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Placenta pivotal in influencing pregnancy outcome
For the first time, research has shown how the placenta "umpires" a fight for nutrients between a pregnant mother and her unborn baby. The study suggests that the placenta will adjust the amount of nutrients transported to the fetus for growth in line with the mother's physical ability to supply them.
Published in the journal PNAS, the findings suggest that if the environment a mother provides for her baby is unfavourable, the placenta will change the flow of nutrients to the fetus relative to her state, affecting fetal development, and can result in complications at birth.
The study, by researchers at the University of Cambridge, involved making a precise genetic change in mice, which caused poor growth and changed the mother's bodily environment. They then observed how the placenta developed and acted in response, finding that in mothers in which this alteration had been made, the structure of the placenta was different, and fewer nutrients reached the fetus.
A better understanding of how the placenta manages the trade-off will eventually enable researchers to reduce pregnancy complications in both humans and other mammals.
The study is part of a five-year project in the Department of Physiology, Development and Neuroscience examining the relationship between the placenta and pregnancy complications. It was led by Dr Amanda Sferruzzi-Perri, a Research Associate at St John's College, University of Cambridge, in the United Kingdom.
"During pregnancy there is a kind of 'tug-of-war' going on between the mother and the fetus over who gets the nutrients that the mother ingests," adds Sferruzzi-Perri. "This work shows for the first time that the placenta is the umpire which controls that fight. Understanding more about the placenta's role is extremely important. If nutrients cannot be divided correctly during pregnancy, it can lead to life-threatening complications for expectant mothers, and long-term health consequences for both mother and child."
But how the placenta allocates nutrients in these situations, and hormonal signals that the placenta may be releasing, are not yet fully understood. Better understanding these processes, researchers hope to identify early biological warnings that a problem has arisen, these warnings as they relate to specific causes, and enable medical therapeutic interventions to reduce complications.
The new study represents a step towards these aims as researchers were able to directly influence the balancing act the placenta performs, and observe it relative to both the physiology of the mother, and the actual growth and nutrient supply to the fetus.
Working with mice as their model system, researchers genetically modified an enzyme called p110 alpha in pregnant mice. In a healthy mouse, this enzyme is activated by hormones such as insulin and insulin-growth factors (IGFs), to kick-start a relay race inside cells stimulating nutrient uptake, resulting in normal growth and metabolic function. By altering p110 alpha enzyme, researchers reduced the mouse mother's overall responsiveness to such hormones, creating an unfavourable placental environment.
The research also reflected what would happen to the placenta if the fetus carried the altered form of p110 alpha, while the mother was normal. In those cases the placenta also showed defects, but was able to compensate by transporting more nutrients to the fetus, thus optimising pup nutrition.
This was the first demonstration that the placenta will fine-tune distribution of nutrients between mother and fetus in response to its own altered circumstances. It also indicates that the placenta will optimise fetal nutrition, so that the mother's health is not compromised — as a mother needs to support her baby both during pregnancy and after birth.
The next phase of research will examine signals sent by the placenta to the mother regarding the nutrients she ingests, potentially illuminating important biomarkers providing an early warning of pregnancy complications.
Dr Sferruzzi-Perri's research is supported by a Dorothy Hodgkin Fellowship from the Royal Society. Her paper, "Maternal and fetal genomes interplay through phosphoinositol 3-kinase(PI3K)-p110α signalling to modify placental resource allocation," is published in PNAS.
Research suggests if the environment a mother provides her babies is unfavourable,
the placenta will change the flow of nutrients in favor of the fetus. But can complicate birth.
Image Credit: Public domain.