University of Louisville School of Medicine, Louisville, KY, 40202, USA.
Division of Reproductive Endocrinology and Infertility, NYU Winthrop Hospital, Mineola, NY, 11270, USA.
J Assist Reprod Genet. 2019 Jan;36(1):57-64. doi: 10.1007/s10815-018-1325-z. Epub 2018 Oct 1.
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.
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.
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.
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.
DNA 修复基因微小染色体维持复合物成分(MCM)8 和 9 与性腺发育、原发性卵巢功能不全(POI)和绝经年龄有关。我们的目的是描述月经周期中 MCM8 和 9 基因的表达,并比较 POI 与正常排卵女性的 MCM8/9 表达。
招募了正常排卵对照组(n=11)和不明原因 POI 受试者(n=6)。对照组在一个月经周期内提供了三个血液样本:(1)卵泡早期,(2)排卵,(3)黄体中期。11 名对照者中只有 6 名仅提供了卵泡期样本。闭经 POI 受试者提供了单次随机血样。使用 qRTPCR 评估外周血中 MCM8/9 的表达。采用 delta-Ct 测量进行分析;组间差异转化为倍数变化(FC)和置信区间(CI)。使用随机效应 ANOVA 比较月经周期各阶段的差异。使用两样本 t 检验比较两组之间的差异。
与卵泡期相比,MCM8 在排卵和黄体期的表达明显降低[黄体期与卵泡期的 FC 为 0.69(p=0.012,CI=0.53,0.90);排卵期与卵泡期的 FC 为 0.65(p=0.0057,CI=0.50,0.85)]。在整个月经周期中,MCM9 的表达没有变化。POI 与对照组之间的 MCM8/9 表达无显著差异。
本研究表明,与排卵和黄体期相比,MCM8 在月经周期的卵泡期表达更高。MCM9 没有出现周期性变化。POI 与对照组之间未检测到 MCM8/9 表达的显著差异;然而,我们建议进一步扩大样本量进行研究。