Metabolomics,Unknown,Transcriptomics,Genomics,Proteomics

Dataset Information

RNA-seq of estrogen (E2) induced changes of mRNA expression in early pregnant Sus scrofa endometrium

ABSTRACT: Maternal exposure to estrogens can induce long-term adverse effects in the offspring. This may be mediated through alterations in the endometrium affecting embryo-maternal communication as early as the preimplantational phase. Thus, we analyzed the effects of gestational estradiol-17β (E2) exposure on the endometrium. Two distinct low doses and a high dose (0.05, 10 and 1000 µg E2/kg body weight daily, respectively) were orally applied to sows from insemination until sampling at day 10 of pregnancy and compared to carrier-treated controls. RNA-sequencing revealed a dose-dependent increase of 14, 17 and 27 differentially expressed genes (DEG), respectively. Overall, the maternal E2 treatment perturbed gene expression of the endometrium, potentially altering the uterine histotroph.

INSTRUMENT(S): Illumina Genome Analyzer IIx

ORGANISM(S): Sus scrofa

SUBMITTER: Stefan Bauersachs

PROVIDER: E-MTAB-6242 | biostudies-arrayexpress |

REPOSITORIES: biostudies-arrayexpress

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Publications

Exposure of pregnant sows to low doses of estradiol-17β impacts on the transcriptome of the endometrium and the female preimplantation embryos†.

Flöter Veronika L VL Bauersachs Stefan S Fürst Rainer W RW Krebs Stefan S Blum Helmut H Reichenbach Myriam M Ulbrich Susanne E SE

Biology of reproduction 20190301 3

Maternal exposure to estrogens can induce long-term adverse effects in the offspring. The epigenetic programming may start as early as the period of preimplantation development. We analyzed the effects of gestational estradiol-17β (E2) exposure with two distinct low doses, corresponding to the acceptable daily intake "ADI" and close to the no-observed-effect level "NOEL", and a high dose (0.05, 10, and 1000 μg E2/kg body weight daily, respectively). The E2 doses were orally applied to sows from ...[more]

PMID: 30260370

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Project description:Eutopic endometrium in endometriosis has molecular evidence of resistance to progesterone (P4) and activation of the PKA pathway in the stromal compartment. To investigate global and temporal responses of eutopic endometrium to P4, we compared early (6-h), intermediate (48-h), and late (14-day) transcriptomes, signaling pathways, and networks of human endometrial stromal fibroblasts (hESFs) from women with endometriosis (hESFendo) to hESFs from women without endometriosis (hESFnonendo). Endometrial biopsy samples were obtained from subjects with and without mild peritoneal endometriosis (n = 4 per group), and hESFs were isolated and treated with P4 (1 μM) plus estradiol (E2) (10 nM), E2 alone (10 nM), or vehicle for up to 14 days. Total RNA was subjected to microarray analysis using a Gene 1.0 ST (Affymetrix) platform and analyzed by using bioinformatic algorithms, and data were validated by quantitative real-time PCR and ELISA. Results revealed unique kinetic expression of specific genes and unique pathways, distinct biological and molecular processes, and signaling pathways and networks during the early, intermediate, and late responses to P4 in both hESFnonendo and hESFendo, although a blunted response to P4 was observed in the latter. The normal response of hESF to P4 involves a tightly regulated kinetic cascade involving key components in the P4 receptor and MAPK signaling pathways that results in inhibition of E2-mediated proliferation and eventual differentiation to the decidual phenotype, but this was not established in the hESFendo early response to P4. The abnormal response of this cell type to P4 may contribute to compromised embryonic implantation and infertility in women with endometriosis. We compared early (6-h), intermediate (48-h), and late (14-day) in vitro whole-genome responses of hESF from women with endometriosis (hESFendo) to hESF from women without endometriosis (hESFnonendo) treated with P4 plus E2 (E2P4), E2 alone, or vehicle alone. Using this experimental paradigm, the data demonstrate unique phenotypes, gene expression processes, biochemical and signaling pathways, and networks suggestive of early, intermediate, and late responses of hESFnonendo and hESFendo to P4, giving insights into the complexity of events occurring normally in response to P4 and in the setting of endometriosis.

Project description:Gene transcription mediated by RNA polymerase II (pol-II) is a key step in gene expression. The dynamics of pol-II moving along the transcribed region influences the rate and timing of gene expression. In this work we present a probabilistic model of transcription dynamics which is fitted to pol-II occupancy time course data measured using ChIP-Seq. The model can be used to estimate transcription speed and to infer the temporal pol-II activity profile at the gene promoter. Model parameters are determined using either maximum likelihood estimation or via Bayesian inference using Markov chain Monte Carlo sampling. The Bayesian approach provides confidence intervals for parameter estimates and allows the use of priors that capture domain knowledge, e.g. the expected range of transcription speeds, based on previous experiments. The model describes the movement of pol-II down the gene body and can be used to identify the time of induction for transcriptionally engaged genes. By clustering the inferred promoter activity time profiles, we are able to determine which genes respond quickly to stimuli and group genes that share activity profiles and may therefore be co-regulated. We apply our methodology to biological data obtained using ChIP-seq to measure pol-II occupancy genome-wide when MCF-7 human breast cancer cells are treated with estradiol (E2). The transcription speeds we obtain agree with those obtained previously for smaller numbers of genes with the advantage that our approach can be applied genome- wide. We validate the biological significance of the pol-II promoter activity clusters by investigating cluster-specific transcription factor binding patterns and determining canonical pathway enrichment. MCF-7 cells were mock treated or with 10nM 17b-E2 to seven time points (5', 10', 20', 40', 80', 160', 320') Genome-wide identification of RNA polymerase II (RNAPII) occupancy at different time points following E2 induction of MCF-7 cells

Dataset Information

RNA-seq of estrogen (E2) induced changes of mRNA expression in early pregnant Sus scrofa endometrium

Publications

Exposure of pregnant sows to low doses of estradiol-17β impacts on the transcriptome of the endometrium and the female preimplantation embryos†.

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