RT Journal Article
SR Electronic
T1 Maternal circulating miRNAs that predict infant FASD outcomes influence placental maturation
JF Life Science Alliance
JO Life Sci. Alliance
FD Life Science Alliance LLC
SP e201800252
DO 10.26508/lsa.201800252
VO 2
IS 2
A1 Alexander M Tseng
A1 Amanda H Mahnke
A1 Alan B Wells
A1 Nihal A Salem
A1 Andrea M Allan
A1 Victoria HJ Roberts
A1 Natali Newman
A1 Nicole AR Walter
A1 Christopher D Kroenke
A1 Kathleen A Grant
A1 Lisa K Akison
A1 Karen M Moritz
A1 Christina D Chambers
A1 Rajesh C Miranda
A1 Collaborative Initiative on Fetal Alcohol Spectrum Disorders
YR 2019
UL https://www.life-science-alliance.org/content/2/2/e201800252.abstract
AB 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.