Differences in gene expression of eutopic endometrium from healthy women and endometriosis patients

Objective The aim of the present study was to analyze the expression of the CD63, S100A6, and GNB2L1genes, which participate in mechanisms related to the complex pathophysiology of endometriosis. Methods A case-control study was conducted with 40 women who were diagnosed with endometriosis, and 15 fertile and healthy women. Paired samples of eutopic endometrium and endometriotic lesions (peritoneal and ovarian endometriotic implants) were obtained from the women with endometriosis in the proliferative (n = 20) or secretory phases (n = 20) of the menstrual cycle. As controls, paired endometrial biopsy samples were collected from the healthy women in the proliferative (n = 15) and secretory (n = 15) phases of the same menstrual cycle. We analyzed the expression levels of the CD63, S100A6, and GNB2L1 genes by real-time polymerase chain reaction. Results An increase in CD63, S100A6, and GNB2L1 gene transcript levels was observed in the ectopic implants compared with the eutopic endometrium of the women with and without endometriosis, regardless of the phase of the menstrual cycle. Conclusion These findings suggest that the CD63, S100A6, and GNB2L1 genes may be involved in the pathogenesis of endometriosis, since they participate in mechanisms such as inhibition of apoptosis, angiogenesis and cell proliferation, which lead to the loss of cell homeostasis in the ectopic endometrium, thus contributing to the implantation and survival of the tissue in the extrauterine environment.

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Is gene expression among women with rheumatoid arthritis dysregulated during a postpartum flare?

Arthritis Research & Therapy ◽

10.1186/s13075-021-02418-w ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Matthew Wright ◽

Mette K. Smed ◽

J. Lee Nelson ◽

Jørn Olsen ◽

Merete L. Hetland ◽

...

Keyword(s):

Rheumatoid Arthritis ◽

Gene Expression ◽

Disease Activity ◽

Activity Index ◽

Expression Profiles ◽

Expression Patterns ◽

Time Frame ◽

Differentially Expressed ◽

Healthy Women ◽

Immune Related Genes

Abstract Background To evaluate our hypotheses that, when rheumatoid arthritis (RA) flares postpartum, gene expression patterns are altered compared to (a) healthy women, (b) RA women whose disease activity is low or in remission postpartum, and (c) pre-pregnancy expression profiles. Methods Twelve women with RA and five healthy women were included in this pilot study. RA disease activity and postpartum flare were assessed using the Clinical Disease Activity Index (CDAI). Total RNA from frozen whole blood was used for RNA sequencing. Differential gene expression within the same women (within-group) over time, i.e., postpartum vs. third trimester (T3) or pre-pregnancy (T0), were examined, using a significance threshold of q < 0.05 and fold-change ≥ 2. Results Nine of the women with RA experienced a flare postpartum (RAFlare), while three had low disease activity or were in remission (RANoFlare) during that time frame. Numerous immune-related genes were differentially expressed postpartum (vs. T3) during a flare. Fold-changes in expression from T3 to postpartum were mostly comparable between the RAFlare and healthy groups. At 3 months postpartum, compared to healthy women, several genes were significantly differentially expressed only among the RAFlare women, and not among the RANoFlare women. Some of these genes were among those whose “normal” expression was significantly modulated postpartum, and the postpartum expression patterns were significantly altered during the RA flare. There were also some genes that were significantly differentially expressed in RAFlare compared to both healthy and RANoFlare women, even though their expression was not significantly modulated postpartum. Furthermore, while postpartum expression profiles were similar to those at pre-pregnancy among healthy women, significant differences were found between those time points among the RAFlare women. Conclusions The large majority of gene expression changes between T3 and 3 months postpartum among RA women who flared postpartum reflected normal postpartum changes also seen among healthy women. Nonetheless, during a postpartum flare, a set of immune-related genes showed dysregulated expression compared to healthy women and women with RA whose disease activity was low or in remission during the same time frame, while other genes demonstrated significant differences in expression compared to RA pre-pregnancy levels.

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A distinctive epigenetic ageing profile in human granulosa cells

Human Reproduction ◽

10.1093/humrep/deaa071 ◽

2020 ◽

Vol 35 (6) ◽

pp. 1332-1345

Author(s):

K W Olsen ◽

J Castillo-Fernandez ◽

A Zedeler ◽

N C Freiesleben ◽

M Bungum ◽

...

Keyword(s):

Gene Expression ◽

Granulosa Cells ◽

Ovarian Stimulation ◽

Collaborative Study ◽

Somatic Cells ◽

Chronological Age ◽

Methylation Array ◽

Healthy Women ◽

Age Related ◽

A Genome

Abstract STUDY QUESTION Does women’s age affect the DNA methylation (DNAm) profile differently in mural granulosa cells (MGCs) from other somatic cells? SUMMARY ANSWER Accumulation of epimutations by age and a higher number of age-related differentially methylated regions (DMR) in MGCs were found compared to leukocytes from the same woman, suggesting that the MGCs have a distinctive epigenetic profile. WHAT IS KNOWN ALREADY The mechanisms underlying the decline in women’s fertility from the mid-30s remain to be fully elucidated. The DNAm age of many healthy tissues changes predictably with and follows chronological age, but DNAm age in some reproductive tissues has been shown to depart from chronological age (older: endometrium; younger: cumulus cells, spermatozoa). STUDY DESIGN, SIZE, DURATION This study is a multicenter cohort study based on retrospective analysis of prospectively collected data and material derived from healthy women undergoing IVF or ICSI treatment following ovarian stimulation with antagonist protocol. One hundred and nineteen women were included from September 2016 to June 2018 from four clinics in Denmark and Sweden. PARTICIPANTS/MATERIALS, SETTING, METHODS Blood samples were obtained from 118 healthy women with varying ovarian reserve status. MGCs were collected from 63 of the 119 women by isolation from pooled follicles immediately after oocyte retrieval. DNA from leukocytes and MGCs was extracted and analysed with a genome-wide methylation array. Data from the methylation array were processed using the ENmix package. Subsequently, DNAm age was calculated using established and tailored age predictors and DMRs were analysed with the DMRcate package. MAIN RESULTS AND ROLE OF CHANCE Using established age predictors, DNAm age in MGCs was found to be considerable younger and constant (average: 2.7 years) compared to chronological age (average: 33.9 years). A Granulosa Cell clock able to predict the age of both MGCs (average: 32.4 years) and leukocytes (average: 38.8 years) was successfully developed. MGCs differed from leukocytes in having a higher number of epimutations (P = 0.003) but predicted telomere lengths unaffected by age (Pearson’s correlation coefficient = −0.1, P = 0.47). DMRs associated with age (age-DMRs) were identified in MGCs (n = 335) and in leukocytes (n = 1) with a significant enrichment in MGCs for genes involved in RNA processing (45 genes, P = 3.96 × 10−08) and gene expression (152 genes, P = 2.3 × 10−06). The top age-DMRs included the metastable epiallele VTRNA2-1, the DNAm regulator ZFP57 and the anti-Müllerian hormone (AMH) gene. The apparent discordance between different epigenetic measures of age in MGCs suggests that they reflect difference stages in the MGC life cycle. LARGE SCALE DATA N/A. LIMITATIONS, REASONS FOR CAUTION No gene expression data were available to associate with the epigenetic findings. The MGCs are collected during ovarian stimulation, which may influence DNAm; however, no correlation between FSH dose and number of epimutations was found. WIDER IMPLICATIONS OF THE FINDINGS Our findings underline that the somatic compartment of the follicle follows a different methylation trajectory with age than other somatic cells. The higher number of epimutations and age-DMRs in MGCs suggest that their function is affected by age. STUDY FUNDING/COMPETING INTEREST(S) This project is part of ReproUnion collaborative study, co-financed by the European Union, Interreg V ÖKS, the Danish National Research Foundation and the European Research Council. The authors declare no conflict of interest.

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Gene expression profiles of breast biopsies from healthy women identify a group with claudin-low features

BMC Medical Genomics ◽

10.1186/1755-8794-4-77 ◽

2011 ◽

Vol 4 (1) ◽

Cited By ~ 28

Author(s):

Vilde D Haakensen ◽

Ole Christian Lingjærde ◽

Torben Lüders ◽

Margit Riis ◽

Aleix Prat ◽

...

Keyword(s):

Gene Expression ◽

Expression Profiles ◽

Gene Expression Profiles ◽

Healthy Women

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Each pregnancy linearly changes immune gene expression in the blood of healthy women compared with breast cancer patients

Clinical Epidemiology ◽

10.2147/clep.s163208 ◽

2018 ◽

Vol Volume 10 ◽

pp. 931-940 ◽

Cited By ~ 1

Author(s):

Eiliv Lund ◽

Aurelie Nakamura ◽

Igor Snapkov ◽

Jean-Christophe Thalabard ◽

Karina Standahl Olsen ◽

...

Keyword(s):

Breast Cancer ◽

Gene Expression ◽

Cancer Patients ◽

Immune Gene ◽

Breast Cancer Patients ◽

Immune Gene Expression ◽

Healthy Women

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Differential Expression of MicroRNAs between Eutopic and Ectopic Endometrium in Ovarian Endometriosis

Journal of Biomedicine and Biotechnology ◽

10.1155/2010/369549 ◽

2010 ◽

Vol 2010 ◽

pp. 1-29 ◽

Cited By ~ 79

Author(s):

Nicoletta Filigheddu ◽

Ilaria Gregnanin ◽

Paolo E. Porporato ◽

Daniela Surico ◽

Beatrice Perego ◽

...

Keyword(s):

Gene Expression ◽

Differential Expression ◽

Posttranscriptional Regulation ◽

Noncoding Rna ◽

Critical Role ◽

Regulation Of Gene Expression ◽

Differentially Expressed ◽

Ovarian Endometriosis ◽

Eutopic Endometrium ◽

Ectopic Endometrium

Endometriosis, defined as the presence of endometrial tissue outside the uterus, is a common gynecological disease with poorly understood pathogenesis. MicroRNAs are members of a class of small noncoding RNA molecules that have a critical role in posttranscriptional regulation of gene expression by repression of target mRNAs translation. We assessed differentially expressed microRNAs in ectopic endometrium compared with eutopic endometrium in 3 patients through microarray analysis. We identified 50 microRNAs differentially expressed and the differential expression of five microRNAs was validated by real-time RT-PCR in other 13 patients. We identifiedin silicotheir predicted targets, several of which match the genes that have been identified to be differentially expressed in ectopicversuseutopic endometrium in studies of gene expression. A functional analysis of the predicted targets indicates that several of these are involved in molecular pathways implicated in endometriosis, thus strengthening the hypothesis of the role of microRNAs in this pathology.

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Prokineticin 1, homeobox A10, and progesterone receptor messenger ribonucleic acid expression in primary cultures of endometrial stromal cells isolated from endometrium of healthy women and from eutopic endometrium of women with endometriosis

Fertility and Sterility ◽

10.1016/j.fertnstert.2010.03.006 ◽

2010 ◽

Vol 94 (7) ◽

pp. 2558-2563 ◽

Cited By ~ 13

Author(s):

Federica Tiberi ◽

Anna Tropea ◽

Federica Romani ◽

Rosanna Apa ◽

Riccardo Marana ◽

...

Keyword(s):

Progesterone Receptor ◽

Stromal Cells ◽

Ribonucleic Acid ◽

Primary Cultures ◽

Endometrial Stromal Cells ◽

Eutopic Endometrium ◽

Messenger Ribonucleic Acid ◽

Healthy Women

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A Comparative Study of Gene Expression in Menstrual Blood-Derived Stromal Cells between Endometriosis and Healthy Women

BioMed Research International ◽

10.1155/2022/7053521 ◽

2022 ◽

Vol 2022 ◽

pp. 1-11

Author(s):

Seyedeh Saeideh Sahraei ◽

Faezeh Davoodi Asl ◽

Naser Kalhor ◽

Mohsen Sheykhhasan ◽

Hoda Fazaeli ◽

...

Keyword(s):

Gene Expression ◽

Stem Cells ◽

Gradient Centrifugation ◽

Angiogenic Factor ◽

Menstrual Blood ◽

Migration And Invasion ◽

Healthy Women ◽

Cell Cycle Related Gene ◽

New Biomarkers ◽

Age Range

Background. Research into the pathogenesis of endometriosis would substantially promote its effective treatment and early diagnosis. Currently, accumulating evidence has shed light on the importance of endometrial stem cells within the menstrual blood which are involved in the establishment and progression of endometriotic lesions in a retrograde manner. Objectives. We aimed to identify the differences in some genes’ expression between menstrual blood-derived mesenchymal stem cells (MenSCs) isolated from endometriosis patients (E-MenSCs) and MenSCs from healthy women (NE-MenSCs). Methods. Menstrual blood samples (2-3 mL) from healthy and endometriosis women in the age range of 22–35 years were collected. Isolated MenSCs by the Ficoll-Paque density-gradient centrifugation method were characterized by flow cytometry. MenSCs were evaluated for key related endometriosis genes by real-time-PCR. Results. E-MenSCs were morphologically different from NE-MenSCs and showed, respectively, higher and lower expression of CD10 and CD9. Furthermore, E-MenSCs had higher expression of Cyclin D1 (a cell cycle-related gene) and MMP-2 and MMP-9 (migration- and invasion-related genes) genes compared with NE-MenSCs. Despite higher cell proliferation in E-MenSCs, the BAX/BCL-2 ratio was significantly lower in E-MenSCs compared to NE-MenSCs. Also, the level of inflammatory genes such as IL1β, IL6, IL8, and NF-κB and stemness genes including SOX2 and SALL4 was increased in E-MenSCs compared with NE-MenSCs. Further, VEGF, as a potent angiogenic factor, showed a significant increase in E-MenSCs rather than NE-MenSCs. However, NE-MenSCs showed increased ER-α and β-catenin when compared with E-MenSCs. Conclusion. Here, we showed that there are gene expression differences between E-MenSCs and NE-MenSCs. These findings propose that MenSCs could play key role in the pathogenesis of endometriosis and further support the menstrual blood retrograde theory of endometriosis formation. This could be of great importance in exploiting promising therapeutic targets and new biomarkers for endometriosis treatment and prognosis.

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