Journal article
Maternal α-cypermethrin and permethrin exert differential effects on fetal growth, placental morphology, and fetal neurodevelopment in mice
Toxicological sciences, Vol.207(1), pp.91-108
09/01/2025
DOI: 10.1093/toxsci/kfaf079
PMCID: PMC12448229
PMID: 40517329
Appears in UI Libraries Support Open Access
Abstract
Pyrethroid insecticides represent a broad class of chemicals used widely in agriculture and household applications. Human studies show mixed effects of maternal pyrethroid exposure on fetal growth and neurodevelopment. Assessment of shared pyrethroid metabolites as a biomarker for exposure obscures effects of specific chemicals within this broader class. To better characterize pyrethroid effects on fetal development, we investigated maternal exposure to permethrin, a type I pyrethroid, and α-cypermethrin, a type II pyrethroid, on fetal development in mice. Pregnant CD1 mice were exposed to permethrin (1.5, 15, or 50 mg/kg), α-cypermethrin (0.3, 3, or 10 mg/kg), or corn oil vehicle via oral gavage on gestational days (GDs) 6 to 16. Effects on fetal growth, placental toxicity, and neurodevelopment were evaluated at GD 16. Cypermethrin, but not permethrin, significantly reduced fetal growth and altered placental layer morphology. Placental RNAseq analysis revealed downregulation of genes involved in extracellular matrix remodeling in response to α-cypermethrin. Both pyrethroids induced shifts in fetal dorsal forebrain microglia morphology from ramified to ameboid states; however, the effects of α-cypermethrin were more pronounced. The α-cypermethrin transcriptome of fetal dorsal forebrain implicated altered glutamate receptor signaling, synaptogenesis, and c-AMP signaling. Coregulated gene modules in individual placenta and fetal dorsal forebrain pairs were correlated and overlapped in biological processes characterizing synapses, mitotic cell cycle, and chromatin organization, suggesting placenta-fetal brain shared mechanisms with α-cypermethrin exposure. In summary, maternal exposure to the type II pyrethroid α-cypermethrin, but not type I pyrethroid permethrin, significantly affected placental development, fetal growth, and neurodevelopment, and these effects were linked.
Details
- Title: Subtitle
- Maternal α-cypermethrin and permethrin exert differential effects on fetal growth, placental morphology, and fetal neurodevelopment in mice
- Creators
- Benjamin A Elser - University of IowaBenjamin Hing - University of IowaSamuel Eliasen - University of IowaMalik A Afrifa - University of IowaNaomi Meurice - University of IowaFarzana Rimi - University of IowaMichael Chimenti - University of IowaLaura C Schulz - University of MissouriMichael E Dailey - University of IowaKatherine N Gibson-Corley - Vanderbilt University Medical CenterHanna E Stevens - University of Iowa
- Resource Type
- Journal article
- Publication Details
- Toxicological sciences, Vol.207(1), pp.91-108
- DOI
- 10.1093/toxsci/kfaf079
- PMID
- 40517329
- PMCID
- PMC12448229
- NLM abbreviation
- Toxicol Sci
- ISSN
- 1096-0929
- eISSN
- 1096-0929
- Publisher
- Oxford University Press
- Grant note
- Center for Health Effects of Environmental Contamination P30 ES005605 / NIH HHS University of Iowa's Pappajohn Biomedical Institute University of Iowa Environmental Health Sciences Research Center Microfinance Research University of Iowa's National Institute for Environmental Health Sciences NIEHS
- Language
- English
- Electronic publication date
- 05/30/2025
- Date published
- 09/01/2025
- Academic Unit
- Molecular Physiology and Biophysics; Psychiatry; The University of Iowa Institute for Vision Research; Iowa Neuroscience Institute; Biology; Iowa Institute of Human Genetics
- Record Identifier
- 9984832187302771
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