Placental expression of miR-517-5p and miR-518f-5p: Fetal sex-specific relations with human fetoplacental growth

Objective: We aimed to assess association of chromosome 19 miRNA cluster microRNAs (miR-517-5p and miR-518f-5p) expression with maternal, placental and newborn parameters and with their potential angiogenesis-associated target genes ENG, VEGF and FLT in a set of 68 small- (SGA, n = 30) and appropriate- (AGA, n = 38) for gestational age full-term singleton pregnancies, in relation to fetal sex.

Study design: In this retrospective case-control study, placental transcript abundances of miR-517-5p and miR-518f-5p were assessed by real-time quantitative PCR after normalization to reference miRNA, mir-16-5p. Placental transcript abundances of VEGF, FLT and ENG were assessed after normalizing to a set of reference genes.

Results: Placental miR-517-5p transcript abundance was negatively associated with birth weight [β = -88.778, P = 0.006, 95% confidence interval (CI): -151.645, -25.911] and placental weight (β = -14.683, P = 0.007, 95% CI: -25.254, -4.112) and this association with birth weight was specific to the AGA births (β = -59.207, P = 0.037, 95% CI: -114.522, -3.891). miR-518f-5p transcript abundance was negatively associated with placental weight (β = -6.250, P = 0.034, 95% CI: -11.940, -0.559) specifically in the AGA male births (n = 16). Placental VEGF transcript abundance was negatively associated with that of miR-517-5p specifically in SGA female births (n = 14; Spearman's ρ = -0.705, P = 0.005) and with miR-518f-5p transcript abundance specifically in SGA births (Spearman's ρ = -0.437, P = 0.016) and in SGA male births (n = 16; Spearman's ρ = -0.516, P = 0.041).

Conclusion: We conclude that placental miR-517-5p could be playing a key role in the pathophysiology of fetal growth restriction, which can be potentially targeted through maternal lifestyle modifications for improving fetoplacental growth.