Summary: A new study reports statins could help protect the hearts of babies while in the womb from maternal stress.
Source: University of Edinburgh.
Statins could protect the hearts of babies in the womb from the adverse effects of their mother’s stress, research suggests.
Scientists have discovered that the widely-prescribed drugs help to counteract the negative impact of stress hormones on fetal growth and heart development in mice.
The therapy could lower the chances of babies being born underweight and reduce their risk of health problems in later life, including heart disease, researchers say.
Further studies are needed to assess the long-term effects of statins in pregnancy, but the drugs are already used occasionally in pregnant women and should be suitable for clinical trials, the team says.
“Although more work needs to be done to show statins are safe in human pregnancy, these results show a new way forward for the major unmet need of fetal growth retardation,” said Professor Megan Holmes.
Babies that are exposed to excessive stress hormones in the womb are often born underweight and have a greater risk of heart disease in later life.
Normally, the unborn baby is protected by a key enzyme produced by the placenta that breaks down stress hormones and greatly limits the amount of active hormones that reach the baby’s blood supply.
When the expectant mother is stressed, they produce less of this enzyme and the baby is less well protected.
Scientists at the University of Edinburgh studied mice that cannot produce the enzyme as a model of maternal stress.
They found that stress hormones stop the placenta from developing normal blood vessels, which cuts back the blood supply to the growing fetus.
The developing fetus does not grow to full size as a result, and its heart function does not develop normally.
Treating the mother with a type of statin triggers production of a molecule called VEGF, which stimulates the development of blood vessels in the placenta.
By re-establishing the blood supply, the treatment promotes normal development of the heart and helps the baby to grow to a healthy birthweight, the team showed.
“How Pravastatin counteracts the stress hormone is not yet understood, therefore more research is needed to see whether the drug will have the same effect in humans.” Said Professor Jeremy Pearson, Associate Medical Director of the British Heart Foundation.
Around 2.5 million people in the UK take statins to lower high cholesterol.
About this genetics research article
Funding: The study is published in the journal Proceedings of the National Academy of Sciences and was funded by the Wellcome Trust. The research also received funding from the Raine Medical Research Foundation, University of Western Australia.
Source:University of Edinburgh Image Source: This NeuroscienceNews.com image is in the public domain. Original Research:Abstract for “Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess” by Caitlin S. Wyrwoll, June Noble, Adrian Thomson, Dijana Tesic, Mark R. Miller, Eva A. Rog-Zielinska, Carmel M. Moran, Jonathan R. Seckl, Karen E. Chapman, and Megan C. Holmes in PNAS. Published online May 16 2016 doi:10.1073/pnas.1520356113
Cite This NeuroscienceNews.com Article
[cbtabs][cbtab title=”MLA”]University of Edinburgh. “Statins May Curb Effects of Stress in the Womb.” NeuroscienceNews. NeuroscienceNews, 16 May 2016. <https://neurosciencenews.com/maternal-stress-statins-4233/>.[/cbtab][cbtab title=”APA”]University of Edinburgh. (2016, May 16). Statins May Curb Effects of Stress in the Womb. NeuroscienceNews. Retrieved May 16, 2016 from https://neurosciencenews.com/maternal-stress-statins-4233/[/cbtab][cbtab title=”Chicago”]University of Edinburgh. “Statins May Curb Effects of Stress in the Womb.” https://neurosciencenews.com/maternal-stress-statins-4233/ (accessed May 16, 2016).[/cbtab][/cbtabs]
Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess
Fetoplacental glucocorticoid overexposure is a significant mechanism underlying fetal growth restriction and the programming of adverse health outcomes in the adult. Placental glucocorticoid inactivation by 11β-hydroxysteroid dehydrogenase type 2 (11β-HSD2) plays a key role. We previously discovered that Hsd11b2−/− mice, lacking 11β-HSD2, show marked underdevelopment of the placental vasculature. We now explore the consequences for fetal cardiovascular development and whether this is reversible. We studied Hsd11b2+/+, Hsd11b2+/−, and Hsd11b2−/− littermates from heterozygous (Hsd11b+/−) matings at embryonic day (E)14.5 and E17.5, where all three genotypes were present to control for maternal effects. Using high-resolution ultrasound, we found that umbilical vein blood velocity in Hsd11b2−/− fetuses did not undergo the normal gestational increase seen in Hsd11b2+/+ littermates. Similarly, the resistance index in the umbilical artery did not show the normal gestational decline. Surprisingly, given that 11β-HSD2 absence is predicted to initiate early maturation, the E/A wave ratio was reduced at E17.5 in Hsd11b2−/− fetuses, suggesting impaired cardiac function. Pravastatin administration from E6.5, which increases placental vascular endothelial growth factor A and, thus, vascularization, increased placental fetal capillary volume, ameliorated the aberrant umbilical cord velocity, normalized fetal weight, and improved the cardiac function of Hsd11b2−/− fetuses. This improved cardiac function occurred despite persisting indications of increased glucocorticoid exposure in the Hsd11b2−/− fetal heart. Thus, the pravastatin-induced enhancement of fetal capillaries within the placenta and the resultant hemodynamic changes correspond with restored fetal cardiac function. Statins may represent a useful therapeutic approach to intrauterine growth retardation due to placental vascular hypofunction.
“Pravastatin ameliorates placental vascular defects, fetal growth, and cardiac function in a model of glucocorticoid excess” by Caitlin S. Wyrwoll, June Noble, Adrian Thomson, Dijana Tesic, Mark R. Miller, Eva A. Rog-Zielinska, Carmel M. Moran, Jonathan R. Seckl, Karen E. Chapman, and Megan C. Holmes in PNAS. Published online May 16 2016 doi:10.1073/pnas.1520356113