The utility of resveratrol for improving fetal growth in complicated pregnancies
Chief Investigator: Dr Alison Care
Funding Amount: $74,276
Recipient: University of Adelaide
Impaired fetal growth during pregnancy impacts subsequent health for babies and children, but few interventions can improve fetal growth. Our recent studies suggest that resveratrol, a natural anti-inflammatory compound in red grapes, is a potential agent for improving fetal growth in pregnancy. We will study how resveratrol promotes the function of regulatory T cells, a leukocyte subset crucial for placental function and pregnancy success, that is deficient in many pregnant women. The results will facilitate development of resveratrol as a novel treatment in common obstetric conditions.
Researchers: Alison Care, Sarah Robertson, Sandra Davidge, Lachlan Moldenhauer, Sean O’Leary
Research Completed: 2021
Research Findings: Preeclampsia is a common pregnancy complication that increases lifelong risk of cardiovascular disease in more than 4 million pregnant women and their children each year. We have identified a specialised immune cell in the mother’s blood that helps the blood vessels to function properly in pregnancy, that is deficient in some women with preeclampsia. Our preclinical studies show that by boosting these immune cells, we can improve poor blood vessel function and pregnancy outcomes.
Preeclampsia is a pregnancy-specific syndrome with no effective treatment. It leads to premature births, stillbirth, and lifelong risk of cardiovascular disease in more than 4 million pregnant women and their children every year. There are limited clinical options other than delivery, mainly because the underlying mechanisms remain undefined. This is a major knowledge gap that our research has begun to address. We have identified a specialised immune cell in the mother’s blood that helps the blood vessels to function properly in pregnancy, known as regulatory T (Treg) cells. Many women with
preeclampsia have fewer Treg cells, and there is evidence this has a causal role in disease susceptibility.
Using preclinical mouse models, we have demonstrated that Treg cells are required to facilitate remodelling of blood vessels that supply oxygen and nutrients to the placenta and fetus, known as spiral arteries. When Treg cells are deficient, this remodelling fails, leading to compromised placental development and reduced growth of the fetus.
Our findings provide the first evidence that treatment with Treg cells can rescue spiral artery remodelling, highlighting Treg cells as a promising target to prevent or reduce the severity of preeclampsia. Furthermore, treatment with Treg cells can improve the function of blood vessels that supply nutrients to the uterus, as well as the placenta. As a part of this study, we have begun to investigate other tools to boost Treg cells to help us understand how this affects the development of blood vessels that supply the placenta, and whether these interventions may improve fetal growth. These tools include biological therapies such as resveratrol that target Treg cells to increase their number and anti-inflammatory function, as well as exercise. Our preliminary data has shown for the first time that exercise before and during pregnancy can increase the proportion of Treg cells, and we are currently working to refine the exercise protocol to obtain immune benefits without imposing excessive energy demands on the mother.
- Hosking SL, Groome HM, O’Hara SE, Moldenhauer LM, Davidge ST, Roberts CT, Robertson SA, Care AS. Regulatory T cells support decidual spiral artery remodelling through modulation of uterine natural killer cells in mice.
- Lovell EA, Hosking SL, Gatford KL, Moldenhauer LM, McConell GK, Robertson SA, Care AS. Intensive exercise before and during pregnancy impairs uterine natural killer cell abundance and spiral artery remodelling in mice.
Fully Refereed Conference Proceedings:
- Care AS, Groome HM, Hosking SL, Roberts CT, Davidge ST, Robertson SA (2020) Regulatory T Cells Determine Uterine Natural Killer Cell Abundance and Decidual Vascular Remodeling in Early Pregnancy in Mice. Reproductive Sciences. 2020. Vol 27 (Suppl 1):70A-70A.
- Care AS, Bourque SL, Morton JA, Hjartarson EP, Humphries J, Davidge ST, Robertson SA (2019) Regulatory T cell deficiency increases resistance to uteroplacental blood flow, leading to fetal growth restriction. Reproductive Sciences. 2019 Mar Vol 26:116A-116A.
- Care AS, Bourque SL, Morton JA, Hjartarson EP, Robertson SA, Davidge ST (2018) Regulatory T cells regulate uterine artery function to impact fetal growth. Reproductive Sciences. Vol 25:70A-70A.
Other Conference Presentations:
- Lovell EA, Hosking SL, Gatford KL, Moldenhauer LM, McConell GK, Robertson SA, Care AS (2021) Intensive exercise before and during pregnancy impairs uterine natural killer cell abundance and spiral artery remodelling in mice. ASMR, Adelaide.
- Hosking SL, Groome HM, O’Hara S, Moldenhauer LM, Robertson SA, Care AS (2021) Regulatory T cell depletion impairs decidual spiral artery remodelling and reduces uterine natural killer cell abundance, leading to fetal growth restriction in mice. ASMR, Adelaide.
- Care AS, Groome HM, Davidge ST, Robertson SA (2019) Reduction in regulatory T cell number in early pregnancy impairs decidual artery remodeling and leads to fetal growth restriction. Society for Reproductive Biology, Sydney, Australia.
- Care AS (2021) Regulatory T cells as drivers of placental vascular remodelling in mice. Australian and New Zealand Placental Research Association Virtual Satellite Meeting.
- Care AS (2019) Regulatory T cells modulate maternal vascular adaptations to pregnancy, World Congress of International Society for Immunology of Reproduction (ISIR), Nara, Japan
- Care AS (2018) How Maternal Immune Cells Drive Vascular Adaptations to Pregnancy, Newcastle Award, Society for Reproductive Biology, Finalist, Adelaide, Australia
Care AS (2018) Targeting regulatory T cells in preeclampsia – the key to enhanced vascular adaptations to pregnancy? Australian Preeclampsia Network Annual Meeting, Sydney, Australia.