Dataset Information

Minichromosome maintenance complex component 8 and 9 gene expression in the menstrual cycle and unexplained primary ovarian insufficiency.

ABSTRACT: PURPOSE:DNA repair genes Minichromosome maintenance complex component (MCM) 8 and 9 have been linked with gonadal development, primary ovarian insufficiency (POI), and age at menopause. Our objective was to characterize MCM 8 and 9 gene expression in the menstrual cycle, and to compare MCM 8/9 expression in POI vs normo-ovulatory women. METHODS:Normo-ovulatory controls (n?=?11) and unexplained POI subjects (n?=?6) were recruited. Controls provided three blood samples within one menstrual cycle: (1) early follicular phase, (2) ovulation, and (3) mid-luteal phase. Six of 11 controls only provided a follicular phase sample. Amenorrheic POI subjects provided a single, random blood sample. MCM8/9 expression in peripheral blood was assessed with qRTPCR. Analyses were performed using delta-Ct measurements; group differences were transformed to a fold change (FC) and confidence interval (CI). Differences across menstrual cycle phases were compared using random effects ANOVA. Two-sample t tests were used to compare two groups. RESULTS:MCM8 expression was significantly lower at ovulation and during the luteal phase, when compared to the follicular phase [FC?=?0.69 in the luteal vs follicular phase (p?=?0.012, CI?=?0.53, 0.90); and 0.65 in the ovulatory vs follicular phase (p?=?0.0057, CI?=?0.50, 0.85)]. No change in MCM9 expression was noted throughout the menstrual cycle. No significant difference was seen in MCM8/9 expression when comparing POI to control subjects. CONCLUSIONS:Our study showed greater MCM8 expression in the follicular phase of the menstrual cycle, compared to the ovulatory and luteal phases. No cyclic changes were seen with MCM9. Significant differences in MCM8/9 expression were not detected between POI and controls; however, we recommend further investigation with a larger sample population.

SUBMITTER: Dondik Y

PROVIDER: S-EPMC6338603 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature

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Minichromosome maintenance complex component 8 and 9 gene expression in the menstrual cycle and unexplained primary ovarian insufficiency.

Dondik Yelena Y Lei Zhenmin Z Gaskins Jeremy J Pagidas Kelly K

Journal of assisted reproduction and genetics 20181001 1

<h4>Purpose</h4>DNA repair genes Minichromosome maintenance complex component (MCM) 8 and 9 have been linked with gonadal development, primary ovarian insufficiency (POI), and age at menopause. Our objective was to characterize MCM 8 and 9 gene expression in the menstrual cycle, and to compare MCM 8/9 expression in POI vs normo-ovulatory women.<h4>Methods</h4>Normo-ovulatory controls (n = 11) and unexplained POI subjects (n = 6) were recruited. Controls provided three blood samples within one me ...[more]

PMID: 30276597

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Project description:Esophageal squamous cell carcinoma (ESCC), the main subtype of esophageal cancer (EC), is a common lethal type of cancer with a high mortality rate. The aim of the present study was to select key relevant genes and identify potential mechanisms involved in the development of ESCC based on bioinformatics analysis. Minichromosome maintenance 6 complex component (MCM6) has been identified to be upregulated in multiple malignancies; however, its contributions to ESCC remain unclear. For the purposes of the present study, four datasets were downloaded from the Gene Expression Omnibus (GSE63941, GSE26886, GSE17351 and GSE77861), and the intersection of the differentially expressed genes was obtained using a Venn diagram. The protein‑protein interaction was then constructed, and the modules were verified by Cytoscape, in which the key genes have a high connectivity degree with other genes. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway were subsequently filtered out to analyze the development of ESCC. MCM6, an upregulated gene, was selected and connected with most of the other genes, for further research validation. The expression levels of MCM6 were then assessed using the Oncomine, GEPIA and UALCAN databases and validated in both ESCC tissues samples and cell lines by immunohistochemistry and RT‑qPCR. Cell counting kit‑8 (CCK‑8), flow cytometry, wound healing and Transwell assays were used to determine the proliferation, apoptosis, cell cycle, migration and invasion of ESCC cells. A total of 24 genes were identified by a series of bioinformatics analyses and the results revealed that the genes were associated with DNA replication and cell cycle. Experimental validation revealed that MCM6 expression was significantly elevated in both ESCC tissues and cell lines. The results were consistent with those of bioinformatics analysis. Furthermore, the knockdown of MCM6 inhibited cell proliferation, migration and invasion and promoted cell apoptosis, and made cells arrested in S stage. In summary, the findings of bioinformatics analysis provided a novel hypothesis for ESCC progression. In particular, the aberrantly elevated expression of MCM6 is a potential biomarker for ESCC diagnosis and treatment.

Project description:Occult primary ovarian insufficiency (also known as incipient ovarian failure or diminished ovarian reserve) is defined as serum AMH level ?1.1ng/mL in women under age 30. Limited data is available regarding the prevalence of occult POI, the preceding menstrual characteristics and its natural course in otherwise healthy young females. We aimed in this prospective observational study to determine the prevalence of occult POI in young females (< age 30) screened with serum AMH measurement; and analyze the patterns of change in their menstruation at initial assessment and one-year follow-up in relation to the changes in ovarian reserve quantitatively assessed with AMH and AFC. 963 young female college students under age 30 voluntarily participated in this study. 43 of them (4.4%) were diagnosed with occult POI as their AMH levels were ? 1.1ng/mL. Thirty-eight (83.4%) of them have regular cycles and denied any menstrual irregularity in the last 12 months. This rate was not statistically different from 7.3% of those with AMH>1.1ng/mL who reported at least one abnormal menstrual cycle in the last year (p = 0.36). Cycle length was significantly shorter in females with AMH ? 1.1ng/mL compared to those with AMH>1.1ng/mL (25.1±3.2 vs. 31.2±2.8 respectively, p<0.001). Karyotype, FMR-1 mutation analyses and auto-antibody screening returned normal in all. At one-year follow-up AMH, AFC and mean cycle length were further reduced compared to their values at initial assessment. Now, a greater proportion of the participants with occult POI were menstruating regularly at every 21 days compared to the initial evaluation one year ago (39.5% vs. 13.9% respectively, p = 0.013). Twenty-five underwent oocyte cryopreservation. These findings underscore the importance of screening young females with AMH for possible occult POI. It also emphasizes that young females with critically diminished ovarian reserve may continue to menstruate regularly without any characteristic menstrual abnormality other than shortening of cycle length.

Dataset Information

Minichromosome maintenance complex component 8 and 9 gene expression in the menstrual cycle and unexplained primary ovarian insufficiency.

Publications

Minichromosome maintenance complex component 8 and 9 gene expression in the menstrual cycle and unexplained primary ovarian insufficiency.

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