ASPG and DAD1 are potential placental-derived biomarkers for ASD-like symptom severity levels in male/female offspring

Placenta. 2024 Sep 26:155:78-87. doi: 10.1016/j.placenta.2024.08.009. Epub 2024 Aug 14.

Abstract

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.

Keywords: ASPG; Autism spectrum disorder; DAD1; Placental-derived biomarkers; Sex difference.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Apoptosis Regulatory Proteins* / genetics
  • Apoptosis Regulatory Proteins* / metabolism
  • Asparaginase* / genetics
  • Asparaginase* / metabolism
  • Autism Spectrum Disorder* / metabolism
  • Biomarkers / metabolism
  • Female
  • Male
  • Membrane Proteins* / genetics
  • Membrane Proteins* / metabolism
  • Mice
  • Mice, Inbred C57BL
  • Placenta* / metabolism
  • Placenta* / pathology
  • Pregnancy
  • Severity of Illness Index

Substances

  • Apoptosis Regulatory Proteins
  • Biomarkers
  • Dad1 protein, mouse
  • Membrane Proteins
  • Asparaginase