Gastrulation-stage alcohol exposure induces similar rates of craniofacial malformations in male and female C57BL/6J mice.

Autor: Boschen KE; Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Department of Neuroscience and Physiology, SUNY Upstate Medical University, Syracuse, NY, USA., Dragicevich CJ; Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Fish EW; Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Hepperla AJ; Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Simon JM; Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; UNC Neuroscience Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Department of Genetics, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA., Parnell SE; Bowles Center for Alcohol Studies, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Carolina Institute for Developmental Disabilities, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.; Department of Cell Biology and Physiology, The University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
Jazyk: angličtina
Zdroj: Birth defects research [Birth Defects Res] 2024 Jan; Vol. 116 (1), pp. e2292. Date of Electronic Publication: 2023 Dec 20.
DOI: 10.1002/bdr2.2292
Abstrakt: Background: Prenatal alcohol exposure during gastrulation (embryonic day [E] 7 in mice, ~3rd week of human pregnancy) impairs eye, facial, and cortical development, recapitulating birth defects characteristic of Fetal Alcohol Syndrome (FAS). However, it is not known whether the prevalence or severity of craniofacial features associated with FAS is affected by biological sex.
Methods: The current study administered either alcohol (2.9 g/kg, two i.p. doses, 4 hr apart) or vehicle to pregnant C57BL/6J females on E7, prior to gonadal sex differentiation, and assessed fetal morphology at E17.
Results: Whereas sex did not affect fetal size in controls, alcohol-exposed females were smaller than both control females and alcohol-treated males. Alcohol exposure increased the incidence of eye defects to a similar degree in males and females. Together, these data suggest that females might be more sensitive to the general developmental effects of alcohol, but not effects specific to the craniofacies. Whole transcriptomic analysis of untreated E7 embryos found 214 differentially expressed genes in females vs. males, including those in pathways related to cilia and mitochondria, histone demethylase activity, and pluripotency.
Conclusion: Gastrulation-stage alcohol induces craniofacial malformations in male and female mouse fetuses at similar rates and severity, though growth deficits are more prevalent females. These findings support the investigation of biological sex as a contributing factor in prenatal alcohol studies.
(© 2023 Wiley Periodicals LLC.)
Databáze: MEDLINE
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