Proteomics Profiling Reveals Lipid Metabolism Abnormalities During Oogenesis in Unexplained Recurrent Pregnancy Loss
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo Sapiens
SUBMITTER: 
Wei Sun
PROVIDER: PXD051475 | iProX | Tue Apr 16 00:00:00 BST 2024
REPOSITORIES: iProX
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Project description:Pregnancy loss is the most common complication of human pregnancy. Recurrent early pregnancy loss (REPL) has multiple etiologies, including endometrial dysregulation leading to “suboptimal” implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. We hypothesized that genes that gained novel expression in the endometria of mammals that evolved in the Eutherian stemlineage, coincident with the evolution of pregnancy, are likely essential for establishment and maintenance of normal pregnancy and are, therefore, good candidates for genes whose expression may be dysregulated in disorders such as REPL. To test this hypothesis, we took an evolutionary forward genomics approach to characterize gene expression profiles of midsecretory endometria from women with REPL associated with abnormal endometria based either on histology or molecular expression of cyclin E. We identified 58 genes that were differentially expressed (P<0.001) between women with out-of-phase histological dating vs normal histology, and 81 genes that were differentially expressed (P<0.001) between women with abnormally elevated cyclin E levels vs normal cyclin E. Remarkably, genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P=0.002 for histology, P=0.021 for cyclin E), as well as for immune and signaling pathways with essential roles in endometrial biology. Thus, our novel evolutionary-based forward genomics approach identified genes whose dysregulation during the mid-secretory phase likely contributes to the molecular etiologies of recurrent early pregnancy loss. Total RNA obtained from mid luteal phase endometrium (two replicates per biopsy) from women with recurrent early pregnancy loss (REPL). Endometrial gene expression levels were compared 1) between women with out-of-phase (n=10) and normal histological dating (n=22), 2) between women with abnormally elevated (n=9) and normal (n=23) cyclin E levels. For 5 additional women with abnormally high cyclin E levels, biopsy samples were collected before and after progesterone treatment to investigate the gene expression profiles in response to progesterone.
2014-12-06 | E-GEOD-63901 | biostudies-arrayexpress
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:The project aimed to determine proteomics changes in decidua from patients suffering from unexplained early recurrent pregnancy loss (RPL) compared to women undergoing elective abortions. Comparative proteomics analysis by label-free data-independent LC-MS/MS was performed on fresh frozen decidua tissues from 19 RPL patients and 10 controls. Samples from EPL patients were preselected to include only patients with 2 or more recurrent pregnancy losses (RPL), no previous live birth, gestational week from 6-10 weeks and excluded fetal chromosomal abnormalities. Control samples were from women without history of previous miscarriage, ectopic pregnancy or preterm delivery, with at least one live born child, at 6-10 gestational weeks and without fetal chromosomal abnormalities. Patients and controls had no significant differences regarding age (Median age RPL = 30; Median age Controls = 34; Mann–Whitney U-test p = 0.082). The mean gestational weak (GW) was 7.9±1.0 weeks in the RPL group and 8.3±1.2 weeks in the control group, without statistically significant difference between groups (Median GW RPL = 8; Median GW Controls = 8; Mann–Whitney U-test p = 0.361).
2024-06-12 | PXD048340 | Pride
Project description:The project aimed to determine proteomics changes in chorionic villi from patients suffering from unexplained early recurrent pregnancy loss (RPL) compared to women undergoing elective abortions. Comparative proteomics analysis by label-free data-independent LC-MS/MS was performed on fresh frozen chorionic villi from 13 RPL patients and 10 controls. Samples from EPL patients were preselected to include only patients with 2 or more recurrent pregnancy losses (RPL), no previous live birth, gestational week from 6-10 weeks and excluded fetal chromosomal abnormalities. Control samples were from women without history of previous miscarriage, ectopic pregnancy or preterm delivery, with at least one live born child, at 6-10 gestational weeks and without fetal chromosomal abnormalities. Patients and controls were between 24-44 years with no significant differences among groups regarding age (Median age RPL = 29; Median age Controls = 34; Mann–Whitney U-test p = 0.078). The mean gestational weak (GW) was 7.9±0.8 weeks in the RPL group and 8.3±1.2 weeks in the control group, without statistically significant difference between groups (Median GW RPL = 8; Median GW Controls = 8; Mann–Whitney U-test p = 0.484).
2024-08-27 | PXD048344 | Pride
Project description:This study sought to determine whether an endometrial gland specific transcriptome and splicing profile are altered in the window of implantation (days 21-23 of the menstrual cycle) in women with recurrent pregnancy loss. Our data provide a comprehensive catalogue of gene isoforms and relative exon usage in endometrial glands. The endometrial gland targets identified in this study could be used to identify a perturbed endometrium, isolate causes of recurrent pregnancy loss and develop targeted therapies in personalised medicine.
2021-09-23 | GSE183555 | GEO
Project description:Pregnancy loss is the most common complication of human pregnancy. Recurrent early pregnancy loss (REPL) has multiple etiologies, including endometrial dysregulation leading to “suboptimal” implantation. Although the implantation process is tightly regulated in Eutherian (placental) mammals, the molecular factors contributing to dysregulated endometrial gene expression patterns in women with REPL are largely unknown. We hypothesized that genes that gained novel expression in the endometria of mammals that evolved in the Eutherian stemlineage, coincident with the evolution of pregnancy, are likely essential for establishment and maintenance of normal pregnancy and are, therefore, good candidates for genes whose expression may be dysregulated in disorders such as REPL. To test this hypothesis, we took an evolutionary forward genomics approach to characterize gene expression profiles of midsecretory endometria from women with REPL associated with abnormal endometria based either on histology or molecular expression of cyclin E. We identified 58 genes that were differentially expressed (P<0.001) between women with out-of-phase histological dating vs normal histology, and 81 genes that were differentially expressed (P<0.001) between women with abnormally elevated cyclin E levels vs normal cyclin E. Remarkably, genes that were recruited into endometrial expression during the evolution of pregnancy in Eutherian mammals were significantly enriched for dysregulated genes (P=0.002 for histology, P=0.021 for cyclin E), as well as for immune and signaling pathways with essential roles in endometrial biology. Thus, our novel evolutionary-based forward genomics approach identified genes whose dysregulation during the mid-secretory phase likely contributes to the molecular etiologies of recurrent early pregnancy loss.
2014-12-06 | GSE63901 | GEO
Project description:The immune atlas of human deciduas with unexplained recurrent pregnancy loss
| PRJNA690775 | ENA
Project description:Polymorphonuclear myeloid-derived suppressor cell (PMN-MDSC) accumulate in maternal-fetal interface during pregnancy and play a role in maintenance of immune tolerance. Decreased PMN-MDSC is associated with pregnancy complications such as unexplained recurrent pregnancy loss (URPL). Whether PMN-MDSC function is different between normal pregnancy (NP) and URPL remains unexplored. Here we performed whole genome expression profile of 3 decidual PMN-MDSC from normal early pregnancy and 3 decidual PMN-MDSC from URPL. Total RNA were extracted. Cy5-labeled aRNA was hybridized and scanned on a G2505C Agilent Microarray Scanner with Agilent 0.1 XDR software. The gene expression pattern of the PMN-MDSC was significantly different between the NP group and the URPL group.
2020-06-30 | GSE139180 | GEO
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:Whole genome expression profile of human decidual PMN-MDSC in normal pregnancy and unexplained recurrent pregnancy loss
| PRJNA578703 | ENA