Trimester-specific associations between extracellular vesicle microRNAs and fetal growth

Abstract

Objective

Placenta-derived extracellular vesicles and their cargoes, especially microRNAs (EV-miRNAs), may contribute to fetal and placental development. During pregnancy, the levels of several maternal blood EV-miRNAs, including miRNAs of placental origin, vary among individuals and change throughout gestation. However, the effects of these miRNAs on fetal growth and trimester-specificity have not been fully elucidated. The purpose of this study is to test the hypothesis that the serum levels of two extracellular vesicles (EV)-miRNAs (miR-127-3p and miR-26b-5p), which may be involved in fetoplacental regulation, would be significantly associated with fetal growth in a trimester-specific manner.

Materials and methods

This is a single-center birth cohort of maternal serum samples obtained at both the second and third trimesters. To minimize the influence of confounding factors, the analysis was limited to singleton vaginal deliveries, resulting in 27 participants being included in this study. EV RNAs were isolated using a membrane affinity method, and the relative expression levels of miR-127-3p and miR-26b-5p were measured using the RT-qPCR method with miR-484 as control. The associations between the two EV-miRNAs and fetal and placental growth were evaluated using a linear regression model and compared between the two trimesters.

Results

EV-miR-127-3p levels tended to correlate inversely with the z-scores of birth weight for gestational age (BWGA) and placental weight for gestational age (PWGA) in the second trimester, but not in the third trimester. EV-miR-26b-5p levels were positively associated with birth weight in the second trimester, but this association was weakened in the third trimester.

Conclusion

Our results suggest a trimester-specific association of circulating miRNA levels with fetal and placental growth. The precise roles of EV-miR-127-3p and EV-miR-26b-5p in fetal and placental development warrant further investigation.

Keywords:

• Extracellular vesicles
• miRNAs
• pregnancy
• fetal and placental growth
• trimester-specificity

Acknowledgments

We would like to express our gratitude to the BC-GENIST participants and the members of Bioresource Research Center in Tokyo Medical and Dental University (TMDU), who provided the clinical materials from BioBank.

Disclosure statement

The authors declare no conflict of interest.

Data availability statement

The data that support the findings of this study are available from the corresponding author, NS, upon reasonable request.

Additional information

Funding

This research was partly supported by JSPS KAKENHI under Grant Numbers JP19K09821 and JP20K09594; Nanken-Kyoten, TMDU (2019–2020); and the Public Health Research Foundation.