Early diagnosis of placental abnormalities could potentially improve maternal-fetal health outcomes. Previous research has pointed to microRNAs (miRNAs) in particular as having potential for use in placental diagnostics. miRNAs regulate gene expression, and changes in miRNA levels throughout pregnancy may be involved in the development of diseases of the placenta, including preeclampsia and fetal growth restriction. A team of scientists funded by NICHD through the Human Placenta Project (HPP) has begun the work of characterizing miRNA signatures throughout gestation and across sexes—basic biology needed for the search for biomarkers of disease and future diagnostics.
Sex Differences in Maternal-Fetal Crosstalk
Sex differences in pregnancy outcomes have been well-documented for decades. For example, in the United States, male offspring are more likely than females to be born preterm. Researchers hypothesize that these differences occur early in pregnancy, but scientists have been unable to study this in detail during early placental development. In a small but important 2018 study, a team led by Margareta Pisarska, M.D., at Cedars-Sinai analyzed placental samples collected for routine genetic testing (chorionic villus sampling, or CVS) from male and female fetuses at the end of the first trimester.
The team used single-cell RNA sequencing to determine the impact of sex on what they call “maternal-fetal crosstalk,” the interactions that happen when fetal cells influence placental development. The researchers found differences in RNA signatures from male or female pregnancies, suggesting sex differences in gene expression that affect placental development. This information will be important as researchers search for biomarkers of pregnancy-related disease.
Gestational Differences in miRNA Signatures
In a more recent and larger study, the team used CVS samples taken late in the first trimester and compared them with samples taken at birth. They determined the miRNA profile for healthy pregnancies, getting a baseline of miRNA expression across gestation. These baseline profiles serve as miRNA signatures that lay the groundwork for using miRNAs to monitor maternal-fetal health throughout pregnancy.
Learn more about the team
Principal Investigator(s):
Learn more about the HPP-funded project:
Noncoding RNA regulation of the human placental transcriptome among the sexes
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