The transition of regularly cycling endometrium from the proliferative or Estrogen-dominant phase of the menstrual cycle to the Progesterone-dominant Early and Mid Secretory phases requires wide-spread changes in gene expression that shift the endometrium from a proliferative capacity to a differentiated 'decidual' phenotype in preparation for implantation. This process appears delayed in women with severe endometriosis, suggestive of a progesterone resistant endometrium in this disease.
Gene expression analysis of endometrium reveals progesterone resistance and candidate susceptibility genes in women with endometriosis.
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View SamplesDecidualization is a critical process for embryo implatation during which uterine stromal fibroblasts are transformed into large, epithelioid-like decidual cell. NOTCH1 is recepotor of Notch signaling that plays important roles for cell-cell communication, which involves gene regulatory mechanisms that control multiple cellular differentiation processes during embryonic and adult life.
Decreased Notch pathway signaling in the endometrium of women with endometriosis impairs decidualization.
Cell line
View SamplesAlthough the function of COUP-TFII in uterine decidualization has been described in mice, its role in the human uterus remains unknown.To interrogate the role of COUP-TFII in human endometrial function, we utilized a siRNA-mediated loss of function approach in primary human endometrial stromal cells.
COUP-TFII regulates human endometrial stromal genes involved in inflammation.
Specimen part
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Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
Specimen part
View SamplesGestational diabetes mellitus (GDM) affects approximately 18% of pregnancies in the United States and increases the risk of adverse health outcomes in the offspring. These adult disease propensities may be set by anatomical and molecular alterations in the placenta associated with GDM. To assess the mechanistic aspects of fetal programming, we measured genome-wide methylation (Infinium HumanMethylation450 Beadchips) and expression (Affymetrix Transcriptome Microarrays) in placental tissue of 41 GDM cases and 41 matched pregnancies without maternal complications from the Harvard Epigenetic Birth Cohort. Specific transcriptional and epigenetic perturbations associated with GDM status included alterations in the major histocompatibility complex (MHC) region, which were validated in an independent cohort, the Rhode Island Child Health Study. Gene ontology enrichment among gene regulation influenced by GDM revealed an over-representation of immune response pathways among differential expression, reflecting these coordinated changes in the MHC region. Our study represents the largest investigation of transcriptomic and methylomic differences associated with GDM, providing comprehensive insight into the molecular basis of GDM induced fetal (re)programming.
Epigenome-wide and transcriptome-wide analyses reveal gestational diabetes is associated with alterations in the human leukocyte antigen complex.
Specimen part
View SamplesTo examine the possibility that biochemical or molecular signatures of endometrium may prove to be more useful, we have investigated whole genome molecular phenotyping (54,600 genes/ESTs) of this tissue sampled across the cycle in 28 normo-ovulatory women, using high-density oligonucleotide microarrays. The results demonstrate that endometrial samples obtained by two different sampling techniques (biopsy and curetting hysterectomy specimens) from subjects who are as normal as possible in a human study and 4 including those with unknown histology, can be classified by their molecular signatures and correspond to known phases of the menstrual cycle with identical results using two independent analytical methods. Also, the results enable global identification of biological processes and molecular mechanisms that occur dynamically in the endometrium in the changing steroid hormone milieu across the menstrual cycle in normo-ovulatory women. The results underscore the potential of gene expression profiling for developing molecular diagnostics of endometrial normalcy and abnormalities and identifying molecular targets for therapeutic purposes in endometrial disorders.
Molecular phenotyping of human endometrium distinguishes menstrual cycle phases and underlying biological processes in normo-ovulatory women.
Age
View SamplesArid1a has a critical role for modulating epithelial proliferation which is a critical requisite for fertility
ARID1A Is Essential for Endometrial Function during Early Pregnancy.
Sex, Specimen part
View SamplesThe transcriptional profile of A673 parental and SP-2509 Drug resistant cells treated with DMSO and SP-2509 (2uM 48hrs) Overall design: A673 parental and SP-2509 Drug resistant cells treated with DMSO and SP-2509 (2uM 48hrs)
Ewing sarcoma resistance to SP-2509 is not mediated through KDM1A/LSD1 mutation.
Treatment, Subject
View SamplesThe transcriptional profile of A673 parental, and SP-2509 drug resistant washout cells (4 and 6 months) Overall design: Following generation of A673 SP-2509 drug resistant cells (chronic exposure for 7 months), drug was withdrawn with cell pellets collected 4 and 6 months after removal.
Ewing sarcoma resistance to SP-2509 is not mediated through KDM1A/LSD1 mutation.
Disease, Treatment, Subject
View SamplesThis SuperSeries is composed of the SubSeries listed below.
Sparstolonin B inhibits pro-angiogenic functions and blocks cell cycle progression in endothelial cells.
Specimen part, Treatment
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