Lahore Institute of Fertility and Endocrinology, Hameed Latif Hospital, 14 Abu-Bakar Block New Garden Town, 54800, Lahore, Pakistan.
Department of Human Genetics and Molecular biology, University of Health Sciences, Lahore, 54600, Pakistan.
Reprod Biol Endocrinol. 2021 May 15;19(1):72. doi: 10.1186/s12958-021-00754-9.
MicroRNAs (miRNAs) are small RNA molecules that modulate post-transcriptional gene regulation. They are often used as promising non-invasive biomarkers for the early diagnosis of cancer. However, their roles in assisted reproduction are still unknown.
This prospective study was designed to evaluate the expression profiles of seven extracellular miRNAs (miR-7-5p, miR-202-5p, miR-378-3p, miR-224, miR-320a, miR-212-3p, and miR-21-5p) in human follicular fluid (FF) to explore the outcomes of in vitro fertilization (IVF). Of 255 women, 145 were without polycystic ovary syndrome (PCOS), and their ovarian assets were normal (NOR), while 110 were with normo-androgenic PCOS.
The combination of six FF miRNAs expression profile discriminated between PCOS and NOR women with a sensitivity of 79.2% and a specificity of 87.32% (AUC = 0.881 [0.61; 0.92], p = 0.001). MiR-202-5p significantly had a lower abundance level, and miR-378-3p had a high abundance level in pooled FF samples from patients treated with human menopausal gonadotropin (hMG) than those treated with recombinant follicle-stimulating hormone (rFSH) (p < 0.001). Our results showed that miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 in NOR patients with a sensitivity of 80% and specificity of 71%, (AUC = [0.753 (0.651; 0.855)], p = 0.001). For clinical pregnancy outcome prediction, FF miRNA-21 exhibited high sensitivity (74.8%) and specificity (83.7%) with the AUC value of 0.774 (0.682; 0.865).
Conclusively, our results provide evidence that miR-7-5p, miR-378-3p, miR-224, miR-212-3p were a differentially high expression in normo-androgenic PCOS patients than NOR patients. While miRNA-320a was significantly different in top-quality embryos versus non-top-quality embryos on day 3 (p = 0.001). The expression level of FF miR-212-3p was significantly related to the probability of embryos to develop into a high-quality blastocyst in patients with normal ovarian reserve.
微小 RNA（miRNAs）是一种调节转录后基因调控的小 RNA 分子。它们常被用作癌症早期诊断有前途的非侵入性生物标志物。然而，它们在辅助生殖中的作用尚不清楚。
本前瞻性研究旨在评估 255 名女性中 7 种细胞外泌体 miRNA（miR-7-5p、miR-202-5p、miR-378-3p、miR-224、miR-320a、miR-212-3p 和 miR-21-5p）在人卵泡液（FF）中的表达谱，以探讨体外受精（IVF）的结果。其中 145 名无多囊卵巢综合征（PCOS）患者的卵巢功能正常（NOR），110 名患有正常雄激素的 PCOS 患者。
6 种 FF miRNA 表达谱的组合可区分 PCOS 和 NOR 妇女，其敏感性为 79.2%，特异性为 87.32%（AUC=0.881[0.61；0.92]，p=0.001）。miR-202-5p 的丰度水平显著降低，而 miR-378-3p 在接受人绝经期促性腺激素（hMG）治疗的患者的 pooled FF 样本中的丰度水平高于接受重组卵泡刺激素（rFSH）治疗的患者（p<0.001）。我们的结果表明，在 NOR 患者中，miRNA-320a 在第 3 天的优质胚胎与非优质胚胎之间存在显著差异，其敏感性为 80%，特异性为 71%（AUC=[0.753（0.651；0.855]），p=0.001）。对于临床妊娠结局预测，FF miRNA-21 表现出较高的敏感性（74.8%）和特异性（83.7%），AUC 值为 0.774（0.682；0.865）。
总之，我们的研究结果表明，miR-7-5p、miR-378-3p、miR-224、miR-212-3p 在正常雄激素的 PCOS 患者中表达水平高于 NOR 患者。而 miRNA-320a 在第 3 天的优质胚胎与非优质胚胎之间存在显著差异（p=0.001）。FF miR-212-3p 的表达水平与具有正常卵巢储备功能的患者胚胎发育成高质量囊胚的概率显著相关。
