Background: Mexico has a high burden of chronic kidney disease (CKD). The state of Aguascalientes is among the regions with the highest reported prevalence of end-stage kidney disease worldwide. In this setting, CKD of unknown etiology predominates and has been associated with a low number of nephrons of prenatal origin. This study examines the DNA methylation profile following maternal exposure to fluoride and its relationship with lower kidney volume in neonates. Methods: This cross-sectional study included at-term pregnant women without concomitant comorbidities. Neonatal total kidney volume (TKV) was calculated using ultrasound imaging. Maternal urine was collected to quantify xenobiotics, and placental DNA methylation was analyzed using the Illumina MethylationEPIC BeadChip. Neonates were classified by TKV percentile low kidney volume (LKV) = percentile 10th, and fluoride (F — ) exposure (F — ≥1.5 mg/L; NF — <1.5mg/L). Bioinformatic analyses were performed to identify differentially methylated genes (DMGs) and enriched biological pathways associated with kidney volume status and fluoride exposure. Results: Thirty-two women were included in the study between March 2023 and April 2024. Principal component analysis (PCA) revealed distinct placental methylation profiles between the groups (LKV/F and CTRL/NF). Epigenome-wide analysis identified 7,540 differentially methylated sites (6,635 hypomethylated and 905 hypermethylated; adjusted p value (FDR)<0.01 and Δβ≥0.1). Integration of stratified comparisons across kidney volume and fluoride exposure identified a shared epigenetic signature of 244 DMGs, including protocadherin clusters and genes related to kidney development, cell adhesion, and developmental signaling. Functional enrichment analyses highlighted pathways involved in calcium signaling, focal adhesion, and organogenesis. Conclusion: Placental DNA methylation profiles associated with neonatal kidney volume were identified in a population with prenatal fluoride exposure. The consistency and biological relevance of the identified epigenetic signature support an association between fluoride exposure and alterations in placental DNA methylation involving pathways critical for early kidney development.
Zúñiga-Macías et al. (Fri,) studied this question.