An Adaptive Response through N6-Methyladenosine in Fetal Offspring following Gestational Nano-TiO2 Inhalation Exposure II

Background: N6-methyladenosine (m6A) is the most prominent epitranscriptomic modification to RNA in eukaryotes, but it's role in adaptive changes within the gestational environment are poorly understood. Nano titanium dioxide (TiO2) exposure is common during pregnancy, though the impact fetal progeny is not entirely understood. We propose that gestational exposure to nano-TiO2 contributes to cardiac m6A methylation in fetal offspring and indirectly contributes to mitochondrial dysfunction. Overall design: Results: 10-week-old pregnant female FVB/NJ wild type mice (n=14) on gestational day (GD) 5 underwent 6 non-consecutive days of whole-body inhalation exposure. Mice were exposed to filtered room air or nano-TiO2 with a target aerosol mass concentration of 12 mg/m3. At GD 15 mice were sacrificed and cardiac RNA and mitochondrial proteins extracted. There were no differences in maternal or fetal pup weights, number of pups, or pup heart weight between exposure and control groups. Immunoprecipitation with m6A antibodies was performed followed by sequencing of immunoprecipitant (m6A) and input (mRNA) on the Illumina NextSeq 2000.