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

Abstract Background During 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...

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Main Authors: Yangwu Fang, Chan Wan, Youlu Wen, Ze Wu, Jing Pan, Mei Zhong, Nanbert Zhong
Format: Article
Language:English
Published: BMC 2021-04-01
Series:Journal of Translational Medicine
Subjects:
Online Access:https://doi.org/10.1186/s12967-021-02821-6
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author Yangwu Fang
Chan Wan
Youlu Wen
Ze Wu
Jing Pan
Mei Zhong
Nanbert Zhong
author_facet Yangwu Fang
Chan Wan
Youlu Wen
Ze Wu
Jing Pan
Mei Zhong
Nanbert Zhong
author_sort Yangwu Fang
collection DOAJ
description Abstract Background During 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. Methods Blood 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. Results SVAT-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 of STX8, SLC18A2, and SYP with sPTB; SVAT-lncRNA and SVAT-mRNA of STX8 with PE; and SVAT-lncRNA and SVAT-mRNA of SV2C as well as SVAT-mRNA of SYP with GDM. Conclusion Variant 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.
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spelling doaj.art-670673f73be24cc3b3cbfb02ca281efa2022-12-21T16:53:59ZengBMCJournal of Translational Medicine1479-58762021-04-0119111110.1186/s12967-021-02821-6Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnanciesYangwu Fang0Chan Wan1Youlu Wen2Ze Wu3Jing Pan4Mei Zhong5Nanbert Zhong6Department of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical UniversitySino-US Center of Translational Medicine for Development Disabilities, Southern Medical UniversityDepartment of Psychiatry, Guangdong 999 Brain HospitalSino-US Center of Translational Medicine for Development Disabilities, Southern Medical UniversitySino-US Center of Translational Medicine for Development Disabilities, Southern Medical UniversityDepartment of Obstetrics and Gynecology, Nanfang Hospital, Southern Medical UniversitySino-US Center of Translational Medicine for Development Disabilities, Southern Medical UniversityAbstract Background During 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. Methods Blood 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. Results SVAT-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 of STX8, SLC18A2, and SYP with sPTB; SVAT-lncRNA and SVAT-mRNA of STX8 with PE; and SVAT-lncRNA and SVAT-mRNA of SV2C as well as SVAT-mRNA of SYP with GDM. Conclusion Variant 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.https://doi.org/10.1186/s12967-021-02821-6SynapseSpontaneous preterm birthPreeclampsiaGestational diabetes mellitusExosomes
spellingShingle Yangwu Fang
Chan Wan
Youlu Wen
Ze Wu
Jing Pan
Mei Zhong
Nanbert Zhong
Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies
Journal of Translational Medicine
Synapse
Spontaneous preterm birth
Preeclampsia
Gestational diabetes mellitus
Exosomes
title Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies
title_full Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies
title_fullStr Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies
title_full_unstemmed Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies
title_short Autism-associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies
title_sort autism associated synaptic vesicle transcripts are differentially expressed in maternal plasma exosomes of physiopathologic pregnancies
topic Synapse
Spontaneous preterm birth
Preeclampsia
Gestational diabetes mellitus
Exosomes
url https://doi.org/10.1186/s12967-021-02821-6
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