Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturation

Life Sci Alliance. 2019 Mar 4;2(2):e201800252. doi: 10.26508/lsa.201800252. Print 2019 Apr.


Prenatal alcohol exposure (PAE), like other pregnancy complications, can result in placental insufficiency and fetal growth restriction, although the linking causal mechanisms are unclear. We previously identified 11 gestationally elevated maternal circulating miRNAs (HEamiRNAs) that predicted infant growth deficits following PAE. Here, we investigated whether these HEamiRNAs contribute to the pathology of PAE, by inhibiting trophoblast epithelial-mesenchymal transition (EMT), a pathway critical for placental development. We now report for the first time that PAE inhibits expression of placental pro-EMT pathway members in both rodents and primates, and that HEamiRNAs collectively, but not individually, mediate placental EMT inhibition. HEamiRNAs collectively, but not individually, also inhibited cell proliferation and the EMT pathway in cultured trophoblasts, while inducing cell stress, and following trophoblast syncytialization, aberrant endocrine maturation. Moreover, a single intravascular administration of the pooled murine-expressed HEamiRNAs, to pregnant mice, decreased placental and fetal growth and inhibited the expression of pro-EMT transcripts in the placenta. Our data suggest that HEamiRNAs collectively interfere with placental development, contributing to the pathology of PAE, and perhaps also, to other causes of fetal growth restriction.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Alcoholism / complications
  • Animals
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Circulating MicroRNA / metabolism*
  • Epithelial-Mesenchymal Transition / drug effects
  • Ethanol / administration & dosage
  • Ethanol / adverse effects*
  • Female
  • Fetal Alcohol Spectrum Disorders / etiology
  • Fetal Alcohol Spectrum Disorders / metabolism*
  • Fetal Growth Retardation / etiology
  • Fetal Growth Retardation / metabolism
  • Humans
  • Macaca mulatta
  • Mice
  • Mice, Inbred C57BL
  • Placentation / drug effects*
  • Pregnancy
  • Prenatal Exposure Delayed Effects / metabolism*
  • Rats
  • Rats, Sprague-Dawley
  • Trophoblasts / metabolism


  • Circulating MicroRNA
  • Ethanol