Butler Alexandra E, Cunningham Thomas Keith, Ramachandran Vimal, Diboun Ilhame, Halama Anna, Sathyapalan Thozhukat, Najafi-Shoushtari S Hani, Atkin Stephen L
Research Department, Royal College of Surgeons Ireland, Adliya, Bahrain.
Academic Diabetes, Endocrinology and Metabolism, Hull York Medical School, University of Hull, Hull, United Kingdom.
Front Reprod Health. 2021 Sep 23;3:719326. doi: 10.3389/frph.2021.719326. eCollection 2021.
Small non-coding RNAs, known as microRNAs (miRNAs), have emerging regulatory functions within the ovary that have been related to fertility. This study was undertaken to determine if circulating miRNAs reflect the changes associated with the parameters of embryo development and fertilization. In this cross-sectional pilot study. Plasma miRNAs were collected from 48 sequentially presenting women in the follicular phase prior to commencing fertilization (IVF). Circulating miRNAs were measured using locked nucleic acid (LNA)-based quantitative PCR (qPCR), while an updated miRNA data set was used to determine their level of expression. Body mass index and weight were associated with the miRNAs let7b-3p and miR-375, respectively ( < 0.05), with the same relationship being found between endometrium thickness at oocyte retrieval and miR-885-5p and miR-34a-5p ( < 0.05). In contrast, miR-1260a was found to be inversely associated with anti-Mullerian hormone (AMH; = 0.007), while miR-365a-3p, miR122-5p, and miR-34a-5p correlated with embryo fertilization rates ( < 0.05). However, when omitting cases of male infertility ( = 15), miR122-5p remained significant ( < 0.05), while miR-365a-3p and miR-34a-5p no longer differed; interestingly, however, miR1260a and mir93.3p became significant ( = 0.0087/0.02, respectively). Furthermore, age was negatively associated with miR-335-3p, miR-28-5p, miR-155-5p, miR-501-3p, and miR-497-5p ( < 0.05). Live birth rate was negatively associated with miR-335-3p, miR-100-5p, miR-497-5p, let-7d, and miR-574-3p ( < 0.05), but these were not significant when age was accounted for.However, with the exclusion of male factor infertility, all those miRNAs were no longer significant, though miR.150.5p emerged as significant ( = 0.042). A beta-regression model identified miR-1260a, miR-486-5p, and miR-132-3p ( < 0.03, = 0.0003, < 0.00001, respectively) as the most predictive for fertilization rate. Notably, changes in detectable miRNAs were not linked to cleavage rate, top quality embryos (G3D3), and blastocyst or antral follicle count. An ingenuity pathway analysis showed that miRNAs associated with age were also associated with the variables found in reproductive system diseases. Plasma miRNAs prior to the IVF cycle were associated with differing demographic and IVF parameters, including age, and may be predictive biomarkers of fertilization rate.
小非编码RNA，即微小RNA（miRNA），在卵巢内具有新出现的调控功能，这些功能与生育能力相关。本研究旨在确定循环miRNA是否反映与胚胎发育和受精参数相关的变化。在这项横断面试点研究中，在开始体外受精（IVF）之前，从48名处于卵泡期的连续就诊女性中收集血浆miRNA。使用基于锁核酸（LNA）的定量聚合酶链反应（qPCR）测量循环miRNA，同时使用更新的miRNA数据集来确定它们的表达水平。体重指数和体重分别与miRNA let7b - 3p和miR - 375相关（P<0.05），在取卵时的子宫内膜厚度与miR - 885 - 5p和miR - 34a - 5p之间也发现了相同的关系（P<0.05）。相比之下，发现miR - 1260a与抗苗勒管激素（AMH；P = 0.007）呈负相关，而miR - 365a - 3p、miR122 - 5p和miR - 34a - 5p与胚胎受精率相关（P<0.05）。然而，当排除男性不育病例（n = 15）时，miR122 - 5p仍然显著（P<0.05），而miR - 365a - 3p和miR - 34a - 5p不再有差异；然而，有趣的是，miR1260a和mir93.3p变得显著（分别为P = 0.0087/0.02）。此外，年龄与miR - 335 - 3p、miR - 28 - 5p、miR - 155 - 5p、miR - 501 - 3p和miR - 497 - 5p呈负相关（P<0.05）。活产率与miR - 335 - 3p、miR - 100 - 5p、miR - 497 - 5p、let - 7d和miR - 574 - 3p呈负相关（P<0.05），但在考虑年龄因素时这些并不显著。然而，排除男性因素不育后，所有这些miRNA不再显著，尽管miR.150.5p变得显著（P = 0.042）。一个β回归模型确定miR - 1260a、miR - 486 - 5p和miR - 132 - 3p（分别为P<0.03、P = 0.0003、P<0.00001）是受精率最具预测性的指标。值得注意的是，可检测到的miRNA变化与卵裂率、优质胚胎（G3D3）以及囊胚或窦卵泡计数无关。一项 Ingenuity 通路分析表明，与年龄相关的miRNA也与生殖系统疾病中发现的变量相关。IVF周期前的血浆miRNA与不同的人口统计学和IVF参数相关，包括年龄，并且可能是受精率的预测生物标志物。
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