Journal article
Combined Maternal Exposure to Cypermethrin and Stress Affect Embryonic Brain and Placental Outcomes in Mice
Toxicological sciences, Vol.175(2), pp.182-196
06/01/2020
DOI: 10.1093/toxsci/kfaa040
PMID: 32191333
Abstract
Abstract Prenatal exposure to cypermethrin is a risk factor for adverse neurodevelopmental outcomes in children. In addition, maternal psychological stress during pregnancy has significant effects on fetal neurodevelopment and may influence end-stage toxicity to offspring by altering maternal xenobiotic metabolism. As such, this study examined effects of maternal exposure to alpha-cypermethrin and stress, alone and in combination, on offspring development, with a focus on fetal neurotoxicity. CD1 mouse dams were administered 10 mg/kg alpha-cypermethrin or corn oil vehicle via oral gavage from embryonic day 11 (E11) to E14. In addition, dams from each treatment were subjected to a standard model of restraint stress from E12 to E14. Cypermethrin treatment impaired fetal growth, reduced fetal forebrain volume, and increased ventral forebrain proliferative zone volume, the latter effects driven by combined exposure with stress. Cypermethrin also impaired migration of GABAergic progenitors, with different transcriptional changes alone and in combination with stress. Stress and cypermethrin also interacted in effects on embryonic microglia morphology. In addition, levels of cypermethrin were elevated in the serum of stressed dams, which was accompanied by interacting effects of cypermethrin and stress on hepatic expression of cytochrome P450 enzymes. Levels of cypermethrin in amniotic fluid were below the limit of quantification, suggesting minimal transfer to fetal circulation. Despite this, cypermethrin increased placental malondialdehyde levels and increased placental expression of genes responsive to oxidative stress, effects significantly modified by stress exposure. These findings suggest a role for interaction between maternal exposures to cypermethrin and stress on offspring neurodevelopment, involving indirect mechanisms in the placenta and maternal liver.
Details
- Title: Subtitle
- Combined Maternal Exposure to Cypermethrin and Stress Affect Embryonic Brain and Placental Outcomes in Mice
- Creators
- Benjamin A Elser - Interdisciplinary Graduate Program in Human Toxicology, Graduate College, Department of Psychiatry, Carver College of MedicineKhaled Kayali - Department of Psychiatry, Carver College of MedicineRam Dhakal - Department of Occupational and Environmental HealthBailey O’Hare - Department of Psychiatry, Carver College of MedicineKai Wang - Department of Biostatistics, College of Public Health, The University of Iowa, Iowa City, Iowa 52242Hans-Joachim Lehmler - Interdisciplinary Graduate Program in Human Toxicology, Graduate College, Department of Occupational and Environmental HealthHanna E Stevens - Interdisciplinary Graduate Program in Human Toxicology, Graduate College, Department of Psychiatry, Carver College of Medicine
- Resource Type
- Journal article
- Publication Details
- Toxicological sciences, Vol.175(2), pp.182-196
- DOI
- 10.1093/toxsci/kfaa040
- PMID
- 32191333
- NLM abbreviation
- Toxicol Sci
- ISSN
- 1096-6080
- eISSN
- 1096-0929
- Grant note
- DOI: 10.13039/100011291, name: American College of Toxicology; name: North American Graduate Fellowship; name: University of Iowa Pappajohn Biomedical Institute; name: Microfinance Grant; name: University of Iowa Central Microscopy Research Facility; name: Pilot Project Seed Grant; name: University of Iowa Environmental Health Sciences Research Center; name: EHSRC; name: Pilot Grant and Career Development Award; DOI: 10.13039/100000002, name: NIH, award: P30 ES005605
- Language
- English
- Date published
- 06/01/2020
- Academic Unit
- Psychiatry; Occupational and Environmental Health; Stead Family Department of Pediatrics; Iowa Neuroscience Institute; Biostatistics
- Record Identifier
- 9984000926902771
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