (ET), polycythemia vera (PV), and primary myelofibrosis (PMF), are hematological disorders of the myeloid lineage characterized by hyperproliferation of mature blood cells. The prediction of the clinical course and progression remains difficult and new therapeutic modalities are required. We conducted a CD34+ gene expression study to identify signatures and potential biomarkers in the different MPN subtypes with the aim to improve treatment and prevent the transformation from the rather benign chronic state to a more malignant aggressive state. We report here on a systematic gene expression analysis (GEA) of CD34+ peripheral blood or bone marrow cells derived from 30 patients with MPN including all subtypes (ET (n = 6), PV (n = 11), PMF (n = 9), secondary MF (SMF; post-ET-/post-PV-MF; n = 4)) and six healthy donors. GEA revealed a variety of differentially regulated genes in the different MPN subtypes vs. controls, with a higher number in PMF/SMF (200/272 genes) than in ET/PV (132/121). PROGENγ analysis revealed significant induction of TNFα/NF-κB signaling (particularly in SMF) and reduction of estrogen signaling (PMF and SMF). Consistently, inflammatory GO terms were enriched in PMF/SMF, whereas RNA splicing–associated biological processes were downregulated in PMF. Differentially regulated genes that might be utilized as diagnostic/prognostic markers were identified, such as AREG, CYBB, DNTT, TIMD4, VCAM1, and S100 family members (S100A4/8/9/10/12). Additionally, 98 genes (including CLEC1B, CMTM5, CXCL8, DACH1, and RADX) were deregulated solely in SMF and may be used to predict progression from early to late stage MPN. Graphical abstract

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