Sundrani Deepali, Patil Sucheta, Kapare Aishwarya, Yadav Himanshi, Randhir Karuna, Kasibhatla Sunitha M, Gupte Sanjay, Joshi Sadhana
Mother and Child Health, ICMR- Collaborating Centre of Excellence (ICMR-CCoE), Bharati Vidyapeeth (Deemed to be University), Interactive Research School for Health Affairs (IRSHA), Pune, 411043, India.
C-DAC: Centre for Development of Advanced Computing, Pune, India.
J Assist Reprod Genet. 2025 Jul 14. doi: 10.1007/s10815-025-03583-6.
Assisted reproductive technology (ART) procedures are associated with placental dysfunction involving dysregulation of several molecular factors and pathways. MicroRNAs (miRNAs) are crucial epigenetic regulators involved in placental development and function. The objective was to identify differential miRNAs in the placentae of women conceived by ART procedures and explore their role by pathway analysis.
Fifty pregnant women who underwent ART procedure and 50 pregnant women with natural pregnancy (Non-ART group) were included in the study. Qiagen miRCURY LNA PCR Array was used to identify differential miRNAs from placental samples using qRT-PCR. Pathway enrichment analysis was performed for differentially expressed miRNAs using Enrichr integrated within ShinyGO v0.80.
Placental expression of 11 hsa-miRNAs (from 28 tested hsa-miRNAs) differed (5 upregulated and 6 downregulated) in the ART group. Pathway enrichment analysis revealed that upregulated miRNAs are associated with pathways such as vasculature development, and downregulated miRNAs were associated with xenobiotic stimulus, stress-activated MAPK cascade, circadian rhythm, insulin stimulus and secretion, cellular response to oxygen levels and fibroblast proliferation. Validation of miRNAs on larger sample size demonstrated that hsa-miR-30c-5p and hsa-miR-140a-5p were downregulated in the ART group. miRNA-mRNA target network analysis revealed that these miRNAs target 58 genes associated with regulation of VEGFA receptor signaling pathway, glomerulus vasculature development, long chain fatty-acyl-CoA biosynthesis, and apoptosis.
ART procedures are associated with altered placental miRNA expression, possibly contributing to disturbed placental angiogenesis. This study identified two essential miRNAs (hsa-miR-30c-5p and hsa-miR-140a-5p) associated with ART procedures that regulate placental and fetal growth and development.
辅助生殖技术（ART）操作与胎盘功能障碍相关，涉及多种分子因子和信号通路的失调。微小RNA（miRNA）是参与胎盘发育和功能的关键表观遗传调节因子。本研究旨在鉴定通过ART操作受孕女性胎盘组织中差异表达的miRNA，并通过通路分析探讨其作用机制。
本研究纳入50例行ART操作的孕妇和50例自然受孕孕妇（非ART组）。采用Qiagen miRCURY LNA PCR Array，通过qRT-PCR技术从胎盘样本中鉴定差异表达的miRNA。利用ShinyGO v0.80软件中的Enrichr工具对差异表达的miRNA进行通路富集分析。
在ART组中，28种检测的人源miRNA中有11种胎盘表达存在差异（5种上调，6种下调）。通路富集分析显示，上调的miRNA与血管发育等通路相关，而下调的miRNA与异生物刺激、应激激活的MAPK级联反应、昼夜节律、胰岛素刺激和分泌、细胞对氧水平的反应以及成纤维细胞增殖等通路相关。在更大样本量上对miRNA进行验证，结果显示ART组中hsa-miR-30c-5p和hsa-miR-140a-5p表达下调。miRNA-mRNA靶标网络分析表明，这些miRNA靶向58个与VEGFA受体信号通路调节、肾小球血管发育、长链脂肪酰辅酶A生物合成和细胞凋亡相关的基因。
ART操作与胎盘miRNA表达改变有关，可能导致胎盘血管生成紊乱。本研究鉴定出两种与ART操作相关的重要miRNA（hsa-miR-30c-5p和hsa-miR-140a-5p），它们调节胎盘和胎儿的生长发育。
