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Developmental Biology - Mitochondria
Placentas Can Adapt To Poor Diets/Low Oxygen
The placenta regulates how much oxygen and nutrients it sends to babies...
St. John's College, University of Cambridge in the United Kingdom researchers have discovered how the placenta regulates oxygen and nutrients it transports to babies during challenged pregnancies. Using mice, researchers recreated conditions in the womb to observe various outcomes.
The placenta is women's least understood organ as it is notoriously difficult to study in pregnancy. But, its ability to function properly is vital as it impacts the health of both mother and child. It develops in pregnancy to connect the neonate to its mother, serving as it's lungs, kidneys, gut and liver, carrying oxygen and nutrients to the fetus, secreting hormones and discarding waste. The study is published in the Proceedings of the National Academy of Sciences (PNAS).
Researchers analyzed placental cells called mitochondria. These are the energy powerhouses found in most cells of our body. They use oxygen to convert sugars and fat into energy.
"The study analyzed how lacental mitochondria might alter their function to support both the needs of the placenta to support the rapidly growing fetus during a healthy pregnancy, even when the mother is challenged by a less desirable environment.
"We found placenta mitochondria have a remarkable ability to adapt and compensate for environmental impacts such as living in low oxygen at high altitude, not eating enough, or poor diet during pregnancy."
Amanda Sferruzzi-Perri PhD, Center for Trophoblast Research, Department of Physiology, Development and Neuroscience, University of Cambridge, United Kingdom.
Changing lifestyles in vastly expanding society find women consuming nutritionally deficient diets during pregnancy which can cause pregnancy complications. Also, living at high altitudes above 2500m in places such as Bolivia, Peru, Tibet and Ethiopia, can restrict fetal oxygen. It is estimated that approximately two per cent of the human population - 140 million people - live in areas with low oxygen.
Under such conditions, the placenta can't always function properly causing miscarriage, preeclampsia and/or fetal growth restriction. Around 10 per cent of babies are born with fetal growth restriction, leaving the fetus with life long health problems.
Fetal growth restriction is a strong marker for increased risk of stillbirth or death in the first weeks of life. Long term, it can lead to cerebral palsy, behavioural and developmental issues, neurological disorders, as well as chronic heart disease, obesity and diabetes later in a child's life.
To examine placental outcomes, scientists introduced challenges such as hypoxic conditions in laboratory mice. Between our two species, our placentas develop and function in similar ways. Researchers explored how placental mitochondria react under stress and what impact this has on fetal growth.
"Mitochondria in the placenta work out how to use oxygen and nutrients in the most efficient way so there is still sufficient energy transfered to the fetus in challenged pregnancies. When the placenta cannot compensate for the challenges, then this can lead to complications such as fetal growth restriction.
"We know that there is a lasting impact on the health of babies born with fetal growth restriction because organs and tissues like the heart, pancreas, muscles, and liver, are very sensitive when developing. If those organs don't grow properly they are more likely to malfunction in later life."
Amanda N. Sferruzzi-Perri PhD.
The aim of the study, the first of its kind, is to understand what's required for a healthy placenta to perform its vital function.
When babies are born with fetal growth restriction, the team previously found the placental buffering mechanism was insufficient during pregnancy.
Hopefully, these new findings will lead to effective tests to determine what is optimal placental functioning and eventually lead to new treatments to restore placental function.
"Our next step will be to target mitochondria in the placenta, alter their function and improve pregnancy success in women where the outcome might be poor."
Amanda N. Sferruzzi-Perri PhD.
Significance
Mitochondria are the primary source of ATP for placental growth, transport, and hormone synthesis. However, to date, little is known about the developmental regulation or functional significance of placental mitochondria during normal or suboptimal intrauterine conditions, such as oxygen deprivation (hypoxia). Here we show that, in the placenta, mitochondria adapt their use of oxygen and nutrients (carbohydrate and fat) to best support both placental growth and function, as well as fetal development, during normal and hypoxic conditions. These data are significant because they improve our mechanistic understanding of human pregnancies compromised by fetal growth restriction at sea level and high altitude.
Abstract
Mitochondria respond to a range of stimuli and function in energy production and redox homeostasis. However, little is known about the developmental and environmental control of mitochondria in the placenta, an organ vital for fetal growth and pregnancy maintenance in eutherian mammals. Using respirometry and molecular analyses, the present study examined mitochondrial function in the distinct transport and endocrine zones of the mouse placenta during normal pregnancy and maternal inhalation hypoxia. The data show that mitochondria of the two zones adopt different strategies in modulating their respiration, substrate use, biogenesis, density, and efficiency to best support the growth and energy demands of fetoplacental tissues during late gestation in both normal and hypoxic conditions. The findings have important implications for environmentally induced adaptations in mitochondrial function in other tissues and for compromised human pregnancy in which hypoxia and alterations in placental mitochondrial function are associated with poor outcomes like fetal growth restriction.
Authors
Amanda N. Sferruzzi-Perri, Josephine S. Higgins, Owen R. Vaughan, Andrew J. Murray and Abigail L. Fowden
Acknowledgments
This work was funded by a PhD studentship (to J.S.H.), an in vivo skills Award BB/F016581/1 (to A.N.S.-P. and A.L.F.) from the British Biotechnology and Biological Sciences Research Council, and a Next Generation Fellowship (to A.N.S.-P.) and PhD studentship (to O.R.V.) from the Centre for Trophoblast Research.
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Nov 18 2019 Fetal Timeline Maternal Timeline News
Analyzing mouse placentas, researchers found their mitochondria have the ability to adapt and compensate for negative environmental impacts. CREDIT MouseWorks Inc.
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