Perinatal Lead (Pb) Exposure Increases Mouse Embryonic Weight and Alters Neuronal Gene Expression
Year: 2025
Type: preprint
Abstract: ABSTRACT Acute and chronic exposure to lead (Pb) during pregnancy is linked to adverse health outcomes, including delayed neurodevelopment in offspring. However, the pathways by which Pb exposure influences long-term health remain poorly understood. To address this, we measured the effects of perinatal Pb exposure on gene expression including imprinted genes, X-linked genes, and sexually dimorphic genes. Female mice were given control or Pb acetate dosed (32 ppm) drinking water two weeks prior to timed mating until embryonic day (E)10–12, upon which whole embryos were collected, weighed, and sexed at E13–15. From a subset of embryo heads ( n ≥9 per sex per group), we extracted and sequenced RNA. We used linear regression to assess Pb impacts on embryonic weight and gene expression across all mice and stratified by sex. Among the differentially expressed genes, we identified significantly enriched pathways. Pb-exposed embryos weighed more than controls ( p =0.007), across both sexes. Collectively, we identified 2,920 differentially expressed genes (FDR<0.05), including 31 imprinted genes and 120 X-linked genes upon Pb exposure. Pb exposure altered expression in gene pathways related to neuronal structure and function as well as sexually dimorphic genes (44 for females; 76 for males). These findings highlight perinatal Pb-linked alterations that may drive later-life health outcomes.
Authors: Bambarendage P. U. Perera, Minghua Li, Anagha Tapaswi, Junru Pan, Dongyue Wang, Tejas Goswami, Rachel K. Morgan, Kelly M. Bakulski, Jaclyn M. Goodrich, Maureen A. Sartor, Dana C. Dolinoy, Justin A. Colacino
Institutions: University of Michigan, University of California, Berkeley
Language: English
Subfield: Health, Toxicology and Mutagenesis
Field: Environmental Science
Domain: Physical Sciences
Open Access status: green
Awards: G3280454038, G5543110103, G5614138626, Environmental Epigenomics and Precision Environmental Health, Michigan Nutrition Obesity Research Center, The impact of metals and polygenic risk on multiomics, brain aging, and ADRD outcomes, Michigan Center on Lifestage Environmental Exposures and Disease (M-LEEaD), Imprinted Gene Regulation by in utero Lead Exposure in Mice, Risk of Alzheimer's Disease and Related Dementias from Perinatal Lead Exposure: Brain Region and Cell Type Effects
OpenAlex ID: W4414379256