Cell-type and fetal-sex-specific targets of prenatal alcohol exposure in developing mouse cerebral cortex. Academic Article uri icon


  • Prenatal alcohol exposure (PAE) results in cerebral cortical dysgenesis. Single-cell RNA sequencing was performed on murine fetal cerebral cortical cells from six timed pregnancies, to decipher persistent cell- and sex-specific effects of an episode of PAE during early neurogenesis. We found, in an analysis of 38 distinct neural subpopulations across 8 lineage subtypes, that PAE altered neural maturation and cell cycle and disrupted gene co-expression networks. Whereas most differentially regulated genes were inhibited, particularly in females, PAE also induced sex-independent neural expression of fetal hemoglobin, a presumptive epigenetic stress adaptation. PAE inhibited Bcl11a, Htt, Ctnnb1, and other upstream regulators of differentially expressed genes and inhibited several autism-linked genes, suggesting that neurodevelopmental disorders share underlying mechanisms. PAE females exhibited neural loss of X-inactivation, with correlated activation of autosomal genes and evidence for spliceosome dysfunction. Thus, episodic PAE persistently alters the developing neural transcriptome, contributing to sex- and cell-type-specific teratology.

published proceedings

  • iScience

altmetric score

  • 6.95

author list (cited authors)

  • Salem, N. A., Mahnke, A. H., Konganti, K., Hillhouse, A. E., & Miranda, R. C.

citation count

  • 16

complete list of authors

  • Salem, Nihal A||Mahnke, Amanda H||Konganti, Kranti||Hillhouse, Andrew E||Miranda, Rajesh C

publication date

  • May 2021