English (United Kingdom)

https://curated-unify.zendy.io/wp-json/zendy-region/v1/featured_content/oa?rat=en

https://curated-unify.zendy.io/wp-json/zendy-region/v1/highlighted_journal/

Global: Zendy Plus annual

Presents the access of premium content as premium feature

Premium Content

Presents the keyphrase highlighting as premium feature

Keyphrase Highlighting

Presents the summarisation as premium feature

Summarisation

Insights

Presents the pdf analysis as premium feature

PDF Analysis

Presents the zaia usage as premium feature

ZAIA

Global: Zendy Tools annual

Global: Zendy Free Plan

Global: Zendy Tools monthly

Global: Zendy Plus monthly

Pregnancy complications associated with chronic fetal hypoxia have been linked to the development of adult cardiovascular disease in the offspring. Prenatal hypoxia has been shown to increase placental oxidative stress and impair placental function in a sex-specific manner, thereby affecting fetal development. As oxidative stress is central to placental dysfunction, we developed a placenta-targeted treatment strategy using the antioxidant MitoQ encapsulated into nanoparticles (nMitoQ) to reduce placental oxidative/nitrosative stress and improve placental function without direct drug exposure to the fetus in order to avoid off-target effects during development. We hypothesized that, in a rat model of prenatal hypoxia, nMitoQ prevents hypoxia-induced placental oxidative/nitrosative stress, promotes angiogenesis, improves placental morphology, and ultimately improves fetal oxygenation. Additionally, we assessed whether there were sex differences in the effectiveness of nMitoQ treatment. Pregnant rats were intravenously injected with saline or nMitoQ (100 μl of 125 μM) on gestational day (GD) 15 and exposed to either normoxia (21% O 2 ) or hypoxia (11% O 2 ) from GD15 to 21. On GD21, placentae from both sexes were collected for detection of superoxide, nitrotyrosine, nitric oxide, CD31 (endothelial cell marker), and fetal blood spaces,  Vegfa  and  Igf2  mRNA expression in the placental labyrinth zone. Prenatal hypoxia decreased male fetal weight, which was not changed by nMitoQ treatment; however, placental efficiency (fetal/placental weight ratio) decreased by hypoxia and was increased by nMitoQ in both males and females. nMitoQ treatment reduced the prenatal hypoxia-induced increase in placental superoxide levels in both male and female placentae but improved oxygenation in only female placentae. Nitrotyrosine levels were increased in hypoxic female placentae and were reduced by nMitoQ. Prenatal hypoxia reduced placental  Vegfa  and  Igf2  expression in both sexes, while nMitoQ increased  Vegfa  and  Igf2  expression only in hypoxic female placentae. In summary, our study suggests that nMitoQ treatment could be pursued as a potential preventative strategy against placental oxidative stress and programming of adult cardiovascular disease in offspring exposed to hypoxia  in utero . However, sex differences need to be taken into account when developing therapeutic strategies to improve fetal development in complicated pregnancies, as nMitoQ treatment was more effective in placentae from females than males.

Sex-Specific Effects of Nanoparticle-Encapsulated MitoQ (nMitoQ) Delivery to the Placenta in a Rat Model of Fetal Hypoxia