NMR spectroscopy has revealed that a chemical compound found in unpasteurised food can be present at unusually high levels in the red blood cells of pregnant women. The compound, ergothioneine, could be used as a biomarker for the potentially fatal condition, pre-eclampsia, which can cause severely raised blood pressure during pregnancy.

Women can suffer pre-eclampsia during pregnancy or just after their baby is born, it is associated with high blood pressure and protein in the urine as well as fluid retention. Usually, it is a relatively mild condition, causing headache, abdominal pain, decreased urine output, swelling of the hands and face, nausea, and vomiting. But, it can also cause more serious growth problems in some babies, and if left untreated can develop into full-blown eclampsia, which leads to seizures and is potentially lethal.

Pre-eclampsia affects almost one in ten pregnancies after twenty weeks of gestation. Understanding the aetiology of pre-eclampsia and its progression during pregnancy could help medical researchers develop new approaches to preventing it.

Now, scientists at the University of Leeds have taken blood samples from a group of thirty-seven pregnant women to try and find new clues about the nature of pre-eclampsia. They used Carr-Purcell-Meiboom-Gill (CPMG) proton NMR spectroscopy to compare chemical biomarkers in the red blood cells from women with pre-eclampsia to those from pregnant women without any symptoms.

The researchers then applied multivariate analysis and logistic regression to differentiate between the two groups of patients. They developed a diagnostic model based on the concentrations of the most influential constituents of the samples.

In their study, published in the journal Reproductive Sciences, the chemists reveal that there is a significantly higher concentration of ergothioneine in the red blood cells of women with pre-eclampsia than in those without the condition. The amino acids alanine, glycine, and histidine (an imidazole-based molecule related to ergothioneine) were also found at higher levels in those with the condition than in controls.

Thus, say the researchers, discriminant analysis and regression of NMR data have permitted them to perform an entirely accurate diagnosis of whether or not new patients has pre-eclampsia or not. These results are important because they suggest that the compound, ergothioneine, is an indicator of pre-eclampsia. It may also help scientists to understand what causes the condition.

Ergothioneine is a well-known natural product made by fungi present in foods before they are pasteurised, including dairy products. It is not produced in humans, so its only entry point to the body is through our diet. Previously, research studies on animals have suggested that ergothioneine, rather than being detrimental to health, may actually have a beneficial effect.

"These results suggest that a higher level of ergothioneine is an indicator of pre-eclampsia," explains Leeds chemist Julie Fisher. "Ergothionine is an antioxidant and therefore should be beneficial," Fisher told SpectroscopyNOW, "What we think is happening is the body is storing this in response to signals of excess oxidants - so it is a signal that something is wrong in redox processes rather than causing the condition or necessarily being a symptom."

Ergothioneine have been proposed to be helpful in reducing the risk of pre-eclampsia. It is therefore very interesting that the team should have found it to be in excess for women with the condition.
Fisher cautions that the advice not to eat unpasteurised foods still holds for pregnant women. She recalls being advised not to eat unpasteurised foods when she was pregnant and notes that everyone she knows has avoided such foods and that seems to be the current advice for newly expectant mothers.

James Walker, Professor of Obstetrics at the Leeds Institute of Molecular Medicine and a co-author of the research papers adds, "The high concentration of ergothioneine in the red blood cells of women with pre-eclampsia is a very interesting finding - the more we know about the chemicals involved in the disease the closer we get to understanding what causes it."

Endothelial dysfunction and abnormal placentation are thought to be the primary cause of the disease underpinned by the attack of reactive oxygen species on lipids, which causes protein damage and changes to cell membranes. The discovery of a link with ergothioneine provides an important clue as to the biochemistry of this condition.

Fisher, Walker, and their colleagues Elizabeth Turner, Jennifer Brewster, and Nigel Simpson were supported in their research by the UK's Engineering and Physical Sciences Research Council (EPSRC) and the Medical Research Council (MRC).

Related links:

• Reproductive Sci, 2009, in press
• Fisher Page

Article by David Bradley

The views represented in this article are solely those of the author and do not necessarily represent those of John Wiley and Sons, Ltd.