Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies

Abstract

AbstractBackgroundDuring intrauterine development, the formation and function of synaptic vesicles (SVs) are thought to be fundamental conditions essential for normal development of the brain. Lacking advanced technology during the intrauterine period, such as longitudinal real-time monitoring of the SV-associated transcripts (SVATs), which include six pairs of lncRNA-mRNA, has limited acquisition of the dynamic gene expression profile (GEP) of SVATs. We previously reported the differential expression of SVATs in the peripheral blood of autistic children. The current study was designed to determine the dynamic profiles of differentially-expressed SVATs in circulating exosomes (EXs) derived from autistic children and pregnant women at different gestational ages.MethodsBlood samples were collected from autistic children and women with variant physiopathologic pregnancies. EXs were isolated with an ExoQuick Exosome Precipitation Kit and characterized by transmission electron microscopy (TEM), nanoparticle tracking analysis (NTA), and Western blotting. The expression of lncRNAs and lncRNA-targeted mRNAs were quantified using real-time PCR.ResultsSVAT-associated lncRNAs-mRNAs were detected in autistic children and differentially expressed from the first trimester of pregnancy to the term of delivery. Pathologic pregnancies, including spontaneous preterm birth (sPTB), preeclampsia (PE), and gestational diabetes mellitus (GDM), were compared to normal physiologic pregnancies, and shown to exhibit specific correlations between SVAT-lncRNA and SVAT-mRNA ofSTX8,SLC18A2, andSYPwith sPTB; SVAT-lncRNA and SVAT-mRNA ofSTX8with PE; and SVAT-lncRNA and SVAT-mRNA ofSV2Cas well as SVAT-mRNA ofSYPwith GDM.ConclusionVariant complications in pathologic pregnancies may alter the GEP of SVATs, which is likely to affect the intrauterine development of neural circuits and consequently influence fetal brain development.