This research aims to assess the concentration of metals in human and canine placentas from the same geographic area and to investigate how these metal levels influence gene expression within the placenta. Placentas of 25 dogs and 60 women who had recently given birth residing in Ankara, Turkey were collected and subjected to metal analysis using ICP-OES. Placentas with detectable metal levels underwent further examination including Next Generation Sequencing, transcriptional analysis, single nucleotide polymorphism investigation, and extensive scrutiny across various groups. For women, placentas with concurrent detection of aluminum (Al), lead (Pb), and cadmium (Cd) underwent transcriptomic analysis based on metal analysis results. However, the metal load in dog placentas was insufficient for comparison. Paired-end sequencing with 100-base pair read lengths was conducted using the DNBseq platform. Sequencing quality control was evaluated using FastQC, fastq screen, and MultiQC. RNA-sequencing data is publicly available via PRJNA936158. Comparative analyses were performed between samples with detected metals and “golden” samples devoid of these metals, revealing significant gene lists and read counts. Normalization of read counts was based on estimated size factors. Principal Component Analysis (PCA) was applied to all genes using rlog-transformed count data. Results indicate that metal exposure significantly influences placental gene expression, impacting various biological processes and pathways, notably those related to protein synthesis, immune responses, and cellular structure. Upregulation of immune-related pathways and alterations in protein synthesis machinery suggest potential defense mechanisms against metal toxicity. Nonetheless, these changes may adversely affect placental function and fetal health, emphasizing the importance of monitoring and mitigating environmental exposure to metals during pregnancy.