TY - JOUR
T1 - Placental dysfunction is associated with altered microRNA expression in pregnant women with low folate status
AU - Baker, Bernadette
AU - Mackie, Fiona
AU - Lean, Samantha
AU - Greenwood, Susan
AU - Heazell, Alexander
AU - Forbes, Karen
AU - Jones, Rebecca
AU - MacKie, Fiona
PY - 2017/8
Y1 - 2017/8
N2 - Scope
Low maternal folate status during pregnancy increases the risk of delivering small for gestational age (SGA) infants, but the mechanistic link between maternal folate status, SGA, and placental dysfunction is unknown. microRNAs (miRNAs) are altered in pregnancy pathologies and by folate in other systems. We hypothesized that low maternal folate status causes placental dysfunction, mediated by altered miRNA expression.
Methods and results
A prospective observational study recruited pregnant adolescents and assessed third trimester folate status and placental function. miRNA array, QPCR, and bioinformatics identified placental miRNAs and target genes. Low maternal folate status is associated with higher incidence of SGA infants (28% versus 13%, p < 0.05) and placental dysfunction, including elevated trophoblast proliferation and apoptosis (p < 0.001), reduced amino acid transport (p < 0.01), and altered placental hormones (pregnancy-associated plasma protein A, progesterone, and human placental lactogen). miR-222-3p, miR-141-3p, and miR-34b-5p were upregulated by low folate status (p < 0.05). Bioinformatics predicted a gene network regulating cell turnover. Quantitative PCR demonstrated that key genes in this network (zinc finger E-box binding homeobox 2, v-myc myelocytomatosis viral oncogene homolog (avian), and cyclin-dependent kinase 6) were reduced (p < 0.05) in placentas with low maternal folate status.
Conclusion
This study supports that placental dysfunction contributes to impaired fetal growth in women with low folate status and suggests altered placental expression of folate-sensitive miRNAs and target genes as a mechanistic link.
AB - Scope
Low maternal folate status during pregnancy increases the risk of delivering small for gestational age (SGA) infants, but the mechanistic link between maternal folate status, SGA, and placental dysfunction is unknown. microRNAs (miRNAs) are altered in pregnancy pathologies and by folate in other systems. We hypothesized that low maternal folate status causes placental dysfunction, mediated by altered miRNA expression.
Methods and results
A prospective observational study recruited pregnant adolescents and assessed third trimester folate status and placental function. miRNA array, QPCR, and bioinformatics identified placental miRNAs and target genes. Low maternal folate status is associated with higher incidence of SGA infants (28% versus 13%, p < 0.05) and placental dysfunction, including elevated trophoblast proliferation and apoptosis (p < 0.001), reduced amino acid transport (p < 0.01), and altered placental hormones (pregnancy-associated plasma protein A, progesterone, and human placental lactogen). miR-222-3p, miR-141-3p, and miR-34b-5p were upregulated by low folate status (p < 0.05). Bioinformatics predicted a gene network regulating cell turnover. Quantitative PCR demonstrated that key genes in this network (zinc finger E-box binding homeobox 2, v-myc myelocytomatosis viral oncogene homolog (avian), and cyclin-dependent kinase 6) were reduced (p < 0.05) in placentas with low maternal folate status.
Conclusion
This study supports that placental dysfunction contributes to impaired fetal growth in women with low folate status and suggests altered placental expression of folate-sensitive miRNAs and target genes as a mechanistic link.
KW - fetal growth
KW - folate deficiency
KW - gene expression
KW - microRNA
KW - placental dysfunction
U2 - 10.1002/mnfr.201600646
DO - 10.1002/mnfr.201600646
M3 - Article
SN - 1613-4125
VL - 61
JO - Molecular Nutrition & Food Research
JF - Molecular Nutrition & Food Research
IS - 8
M1 - 1600646
ER -