Intrauterine growth restriction (IUGR) and preeclampsia (PE) are common and life-threatening complications for mothers and babies. Currently there are no effective treatments other than delivery of the baby. We postulate that angiotensin converting enzyme 2 (ACE2) is important in protecting against placental inflammation and oxidative stress, preventing PE and IUGR.
We have recently shown that ACE2 is abundant in the healthy human placenta and soluble ACE2 levels are elevated in pregnancy but its expression is reduced in pregnancies complicated by IUGR and in the circulation of women with PE. ACE2 is well known to have protective roles in counterbalancing the vasoconstrictor, pro-inflammatory and oxidative stress inducing arm of the renin-angiotensin system (RAS), which is mediated by angiotensin II (Ang II), however its protective actions in pregnancy have not yet been explored.
Reduced placental production of ACE2 as seen in IUGR and, for example, as a result of nutritional deficiency, stress or COVID-19 infection, is associated with placental inflammation and oxidative stress and thus may contribute to the pathogenesis of IUGR and PE. ACE2 is the receptor for the novel coronavirus, SARS-CoV-2, which causes COVID-19. Since SARS-CoV-2 decreases placental expression of ACE2, further investigation into the consequences of COVID-19 infection in the mother and her fetus are needed. Not only do women with COVID-19 infection during pregnancy have worse respiratory outcomes but they are also more likely to develop gestational hypertension and PE. Furthermore, the risk of low birth weight and intrauterine fetal distress is increased.
We propose that loss of the protective actions of ACE2 causes placental inflammation, oxidative stress, fetal growth restriction and maternal hypertension. Therefore, recombinant ACE2 or activation of the ACE2-mediated RAS pathways could be potential treatments for PE and IUGR and for preventing PE and IUGR in pregnant women with COVID-19.