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ASPG and DAD1 are potential placental-derived biomarkers for ASD-like symptom severity levels in male/female
Yi-Xiao Wu1, Ming-Jie Li2, Yue Liu1
1Shanghai-MOST Key Laboratory of Health and Disease Genomics, NHC Key Lab of Reproduction Regulation, Shanghai Institute for Biomedical and Pharmaceutical Technologies, School of Basic Medical Sciences, Fudan University, Shanghai, 200032, China.
Insights
Early detection of autism spectrum disorder (ASD) severity is vital. Placental biomarkers ASPG and DAD1 show potential for assessing ASD-like symptom severity in offspring.
Area of Science:
- Developmental neuroscience
- Biomarker discovery
- Autism spectrum disorder research
Background:
- Accurate early evaluation of autism spectrum disorder (ASD) severity is critical for timely intervention.
- Current methods like questionnaire surveys face challenges in precisely assessing ASD severity in children.
- Investigating placental factors may offer novel insights into ASD pathogenesis and severity assessment.
Purpose of the Study:
- To identify potential placental biomarkers for early evaluation of autism spectrum disorder (ASD) severity.
- To explore the relationship between placental characteristics and ASD-like phenotypes in offspring.
- To investigate the role of placental factors in the sexual dimorphism observed in ASD-like phenotypes.
Main Methods:
- ASD-like phenotypes were induced in mouse offspring via maternal Poly (I:C) treatment.
- Placental morphology was analyzed using HE staining and immunohistochemistry.
- Weighted protein co-expression network analysis (WPCNA) combined with machine learning identified candidate biomarkers.
- Biomarker validation was performed using ELISA, with correlation analysis against behavioral scores and metabolome.
Main Results:
- Male offspring with ASD-like phenotypes exhibited decreased placental weight and mean vascular area.
- Four gene co-expression modules significantly correlated with autism severity composite scores (ASCS) were identified.
- Two key biomarkers, ASPG and DAD1, demonstrated a high correlation with ASCS in offspring.
Conclusions:
- Placental ASPG and DAD1 levels can potentially reflect ASD-like symptom severity in both male and female mouse offspring.
- The VEGF pathway may influence sexual dimorphism in placental morphology in the context of ASD-like phenotypes.
- These findings suggest placental biomarkers as promising tools for early ASD severity assessment.
Introduction:
An early evaluating system for autism spectrum disorder (ASD) severity is crucial. Questionnaire survey is challenging for accurately assessing the severity levels for ASD in children.
Methods:
Offspring with ASD-like phenotypes were induced by treating pregnant mice with Poly (I:C) at GD12.5 and the placentae corresponding to the offspring were obtained by caesarean. The autism severity composite score (ASCS) for offspring was calculated through behavioral tests. HE staining and immunohistochemistry were used to observe the morphology of placenta. Candidate biomarkers were identified by weighted protein co-expression network analysis (WPCNA) combined with machine learning and further validated by ELISA. Sperman's was used to analyze the correlation between biomarkers and metabolome.
Results:
The placental weight and mean vascular area of male offspring with ASD-like phenotypes were significantly decreased compared with typical mice. According to the WPCNA, four modules were identified and significantly correlated with ASCS of offspring. Two biomarkers (ASPG and DAD1) with high correlation with ASCS in offspring were identified.
Discussion:
VEGF pathway may contribute to sexual dimorphism in placental morphology within mice with ASD-like phenotypes in term. The placental ASPG and DAD1 levels could reflect ASD-like symptom severity levels in male/female mice offspring.
