Researchers have discovered in the journal Proceedings of the National Academy of Sciences (PNAS) that the placenta regulates how much oxygen and nutrients it transports to babies during challenging pregnancies in a study using mice to model conditions in the womb.

The placenta is the least understood organ and is notoriously difficult to study in pregnant women. But its ability to function properly is vital as it impacts on pregnancy outcomes and the lifelong health of mother and child.

The placenta develops during pregnancy and connects the developing baby to the mother. It serves as the lungs, kidneys, gut and liver for growing babies and carries oxygen and nutrients to the fetus whilst secreting hormones and discarding waste.

The lead author said: "The study analysed how mitochondria in the placenta may alter their function to support both the needs of the placenta and the rapidly growing fetus during a healthy pregnancy, and when the mother is challenged by a less desirable environment.

"We found that in the placenta, mitochondria have a remarkable ability to adapt and compensate for environmental impacts such as when women are living in low oxygen areas at high altitude and not eating enough of a healthy diet during pregnancy."

Changing lifestyles in society which see women consuming nutritionally deficient diets during pregnancy can cause pregnancy complications and living at high altitudes above 2500m in places such as Bolivia, Peru, Tibet and Ethiopia restricts oxygen levels. It is estimated that around two per cent of the human population - 140 million people - live in areas with low oxygen.

In these conditions the placenta doesn't always function properly and can cause miscarriage, preeclampsia and fetal growth restriction. Around 10 per cent of babies are born with fetal growth restriction - when the baby doesn't grow properly - and it can leave a lasting legacy on their health.

Fetal growth restriction is a strong marker of potential problems with the baby, including stillbirth, death in the first weeks of life, an increased risk of being born with cerebral palsy, behavioural and developmental issues, neurological disorders and chronic diseases later in life such as heart disease, obesity and diabetes.

The team of scientists introduced challenges - known as hypoxic conditions - in the laboratory. They used the mouse as a model, as its placenta develops and functions in a similar way to humans, looking at how the placenta and their mitochondria reacted and what impact this had on the growth of the fetus.

The 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 lead author explained: "Mitochondria in the placenta work out how to use oxygen and nutrients in the most efficient way so there is still sufficient for transfer to the fetus even in challenged pregnancies. When the placenta cannot compensate for the challenges then this can lead complications such as fetal growth restriction."

The lead author added: "Our findings show mitochondria are really important determinants of placental function and support of fetal growth. The next step would be to target mitochondria in the placenta to alter their function and improve pregnancy success in women where we know the outcome might be poor."

When babies are born with fetal growth restriction, the team had previously found the buffering mechanism of the placenta was insufficient during pregnancy.

It is hoped the new findings could lead to tests to determine whether the placenta is functioning properly and eventually provide treatments where to restore placental function to the right level for a healthy pregnancy outcome.

https://www.joh.cam.ac.uk/placentas-adapt-when-mothers-have-poor-diets-or-low-oxygen-during-pregnancy

https://www.pnas.org/content/early/2019/01/16/1816056116