Fast-ageing placentas may explain pre-eclampsia risks

For women diagnosed with pre-eclampsia, the only cure is often to deliver the baby – even if the pregnancy has not yet reached full term.

Pre-eclampsia affects up to 8% of pregnancies worldwide and contributes to about 16% of maternal deaths globally, making the condition one of pregnancy's most serious complications.

New research led by Flinders University, in collaboration with the Robinson Research Institute at Adelaide University, has uncovered clues about why pre-eclampsia occurs, finding that a placenta may age prematurely. Researchers have also identified the biological pathways that could eventually help protect mothers and babies.

Lead author Dr Anya Arthurs from Flinders Health and Medical Research Institute says the study goes beyond identifying a damaged placenta to explain what may cause that damage.

“Rather than being simply a consequence of disease, placental ageing may be an important process that contributes to pre-eclampsia. Understanding what drives this process gives us new opportunities to explore ways of protecting placental function and improve outcomes for mothers and babies,” says Dr Arthurs.

“Previous research has linked placental ageing to pregnancy complications, but we wanted to understand the processes causing a placenta to age prematurely.

“Our findings identify key biological pathways involved in this process and highlight possible targets for future treatments.”

The placenta acts as a baby's lifeline during pregnancy, supplying oxygen and nutrients while removing waste. When it is not functioning properly, the risks to both mother and baby increase significantly.

For this investigation, researchers examined placental tissue from healthy pregnancies and pregnancies affected by late onset pre-eclampsia. They also used laboratory-grown mini-placentas, known as trophoblast organoids, to explore the condition in greater detail.

The team found that placentas affected by pre-eclampsia showed several signs of accelerated ageing, including increased DNA damage, shortened telomeres that protect chromosomes, and a build-up of aged cells that no longer function normally.

Researchers identified oxidative stress as a major contributor to these changes. Oxidative stress occurs when harmful molecules accumulate faster than the body's natural defences can remove them, causing damage to cells and tissues.

“When oxidative stress increases, placental cells accumulate damage that appears to accelerate the ageing process. What we found particularly encouraging was that reducing oxidative stress in our laboratory models lessened several markers of placental ageing,” says Dr Arthurs.

The study also revealed an important role for molecules known as telomeric repeat-containing RNAs, or TERRAs, which help protect chromosome ends and maintain healthy cell function.

Researchers found lower levels of these molecules in placentas affected by pre-eclampsia, and when TERRA levels were reduced in laboratory models, signs of cellular ageing became even more pronounced.

While further research is needed before any new therapies can be used during pregnancy, the researchers say these new findings help pinpoint biological pathways that may eventually lead to better prevention of difficulties, earlier identification of at-risk pregnancies and improved care.