miRNA-210-3p regulates trophoblast proliferation and invasiveness through fibroblast growth factor 1 in selective intrauterine growth restriction

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 1 alpha (HIF1 alpha) 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, HIF1 alpha 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.