Nanoparticle‐encapsulated antioxidant improves placental mitochondrial function in a sexually dimorphic manner in a rat model of prenatal hypoxia
| العنوان: | Nanoparticle‐encapsulated antioxidant improves placental mitochondrial function in a sexually dimorphic manner in a rat model of prenatal hypoxia |
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| المؤلفون: | Floor Spaans, C. Patrick Case, Christy-Lynn M. Cooke, Raven Kirschenman, Esha Ganguly, Claudia D. Holody, Sandra T. Davidge, Michael P. Murphy, Thomas E. Phillips, Hélène Lemieux |
| المصدر: | The FASEB Journal. 35 |
| بيانات النشر: | Wiley, 2021. |
| سنة النشر: | 2021 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, Ubiquinone, Placenta, Cell Respiration, Biology, Fetal Hypoxia, medicine.disease_cause, Mitochondrial Dynamics, Biochemistry, Antioxidants, Rats, Sprague-Dawley, Andrology, 03 medical and health sciences, chemistry.chemical_compound, Organophosphorus Compounds, Sex Factors, 0302 clinical medicine, Pregnancy, Genetics, medicine, Animals, Molecular Biology, Fetus, MitoQ, Hypoxia (medical), Mitochondria, Rats, 030104 developmental biology, medicine.anatomical_structure, Mitochondrial biogenesis, chemistry, mitochondrial fusion, embryonic structures, Nanoparticles, Gestation, Female, medicine.symptom, 030217 neurology & neurosurgery, Oxidative stress, Biotechnology |
| الوصف: | Pregnancy complications associated with prenatal hypoxia lead to increased placental oxidative stress. Previous studies suggest that prenatal hypoxia can reduce mitochondrial respiratory capacity and mitochondrial fusion, which could lead to placental dysfunction and impaired fetal development. We developed a placenta-targeted treatment strategy using a mitochondrial antioxidant, MitoQ, encapsulated into nanoparticles (nMitoQ) to reduce placental oxidative stress and (indirectly) improve fetal outcomes. We hypothesized that, in a rat model of prenatal hypoxia, nMitoQ improves placental mitochondrial function and promotes mitochondrial fusion in both male and female placentae. Pregnant rats were treated with saline or nMitoQ on gestational day (GD) 15 and exposed to normoxia (21% O2 ) or hypoxia (11% O2 ) from GD15-21. On GD21, male and female placental labyrinth zones were collected for mitochondrial respirometry assessments, mitochondrial content, and markers of mitochondrial biogenesis, fusion and fission. Prenatal hypoxia reduced complex IV activity and fusion in male placentae, while nMitoQ improved complex IV activity in hypoxic male placentae. In female placentae, prenatal hypoxia decreased respiration through the S-pathway (complex II) and increased N-pathway (complex I) respiration, while nMitoQ increased fusion in hypoxic female placentae. No changes in mitochondrial content, biogenesis or fission were found. In conclusion, nMitoQ improved placental mitochondrial function in male and female placentae from fetuses exposed to prenatal hypoxia, which may contribute to improved placental function. However, the mechanisms (ie, changes in mitochondrial respiratory capacity and mitochondrial fusion) were distinct between the sexes. Treatment strategies targeted against placental oxidative stress could improve placental mitochondrial function in complicated pregnancies. |
| تدمد: | 1530-6860 0892-6638 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::dc42e5c1eaaa1b7506bd67bd215bcd3dTest https://doi.org/10.1096/fj.202002193rTest |
| حقوق: | CLOSED |
| رقم الانضمام: | edsair.doi.dedup.....dc42e5c1eaaa1b7506bd67bd215bcd3d |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15306860 08926638 |
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