Dataset Information

Divergent endometrial inflammatory cytokine expression at peri-implantation period and after the stimulation by copper intrauterine device.

ABSTRACT: Endometrial inflammation has contradictory effects. The one occurring at peri-implantation period is favourable for embryo implantation, whereas the other occurring after the stimulation by copper intrauterine device (Cu-IUD) prevents from embryo implantation. In this study, 8 week female ICR mice were used to investigate the endometrial inflammation, in which they were at proestrus stage (Group 1), at peri-implantation period (Group 2), and had a copper wire implanted into right uterine horn (Group 3). Cytokine array revealed that two cytokines were highly expressed in Group 2 and Group 3 as compared with Group 1, and seven cytokines, including tumour necrosis factor α (TNF-α), had selectively strong expression in Group 3. Immunohistochemistry demonstrated prominent TNF-α staining on the endometrium after Cu-IUD stimulation, and in vitro culture of human endometrial glandular cells with Cu induced TNF-α secretion. The increased TNF-α concentration enhanced in vitro THP-1 cells chemotaxis, and reduced embryo implantation rates. These results suggest that inflammatory cytokine profiles of endometrium are different between those at peri-implantation period and after Cu-IUD stimulation, and TNF-α is the one with selectively strong expression in the latter. It might account for the contradictory biological effects of endometrial inflammation.

SUBMITTER: Chou CH

PROVIDER: S-EPMC4606814 | biostudies-other | 2015

REPOSITORIES: biostudies-other

ACCESS DATA

Similar Datasets

Project description:The contraceptive effectiveness of intrauterine devices has been attributed in part to effects of a foreign body reaction on the endometrium. We performed this study to identify compare the effects on the endometrial transcriptome of intrauterine devices and combined oral contraceptives, to better understand their mechanisms of action. We collected endometrial and cervical biopsies from women using the levonorgestrel-intrauterine device, copper intrauterine device or levonorgestrel-containing combined oral contraceptives, and from women not using contraceptives (control group). Transcriptional profiling was performed with Affymetrix arrays, Principal Component Analysis and the bioconductor package limma. Pathway analysis was performed using EnrichR and Reactome 2016. In endometrial samples from copper intrauterine device users (n=13), there were no genes with statistically significant differential expression compared to controls (n=11), whereas in levonorgestrel-intrauterine device users (n=11), 2509 genes were significantly dysregulated and mapped onto several immune and inflammatory pathways. In combined oral contraceptive users (n=12), 133 genes were significantly dysregulated and mapped predominantly onto pathways involving regulation of metal ions. Both levonorgestrel-intrauterine device and combined oral contraceptive use were associated with significant downregulation of members of the metallothionein gene family. In cervical samples, none of the groups showed statistically significant differential gene expression compared to controls. In conclusion, hormonal and copper intrauterine devices differ significantly in their effects on the endometrial transcriptome, with endometrium from copper intrauterine device users being indistinguishable from luteal phase endometrium. These results suggest that the contraceptive mechanisms of intrauterine devices are unlikely to rely on a common pathway involving a foreign body reaction in the endometrium.

Project description:Exposure to maternal obesity in utero is associated with marked developmental effects in offspring that may not be evident until adulthood. Mechanisms regulating the programming effects of maternal obesity on fetal development have been reported, but little is known about how maternal obesity affects the earliest periods of embryonic development. This work explored how obesity influences endometrial gene expression during the peri-implantation period using a sheep model. Ewes were assigned randomly to diets that produced an obese state or maintained a lean state. After 4 mo, obese and lean ewes were bred and then euthanized at day 14 post-breeding. The uterus was excised, conceptuses were flushed, and endometrial tissue was collected. Isolated RNA from endometrial tissues (n = 6 ewes/treatment) were sequenced using an Illumina-based platform. Reads were mapped to the Ovis aries genome (Oar_4.0). Differential gene expression was determined, and results were filtered (false discovery rate ≤ 0.05 and ≥2-fold change, ≥0.2 reads/kilobase/million reads). Differentially expressed genes (DEGs) were identified (n = 699), with 171 downregulated and 498 upregulated in obese vs. lean endometrium, respectively. The most pronounced gene ontology categories identified were cellular process, metabolic process, and biological regulation. Enrichments were detected within the DEGs for genes involved with immune system processes, negative regulation of apoptosis, cell growth, and cell adhesion. A literature search revealed that 125 DEGs were associated with either the trophoblast lineage or the placenta. Genes within this grouping were involved with wingless/integrated signaling, angiogenesis, and integrin signaling. In summary, these data indicate that the peri-implantation endometrium is responsive to maternal obesity. Transcript profile analyses suggest that the endometrial immune response, adhesion, and angiogenesis may be especially susceptible to obesity. Thus, alterations in uterine transcript profiles during early embryogenesis may be a mechanism responsible for developmental programming following maternal obesity exposure in utero.

Dataset Information

Divergent endometrial inflammatory cytokine expression at peri-implantation period and after the stimulation by copper intrauterine device.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets