Enhanced antioxidant capacity prevents epitranscriptomic and cardiac alterations in adult offspring gestationally-exposed to ENM
| Autor: | Krista L Garner, Andrew D. Taylor, Andrya J. Durr, Timothy R. Nurkiewicz, John M. Hollander, Mark V. Pinti, William T. Goldsmith, Quincy A. Hathaway, Amina Kunovac |
|---|---|
| Rok vydání: | 2021 |
| Předmět: |
Adult
Bioenergetics Offspring Biomedical Engineering 02 engineering and technology 010501 environmental sciences Biology Toxicology GPX4 01 natural sciences Antioxidants Article Andrology chemistry.chemical_compound Fetus Pregnancy Humans Phospholipid-hydroperoxide glutathione peroxidase 0105 earth and related environmental sciences Inhalation exposure Heart Environmental exposure 021001 nanoscience & nanotechnology Nanostructures chemistry Maternal Exposure Prenatal Exposure Delayed Effects Gestation Female 0210 nano-technology |
| Zdroj: | Nanotoxicology |
| ISSN: | 1743-5404 |
| Popis: | Maternal engineered nanomaterial (ENM) exposure during gestation has been associated with negative long-term effects on cardiovascular health in progeny. Here, we evaluate an epitranscriptomic mechanism that contributes to these chronic ramifications and whether overexpression of mitochondrial phospholipid hydroperoxide glutathione peroxidase (mPHGPx) can preserve cardiovascular function and bioenergetics in offspring following gestational nano-titanium dioxide (TiO2) inhalation exposure. Wild-type (WT) and mPHGPx (Tg) dams were exposed to nano-TiO2 aerosols with a mass concentration of 12.01 ± 0.50 mg/m3 starting from gestational day (GD) 5 for 360 mins/day for 6 nonconsecutive days over 8 days. Echocardiography was performed in pregnant dams, adult (11-week old) and fetal (GD 14) progeny. Mitochondrial function and global N6-methyladenosine (m6A) content were assessed in adult progeny. MPHGPx enzymatic function was further evaluated in adult progeny and m6A-RNA immunoprecipitation (RIP) was combined with RT-qPCR to evaluate m6A content in the 3′-UTR. Following gestational ENM exposure, global longitudinal strain (GLS) was 32% lower in WT adult offspring of WT dams, with preservation in WT offspring of Tg dams. MPHGPx activity was significantly reduced in WT offspring (29%) of WT ENM-exposed dams, but preserved in the progeny of Tg dams. M6A-RIP-qPCR for the SEC insertion sequence region of mPHGPx revealed hypermethylation in WT offspring from ENM-exposed WT dams, which was thwarted in the presence of the maternal transgene. Our findings implicate that m6A hypermethylation of mPHGPx may be culpable for diminished antioxidant capacity and resultant mitochondrial and cardiac deficits that persist into adulthood following gestational ENM inhalation exposure. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|