Loss of endometrial plasticity in recurrent pregnancy loss
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Jan Brosens
PROVIDER: E-GEOD-65102 | biostudies-arrayexpress |
REPOSITORIES: biostudies-arrayexpress
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Project description:In order to try and identify characteristics of gene expression in the endometrium of women suffering infertility or recurrenty miscarriage, we performed RNAseq on endometrial pipelle biopsies from 20 women. The endometrial transcriptome in the mid-luteal phase of the cycle (window of implantation) is highly divergent in women suffering infertility or miscarriages. 20 mid-luteal endometrial biopsies were analysed from infertile women and patients suffering recurrent pregnancy loss.
2015-09-16 | E-GEOD-65099 | biostudies-arrayexpress
Project description:Decidual transformation of the human endometrium is not dependent on embryo implantation. Instead, this process is initiated during the mid-luteal phase of each cycle in response to the postovulatory rise in progesterone and increasing endometrial cAMP levels. Consequently, decidualization is a reiterative process directly linked to cyclic activation of mesenchymal stem cells (MSCs) and subsequent differentiation into mature stromal cells in regenerating endometrium. We reasoned that aberrant remodeling of the HESC epigenome would disrupt decidualization in RPL patients and account for the functional memory of HESCs in culture. To explore this possibility, we performed MeDIP-seq, which involves immunoprecipitation of DNA with a 5-methylcytosine antibody followed by deep sequencing, on primary HESC cultures established from four RPL patients and four control subjects. Eight samples were analyzed: derived from four control and four recurrent pregnancy loss (RPL) patient cultures.
2015-09-16 | E-GEOD-65100 | biostudies-arrayexpress
Project description:Implantation is dependent on synchronized interactions between the conceptus and surrounding decidual cells but the involvement of clock genes in this process is not well understood. Circadian oscillations are predicated on transcriptional-translational feedback loops, which balance the activities of the transcriptional activators CLOCK and BMAL1 and repressors encoded by PER and CRY genes. Here we show that loss of PER2 expression silences circadian oscillations in decidualizing human endometrial stromal cells (HESCs). Downregulation was preceded by reduced CLOCK binding to a noncanonical E-box enhancer in the PER2 promoter and occurred between 12 - 24 h after exposure to a deciduogenic stimulus. RNA sequencing revealed that premature inhibition of PER2 by siRNA knockdown leads to a grossly disorganised decidual response. Gene ontology analysis highlighted a preponderance of cell cycle regulators amongst the 1,121 genes perturbed upon PER2 knockdown. Congruently, PER2 inhibition abrogated mitotic expansion of differentiating HESCs by inducing cell cycle block at G2/M. Analysis of mid-luteal endometrial biopsies revealed an inverse correlation between PER2 transcript levels and the number of miscarriages in women suffering reproductive failure. Thus, PER2 synchronizes mitotic expansion of HESCs with a periodic decidual gene expression; uncoupling of these events may cause persistent pregnancy failure. Endometrial mRNA profiles of paired control (siRNA-NT) and siRNA-PER2 were generated by deep sequencing, in triplicate using Illumina
2015-09-16 | E-GEOD-62854 | biostudies-arrayexpress
Project description:The purpose of this study was to compare and contrast the expression of mRNA sequences in samples of endometrial glandular epithelium taken at discrete points in the menstrual cycle of healthy female subjects. This study was approved by the Erasme Hospital Ethics Committee and was conducted at the Pfizer Clinical Research Unit at the Erasme hospital, Brussels. The study was conducted in accordance with the Declaration of Helsinki on Ethical Principals for Medical Research Involving Human Subjects, adopted by the General Assembly of the World Medical Association (1996). In addition, the study was conducted in accordance with the protocol, the principles of the International Conference on Harmonization guideline on Good Clinical Practice and applicable local regulatory requirements and laws. Written informed consent was obtained from all participants in this study prior to screen. Female healthy subjects were between 20 and 39 years of age and had a regular menstrual cycle. A total of 23 endometrial biopsies were taken from women at different stages of their menstrual cycle (mid & late follicular; early & mid luteal phases) by pipelle catheter. Glandular epithelium was laser capture microdissected and total RNA was purified, labelled and hybridized to Affymetrix HG-U133 Plus 2 chips using standard protocols. The resulting data were subjected to a principal component analysis and assessment by a proprietary methodology, the causal reasoning engine. Using this analysis we describe new progesterone marker genes and a robust methodology which may be useful for identifying endometrial pharmacological response genes or diagnostic disease markers. A single sample was taken from each of 20 human subjects at time points across the menstrual cycle.
2011-08-31 | E-GEOD-29981 | biostudies-arrayexpress
Project description:Endometriosis is associated with aberrant gene expression in the eutopic endometrium of women with disease. To determine if the development of endometriotic lesions directly impacts eutopic endometrial gene expression, we sequentially analyzed the eutopic endometrium across the time course of disease progression in a baboon model of induced disease. Endometriosis was induced in baboons by intraperitoneal inoculation of autologous menstrual endometrium. Eutopic endometria were collected at 9-11 days postovulation) in five time points: 1, 3, 6-7, 10-12, and 15-16 months after disease induction and compared with tissue from disease-free baboons. We used microarrays to identify differentially expressed genes between time points. Sequential analysis of the same animals during disease progression demonstrated an early disease insult and a transitory dominance of an estrogenic phenotype. However, as the disease progressed, a progesterone-resistant phenotype became evident. Endometriosis was experimentally induced in Papio anubis female baboons (n = 4) by intraperitoneal inoculation with menstrual endometrium on two consecutive menstrual cycles. Baboons with spontaneous endometriosis (n = 2) were also included in this study with an unknown duration of disease. Control endometrium was similarly harvested from animals (n = 4) with no previous surgeries and with no visible disease. The progression of disease was monitored in each animal by consecutive laparoscopies and video recording at 1 (n = 2), 3 (n = 4), 6-7 (n = 4), 10-12, (n = 4), and 15-16 (n = 3) months after inoculation during a window of 9-11 days postovulation. Eutopic endometrial tissues were harvested and were snap frozen in liquid nitrogen for RNA extraction. Additionally, menstrual endometrium was harvested on Days 1-2 of menses using a Unimar Pipelle (Cooper Surgical Inc., Shelton, CT) immediately prior to laparoscopy. Blood samples were collected daily from days 7 through 16 postmenstruation of menstrual cycles.
2015-08-27 | E-GEOD-72428 | biostudies-arrayexpress
Project description:Research question: What are the proteomic and phosphoproteomic differences between the endometrium of women with recurrent pregnancy loss (RPL) and healthy control women during the proliferative (P) and secretory (S) phases of the menstrual cycle? Design: The present study collected a total of 54 endometrial samples during either P or S phases from women with RPL (n = 28) or healthy control (n = 26). Comprehensive proteomic and phosphoproteomic analyses were conducted using label-free liquid chromatography-tandem mass spectrometry (n = 44) and verified through western blotting (n = 10). Three comparison groups were established, including the total RPL endometrium compared to the total control (R/C), proliferating endometrium compared to control (RP/CP), and secretory endometrium compared to control (RS/CS). Results: Differentially expressed proteins (DEPs) and differentially phosphorylated proteins (DPPs) were respectively identified in the three comparison groups. Combining pathway enrichment, network analysis, and soft clustering analysis, we identified the insulin/cyclic nucleotide signaling pathway and AMPK/mTOR signaling pathway as the major contributors to the aberration of RPL endometrium. Western blotting verified altered expression of four proteins, including PRKAR1B, ADCY3, PRKAA2, and LPIN2.Conclusions: This exploratory study provides insights into the differentiated protein expression and phosphorylation profiles of RPL endometrium in both P and S phases. The results highlight potential proteins associated with RPL pathogenesis that may serve as potential indicators for RPL. The findings contribute to the identification of potential targets for RPL treatment as well as the pathogenesis of RPL.
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Project description:Transcriptome profile of receptive phase endometrium among infertile women with recurrent implantation failure (RIF) in two different endometrial preparation protocols for FET was analyzed: natural cycle (NC-FET) vs. artificial cycle (AC-FET). Fifteen endometrial biopsy samples were obtained: women with unexplained RIF (n = 5) in natural cycles for FET (NC-FET), women with unexplained RIF undergoing artificial endometrial preparation (n = 5) for FET (AC-FET), and healthy women (n = 5) with proven fertility in natural cycles (NC-FC) (Control group). All endometrial biopsies were obtained during the mid-secretory phase, at the time of ‘window of implantation’.
2016-01-15 | E-MTAB-3655 | biostudies-arrayexpress
Project description:Transcriptome profile of receptive phase endometrium among infertile women with recurrent implantation failure (RIF) in two different endometrial preparation protocols for FET was analyzed: natural cycle (NC-FET) vs. artificial cycle (AC-FET). Fifteen endometrial biopsy samples were obtained: women with unexplained RIF (n = 5) in natural cycles for FET (NC-FET), women with unexplained RIF undergoing artificial endometrial preparation (n = 5) for FET (AC-FET), and healthy women (n = 5) with proven fertility in natural cycles (NC-FC) (Control group). All endometrial biopsies were obtained during the mid-secretory phase, at the time of ‘window of implantation’.
2015-10-28 | E-MTAB-3713 | biostudies-arrayexpress
Project description:Endometrial cancer (EC) is one of the most frequently diagnosed gynecological cancers worldwide, and its prevalence has increased by more than 50% over the last two decades. Despite the understanding of the major signaling pathways driving the growth and metastasis of EC cells, clinical trials targeting these signaling pathways in human patients have reported poor outcomes. Heterogeneous nature of EC is suspected to be one of the key reasons for the failure of targeted therapies. However, no study so far has explored EC heterogeneity within the same patient at the proteomic level. In this study, we isolated proteins from tumor tissue samples obtained from different sites of EC from individual patients (~2-4 samples/patient). We then performed a SWATH-based comparative proteomic analysis, using liquid chromatography-tandem mass spectrometry (LC-MS/MS), to profile the protein content of different areas within EC tissue. Our results highlighted an average of 1424 unique proteins in 20 patient-derived EC tissues with a confidence corresponding to a false discovery rate below 1%. We have identified protein biomarkers that differentiate between premenopausal vs postmenopausal cancer, macroscopic vs microscopic tumor, and more vs less invasive cancer, and DNA mismatch repair defective vs intact tumor. Furthermore, the data revealed a list of unique proteins that, for the same patient, exist only in a single EC location but are not present in other locations within the same tumor. Overall, our proteomic analysis highlighted that tumor tissue samples collected from different sites of EC within the same patient can harbor diverse protein profiles. Importantly, this study sets the foundation for further investigations into the mechanisms of endometrial heterogeneity and some of the proteins identified here may represent potential novel EC drug targets.
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