microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine Model
Autism Spectrum Disorder (ASD) has been associated with a complex interplay between genetic and environmental factors. Prenatal stress exposure has been identified as a possible risk factor, although most stress-exposed pregnancies do not result in ASD. The serotonin transporter (SERT) gene has been...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-09-01
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| Series: | Journal of Personalized Medicine |
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| Online Access: | https://www.mdpi.com/2075-4426/13/9/1412 |
| _version_ | 1797579233085620224 |
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| author | Taeseon Woo Candice King Nick I. Ahmed Madison Cordes Saatvika Nistala Matthew J. Will Clark Bloomer Nataliya Kibiryeva Rocio M. Rivera Zohreh Talebizadeh David Q. Beversdorf |
| author_facet | Taeseon Woo Candice King Nick I. Ahmed Madison Cordes Saatvika Nistala Matthew J. Will Clark Bloomer Nataliya Kibiryeva Rocio M. Rivera Zohreh Talebizadeh David Q. Beversdorf |
| author_sort | Taeseon Woo |
| collection | DOAJ |
| description | Autism Spectrum Disorder (ASD) has been associated with a complex interplay between genetic and environmental factors. Prenatal stress exposure has been identified as a possible risk factor, although most stress-exposed pregnancies do not result in ASD. The serotonin transporter (SERT) gene has been linked to stress reactivity, and the presence of the SERT short (S)-allele has been shown to mediate the association between maternal stress exposure and ASD. In a mouse model, we investigated the effects of prenatal stress exposure and maternal SERT genotype on offspring behavior and explored its association with maternal microRNA (miRNA) expression during pregnancy. Pregnant female mice were divided into four groups based on genotype (wildtype or SERT heterozygous knockout (Sert-het)) and the presence or absence of chronic variable stress (CVS) during pregnancy. Offspring behavior was assessed at 60 days old (PD60) using the three-chamber test, open field test, elevated plus-maze test, and marble-burying test. We found that the social preference index (SPI) of SERT-het/stress offspring was significantly lower than that of wildtype control offspring, indicating a reduced preference for social interaction on social approach, specifically for males. SERT-het/stress offspring also showed significantly more frequent grooming behavior compared to wildtype controls, specifically for males, suggesting elevated repetitive behavior. We profiled miRNA expression in maternal blood samples collected at embryonic day 21 (E21) and identified three miRNAs (mmu-miR-7684-3p, mmu-miR-5622-3p, mmu-miR-6900-3p) that were differentially expressed in the SERT-het/stress group compared to all other groups. These findings suggest that maternal SERT genotype and prenatal stress exposure interact to influence offspring behavior, and that maternal miRNA expression late in pregnancy may serve as a potential marker of a particular subtype of ASD pathogenesis. |
| first_indexed | 2024-03-10T22:34:07Z |
| format | Article |
| id | doaj.art-6e2e9d9ed410478f9ecdb1af009497cf |
| institution | Directory Open Access Journal |
| issn | 2075-4426 |
| language | English |
| last_indexed | 2024-03-10T22:34:07Z |
| publishDate | 2023-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Journal of Personalized Medicine |
| spelling | doaj.art-6e2e9d9ed410478f9ecdb1af009497cf2023-11-19T11:31:53ZengMDPI AGJournal of Personalized Medicine2075-44262023-09-01139141210.3390/jpm13091412microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine ModelTaeseon Woo0Candice King1Nick I. Ahmed2Madison Cordes3Saatvika Nistala4Matthew J. Will5Clark Bloomer6Nataliya Kibiryeva7Rocio M. Rivera8Zohreh Talebizadeh9David Q. Beversdorf10Interdisciplinary Neuroscience Program, University of Missouri, Columbia, MO 65211, USADepartment of Biological Science, University of Missouri, Columbia, MO 65211, USADepartment of Psychological Sciences, University of Missouri, Columbia, MO 65211, USADepartment of Biological Science, University of Missouri, Columbia, MO 65211, USARock Bridge High School, Columbia, MO 65203, USADepartment of Psychological Sciences, University of Missouri, Columbia, MO 65211, USAGenomics Core, University of Kansas Medical Center, Kansas City, KS 66160, USACollege of Bioscience, Kansas City University, Kansas City, MO 64106, USADivision of Animal Sciences, University of Missouri, Columbia, MO 65211, USAAmerican College of Medical Genetics and Genomics, Bethesda, MD 20814, USAInterdisciplinary Neuroscience Program, University of Missouri, Columbia, MO 65211, USAAutism Spectrum Disorder (ASD) has been associated with a complex interplay between genetic and environmental factors. Prenatal stress exposure has been identified as a possible risk factor, although most stress-exposed pregnancies do not result in ASD. The serotonin transporter (SERT) gene has been linked to stress reactivity, and the presence of the SERT short (S)-allele has been shown to mediate the association between maternal stress exposure and ASD. In a mouse model, we investigated the effects of prenatal stress exposure and maternal SERT genotype on offspring behavior and explored its association with maternal microRNA (miRNA) expression during pregnancy. Pregnant female mice were divided into four groups based on genotype (wildtype or SERT heterozygous knockout (Sert-het)) and the presence or absence of chronic variable stress (CVS) during pregnancy. Offspring behavior was assessed at 60 days old (PD60) using the three-chamber test, open field test, elevated plus-maze test, and marble-burying test. We found that the social preference index (SPI) of SERT-het/stress offspring was significantly lower than that of wildtype control offspring, indicating a reduced preference for social interaction on social approach, specifically for males. SERT-het/stress offspring also showed significantly more frequent grooming behavior compared to wildtype controls, specifically for males, suggesting elevated repetitive behavior. We profiled miRNA expression in maternal blood samples collected at embryonic day 21 (E21) and identified three miRNAs (mmu-miR-7684-3p, mmu-miR-5622-3p, mmu-miR-6900-3p) that were differentially expressed in the SERT-het/stress group compared to all other groups. These findings suggest that maternal SERT genotype and prenatal stress exposure interact to influence offspring behavior, and that maternal miRNA expression late in pregnancy may serve as a potential marker of a particular subtype of ASD pathogenesis.https://www.mdpi.com/2075-4426/13/9/1412serotoninmicroRNAstressautism spectrum disorderSERT |
| spellingShingle | Taeseon Woo Candice King Nick I. Ahmed Madison Cordes Saatvika Nistala Matthew J. Will Clark Bloomer Nataliya Kibiryeva Rocio M. Rivera Zohreh Talebizadeh David Q. Beversdorf microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine Model Journal of Personalized Medicine serotonin microRNA stress autism spectrum disorder SERT |
| title | microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine Model |
| title_full | microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine Model |
| title_fullStr | microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine Model |
| title_full_unstemmed | microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine Model |
| title_short | microRNA as a Maternal Marker for Prenatal Stress-Associated ASD, Evidence from a Murine Model |
| title_sort | microrna as a maternal marker for prenatal stress associated asd evidence from a murine model |
| topic | serotonin microRNA stress autism spectrum disorder SERT |
| url | https://www.mdpi.com/2075-4426/13/9/1412 |
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