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Maternal Extracellular Vesicles During Pregnancy and Autism Risk in Children
Delia McGowan1, Serena Nencini2, William Yakah2
1Barnard College, Columbia University, New York, NY, United States.
Insights
Maternal prenatal extracellular vesicles (EVs) RNA cargo, not concentration or size, is linked to autism likelihood in children. Further research is needed to confirm these preliminary findings.
Area of Science:
- Perinatal research
- Neurodevelopmental disorders
- Biomarker discovery
Background:
- Extracellular vesicles (EVs) are implicated in intercellular signaling and show differences in autism.
- The role of maternal EVs during pregnancy in offspring autism risk is largely unknown.
- This study investigates the association between prenatal maternal EV concentration and cargo with childhood autism likelihood.
Purpose of the Study:
- To evaluate the association of maternal prenatal plasma extracellular vesicle (EV) concentration and RNA cargo with childhood autism likelihood.
- To identify specific RNA molecules within maternal EVs that may serve as biomarkers for autism risk.
- To explore the biological pathways associated with differentially expressed RNAs in maternal EVs.
Main Methods:
- Maternal plasma collected during pregnancy (15-23 weeks) was used to isolate extracellular vesicles (EVs).
- EVs were analyzed for concentration, size, CD63 levels, and small RNA sequencing.
- Children's autism risk was assessed at 4.5-6 years using the Social Communication Questionnaire; RNA cargo differences were analyzed between high-risk and low-risk groups.
Main Results:
- No significant differences were found in EV concentration, mean size, or CD63 levels between groups.
- One hundred forty-five RNAs were differentially contained in maternal EVs, with most downregulated in the high-risk autism group.
- Differentially expressed RNAs were associated with immune signaling, intracellular trafficking, protein turnover, and neurodevelopment pathways, with some overlapping SFARI Gene database genes.
Conclusions:
- Preliminary evidence suggests maternal prenatal EV RNA cargo is associated with childhood autism likelihood.
- Specific RNA profiles within maternal EVs may indicate a child's risk for autism.
- Larger studies are required to validate these findings and explore the role of prenatal EVs in autism pathogenesis.
Background:
Differences in extracellular vesicles (EVs), bioactive nanoparticles involved in intercellular signaling, have been reported in those with autism. However, little is known about the association between maternal EVs during pregnancy and the likelihood of autism in offspring. This study evaluated the association of the concentration and cargo material of EVs in prenatal maternal plasma with childhood autism likelihood.
Methods:
Participants in the Nulliparous Pregnancy Outcomes Study provided maternal plasma at 15-23 weeks' gestational age. EVs were isolated by ultracentrifugation, and concentration, mean size, CD63 levels, and RNA cargo were assessed by nanoparticle tracking analysis, ELISA, and small RNA sequencing. At 4.5-6 years of age, parents completed the Social Communication Questionnaire. Thirty-one children at high-risk for autism were matched to 31 low-risk children on sex, age, and gestational age. Differential RNA transcript analysis and over representation analysis were performed.
Results:
There were no group differences in CD63 levels, mean particle size, or EV concentration (p>0.1). Nominal bin-level differences were observed at 280-290 nm and 430-440 nm before multiple-comparison correction. One hundred forty-five RNAs, including protein-coding RNAs, piRNAs, lncRNAs, miRNAs, snoRNAs, snRNAs, and tRNAs, were differentially contained, most of them downregulated in those at high risk of autism. These RNAs mapped to pathways involved in immune/inflammatory signaling, intracellular trafficking, protein turnover, and neurodevelopment. Six of the 62 (9.7%) differentially contained protein-coding RNAs overlapped with genes in the SFARI Gene database.
Limitations:
Large studies involving individuals diagnosed with autism are needed to evaluate the role of prenatal EVs in the pathogenesis of the condition. Additionally, prenatal sampling of EVs across multiple timepoints and subsequent deconvolution to determine the source of the EVs will strengthen interpretability and veracity of our findings.
Conclusions:
These findings provide preliminary evidence that maternal prenatal EV RNA cargo is associated with childhood autism likelihood.
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