Pre-eclampsia 鈥� a condition that strikes 5% of pregnancies and kills over 60,000 women and hundreds of thousands of babies every year 鈥� was once so mysterious that doctors dubbed it the 鈥渄isease of theories鈥�. Now, a team of researchers says that a single gene could explain most cases.
If their work in mice pans out for human childbirth, could be diagnosed earlier and even prevented by giving expecting mums a naturally occurring breakdown product, says , a researcher at Beth Isreal Deaconess Medical Center in Boston, who led the study.
His team showed that mice without a gene that makes a compound broken-down from oestrogen called 2-methoxyestradiol (2-ME) develop many of the signs of pre-eclampsia, including pre-term birth, high blood pressure and problems forming blood vessels.
Advertisement
鈥淭he difference sets the ball rolling and a million other things downstream go wrong,鈥� Kalluri says.
Medical mystery
A major cause of premature deliveries, pre-eclampsia strikes suddenly and often severely. After 20 weeks or longer, women develop high blood pressure and high levels of protein in their urine 鈥� a sign of kidney failure. Currently the only way to treat the disease is to deliver the child 鈥� often weeks early.
Previous studies pointed to abnormal blood vessel growth that starves a developing placenta of oxygen, but researchers had little clue what set off those changes.
鈥淣obody really knows what cause pre-eclampsia,鈥� says Kalluri 鈥淚t has been one of the biggest mysteries in medicine.鈥�
Kalluri鈥檚 team noticed that mice missing a gene that makes 2-ME had one of the hallmarks of pre-eclampsia 鈥� protein in their urine. The mutant mice also showed elevated levels of two blood vessel proteins that have turned up in pre-eclampsia patients.
Giving the pregnant rodents an extra dose of 2-ME reversed many of the symptoms.
His team also found that 13 women who had suffered from pre-eclampsia had slightly lower levels of 2-ME in their blood before birth than women who went through a normal pregnancy.
鈥楢lways present鈥�
If researchers verify 2-ME鈥檚 role in pre-eclampsia in humans, the metabolite could help predict and treat the disease, Kalluri says.
鈥淭he wonderful thing about this metabolite is that it is always present in high levels鈥� during pregnancy, he says. 鈥淚t鈥檚 not like we are giving anything that the baby and the mother are not exposed to.鈥�
To strengthen the case, Kalluri鈥檚 team plans to study pregnant women with mutations that hamper cells from making 2-ME.
鈥淚n some patients with pre-eclampsia, this may well be important,鈥� says James Roberts, a researcher at the University of Pittsburgh. However, one gene alone is unlikely to cause all of the cases, he says.
Treatments may be also premature, says , an epidemiologist and pre-eclampsia expert at the National Institute of Child Health and Human Development in Bethesda, Maryland.
鈥淚t is a provocative and potentially important paper 鈥� if it is confirmed by other labs,鈥� he says.
Journal reference: (DOI: 10.1038/nature06951)
