Department of Obstetrics and Gynecology, Fetal Medicine Center, The First Affiliated Hospital of Sun Yat-sen University, Guangzhou, Guangdong, China.
Key Laboratory of Gene Engineering of the Ministry of Education and State Key Laboratory of Biocontrol, School of Life Sciences, Sun Yat-sen University, Guangzhou, Guangdong, China.
J Cell Mol Med. 2019 Jun;23(6):4422-4433. doi: 10.1111/jcmm.14335. Epub 2019 Apr 16.
Selective intrauterine growth restriction (sIUGR), which affects approximately 10%-15% of monochorionic (MC) twin pregnancies, is highly associated with intrauterine foetal death and neurological impairment in both twins. Data suggest that unequal sharing of the single placenta is the main contributor to birth weight discordance. While MC twins and their placenta derive from a single zygote and harbour almost identical genetic material, the underlying mechanisms of phenotypic discrepancies in MC twins remain unclear. MicroRNAs are small non-coding RNA molecules that regulate gene expression but do not change the DNA sequence. Our preliminary study showed that microRNA-210-3p (miR-210-3p) was significantly upregulated in the placental share of the smaller sIUGR twin. Here, we investigate the potential role of miR-210-3p in placental dysplasia, which generally results from dysfunction of trophoblast cells. Functional analysis revealed that miR-210-3p, induced by hypoxia-inducible factor 1α (HIF1α) under hypoxic conditions, suppressed the proliferation and invasiveness of trophoblast cell lines. Further RNA sequencing analysis and luciferase reporter assays were performed, revealing that fibroblast growth factor 1 (FGF1) is an influential target gene of miR-210-3p. Moreover, correlations among miR-210-3p levels, HIF1α and FGF1 expression and the smaller placental share were validated in sIUGR specimens. These findings suggest that upregulation of miR-210-3p may contribute to impaired placentation of the smaller twin by decreasing FGF1 expression in sIUGR.
选择性宫内生长受限(sIUGR)影响约 10%-15%的单绒毛膜(MC)双胎妊娠,与宫内胎儿死亡和双胎的神经损伤高度相关。数据表明,单一胎盘的不均等分配是导致出生体重不一致的主要原因。虽然 MC 双胞胎及其胎盘来自单个受精卵,并具有几乎相同的遗传物质,但 MC 双胞胎表型差异的潜在机制尚不清楚。microRNA 是一种小的非编码 RNA 分子,可调节基因表达,但不改变 DNA 序列。我们的初步研究表明,microRNA-210-3p(miR-210-3p)在较小的 sIUGR 双胞胎的胎盘份额中显著上调。在这里,我们研究了 miR-210-3p 在胎盘发育不良中的潜在作用,胎盘发育不良通常是由于滋养细胞功能障碍引起的。功能分析显示,缺氧诱导因子 1α(HIF1α)在缺氧条件下诱导的 miR-210-3p 抑制了滋养细胞系的增殖和侵袭能力。进一步的 RNA 测序分析和荧光素酶报告基因检测表明,成纤维细胞生长因子 1(FGF1)是 miR-210-3p 的一个有影响的靶基因。此外,在 sIUGR 标本中验证了 miR-210-3p 水平、HIF1α 和 FGF1 表达与较小胎盘份额之间的相关性。这些发现表明,miR-210-3p 的上调可能通过降低 sIUGR 中 FGF1 的表达,导致较小双胞胎的胎盘形成受损。