Details

Autor(en) / Beteiligte

• Ganguly, Esha
• Kirschenman, Raven
• Spaans, Floor
• Holody, Claudia D.
• Phillips, Thomas E. J.
• Case, C. Patrick
• Cooke, Christy‐Lynn M.
• Murphy, Michael P.
• Lemieux, Hélène
• Davidge, Sandra T.

Titel

Nanoparticle‐encapsulated antioxidant improves placental mitochondrial function in a sexually dimorphic manner in a rat model of prenatal hypoxia

Ist Teil von

• The FASEB journal, 2021-02, Vol.35 (2), p.e21338-n/a

Ort / Verlag

United States

Erscheinungsjahr

2021

Link zum Volltext

Quelle

Wiley Online Library - AutoHoldings Journals

Beschreibungen/Notizen

• 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.