Perinatal Lead (Pb) Exposure Increases Mouse Embryonic Weight and Alters Neuronal Gene Expression.

Area of Science:

• Environmental Health
• Developmental Biology
• Toxicology

Background:

• Prenatal and early-life lead (Pb) exposure is associated with adverse neurodevelopmental outcomes in children.
• The specific molecular mechanisms by which Pb exposure affects embryonic development and long-term health are not fully understood.

Purpose of the Study:

• To investigate the impact of perinatal lead exposure on gene expression patterns in mouse embryos.
• To identify specific gene categories, including imprinted, X-linked, and sexually dimorphic genes, affected by lead exposure.
• To explore potential pathways linking lead exposure to later-life health issues.

Main Methods:

• Female mice received lead acetate in drinking water before and during early pregnancy.
• Embryos were collected at embryonic day (E)10-12, weighed, and sexed.
• RNA sequencing was performed on a subset of embryo heads (n≥9 per sex per group).
• Linear regression analysis was used to assess the effects of lead on embryonic weight and gene expression, stratified by sex.

Main Results:

• Lead-exposed embryos exhibited increased weight compared to controls (p=0.007).
• A total of 2,920 differentially expressed genes (FDR<0.05) were identified, including 31 imprinted and 120 X-linked genes.
• Lead exposure altered the expression of genes involved in neuronal structure and function.
• Sexually dimorphic gene expression was affected, with 44 genes altered in females and 76 in males.

Conclusions:

• Perinatal lead exposure significantly alters embryonic gene expression, impacting critical gene categories.
• Changes in imprinted, X-linked, and sexually dimorphic gene expression pathways may underlie lead-induced neurodevelopmental and long-term health effects.
• These findings provide molecular insights into the developmental toxicity of lead exposure.