Grant: Travel Awards - Institute Community Support

We are now aware that pregnancy complications leading to low oxygen delivery (hypoxia) to the fetus increases susceptibility to later-life cardiovascular disease in the offspring. A hypoxic environment within a mother's womb is thought to lead to placental dysfunction (placental oxidative stress) and abnormal cardiac development. This could be due to the release of factors by the placenta into the fetal circulation. Moreover, our laboratory previously showed that treating the placenta against oxidative stress with antioxidants (which reduce production of harmful molecules) improved cardiac function later in life in offspring born from hypoxic pregnancies. The advantage of this placenta-targeted treatment strategy is that it prevents passage across the placenta and avoids direct drug exposure to the fetus in order to avoid off-target effects during development. We recently showed that placental circulating factors from the hypoxic placenta impaired fetal neuronal development, which was prevented by placental antioxidant treatment. The research in the current study focuses on how placental treatment with antioxidants can affect fetal cardiac development. We cultured fetal cardiac cells from rats and incubated them with placental media containing circulating factors to understand effects of these factors on cardiac cell development. We found that factors released from the hypoxic placentae negatively altered normal cardiac development to a different extent in male versus female offspring. We also showed that our placental treatment may contribute to preventing abnormal increases in cardiac cell size but only in male offspring. Our findings indicate that factors released from hypoxic placenta impair fetal cardiac cell growth, which was improved by our placental antioxidant treatment. Most importantly, sex differences need to be taken into account to develop therapeutic strategies for offspring from hypoxic pregnancies.