A hormone secreted by the placenta during pregnancy may play a key role in the development of pre-eclampsia; a major worldwide cause of maternal and fetal death.
A*STAR researchers first discovered the hormone, called ELABELA, or ELA, in 2013 and showed, in zebrafish, that it was essential for normal embryonic development of the heart and cardiovascular system. Further work revealed that, in mammals, ELA was produced by the placenta, and when administered to rats and mice, caused their blood pressure to drop.
“So if you consider the two — a hormone specifically expressed in the placenta, that has blood pressure-lowering properties — one would expect that its absence would trigger gestational hypertension, a key symptom of pre-eclampsia,” says Bruno Reversade, research director at the A*STAR Institute of Medical Biology.
In this new international study led by A*STAR, researchers crossed male and female mice that each carried only one copy of the ELA-coding gene to produce ‘knockout’ mice. Around half of these knockout mice showed severe embryonic cardiovascular malformations and did not survive to birth. Despite their inability to produce ELA, the other half did survive.
But when the female knockout mice grew to adulthood and became pregnant, they showed high blood pressure and protein in their urine, classic signs of pre-eclampsia, while their fetuses also had the lower birth weight typical of babies born to mothers with the condition.
However, Reversade says the most exciting discovery of the research was that treating the pregnant knockout female mice with ELA hormone reversed their pre-eclampsia symptoms and increased the birth weight of their offspring.
“We have uncovered a completely new signaling pathway, a hormone and its receptor, in the pathogenesis of pre-eclampsia. Because it’s a hormone, it could be developed into a drug as is insulin for diabetes,” Reversade says.
This discovery also opens up the possibility of using ELA, or more specifically the observation of lower ELA levels, to enable early diagnosis of pre-eclampsia, which affects 5–8 per cent of all pregnancies.
“One of the biggest unmet needs in the field is that we don’t have early predictive diagnostic biomarkers of when a woman is susceptible to develop pre-eclampsia,” Reversade says.
Researchers are now examining this hormone in humans, starting with a study comparing ELA levels in pregnant women with pre-eclampsia and those with normal blood pressure.
The A*STAR-affiliated researchers contributing to this research are from the Institute of Medical Biology and the Institute of Molecular and Cell Biology. For more information about the team’s research, please visit the Reversade Group webpage.
Ho, L., van Dijk, M., Tan Jian Chye, S., Messerschmidt, D. M., Chng, S. C. et al. ELABELA deficiency promotes pre-eclampsia and cardiovascular malformations in mice. Science 357, 707–713 (2017) | Article