Sexually dimorphic patterns in maternal circulating microRNAs in pregnancies complicated by fetal growth restriction

From Springer Nature via Jisc Publications Router ; History: received 2021-08-18, accepted 2021-10-27, registration 2021-11-01, pub-electronic 2021-11-17, online 2021-11-17, collection 2021-12 ; Publication status: Published ; Funder: tommy's baby charity; doi: http://dx.doi.org/10.13039/501100000306 ; Funder: medical research foundation; doi: http://dx.doi.org/10.13039/501100009187; Grant(s): MR/R023166/1 ; Abstract: Background: Current methods fail to accurately predict women at greatest risk of developing fetal growth restriction (FGR) or related adverse outcomes, including stillbirth. Sexual dimorphism in these adverse pregnancy outcomes is well documented as are sex-specific differences in gene and protein expression in the placenta. Circulating maternal serum microRNAs (miRNAs) offer potential as biomarkers that may also be informative of underlying pathology. We hypothesised that FGR would be associated with an altered miRNA profile and would differ depending on fetal sex. Methods: miRNA expression profiles were assessed in maternal serum (> 36 weeks’ gestation) from women delivering a severely FGR infant (defined as an individualised birthweight centile (IBC) < 3rd) and matched control participants (AGA; IBC = 20–80th), using miRNA arrays. qPCR was performed using specific miRNA primers in an expanded cohort of patients with IBC < 5th (n = 15 males, n = 16 females/group). Maternal serum human placental lactogen (hPL) was used as a proxy to determine if serum miRNAs were related to placental dysfunction. In silico analyses were performed to predict the potential functions of altered miRNAs. Results: Initial analyses revealed 11 miRNAs were altered in maternal serum from FGR pregnancies. In silico analyses revealed all 11 altered miRNAs were located in a network of genes that regulate placental function. Subsequent analysis demonstrated four miRNAs showed sexually dimorphic patterns. miR-28-5p was reduced in FGR pregnancies (p < 0.01) only when there was a female offspring and miR-301a-3p was ...