Preprint
Maternal α-cypermethrin and permethrin exert differential effects on fetal growth, placental morphology, and fetal neurodevelopment in mice
bioRxiv
Cold Spring Harbor Laboratory, 1.1
03/17/2025
DOI: 10.1101/2025.03.16.643434
PMCID: PMC11956951
PMID: 40166261
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 (GD) 6-16. 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, 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 type II pyrethroid α-cypermethrin exposure 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 - Department of Psychiatry, Carver College of Medicine, The University of IowaSamuel Eliasen - Department of Psychiatry, Carver College of Medicine, The University of IowaMalik A. Afrifa - Department of Psychiatry, Carver College of Medicine, The University of IowaNaomi Meurice - Department of Psychiatry, Carver College of Medicine, The University of IowaFarzana Rimi - Graduate College, The 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 - Department of Psychiatry, Carver College of Medicine, The University of Iowa
- Resource Type
- Preprint
- Publication Details
- bioRxiv
- Edition
- 1.1
- DOI
- 10.1101/2025.03.16.643434
- PMID
- 40166261
- PMCID
- PMC11956951
- NLM abbreviation
- bioRxiv
- ISSN
- 2692-8205
- eISSN
- 2692-8205
- Publisher
- Cold Spring Harbor Laboratory
- Number of pages
- 54
- Language
- English
- Date posted
- 03/17/2025
- 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
- 9984805005602771
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