They now believe that the lack of a single protein may lead to the immune system mistakenly identifying a developing foetus as a foreign invader and targeting it for destruction.
Working with mice, the researchers have identified an immune system protein called Crry which appears to play a crucial role in ensuring that babies are not killed before birth.
This protein is thought to de-activate a part of the mother's immune system to stop it attacking the developing embryo.
Similar proteins are suspected of playing the same role in humans.
A team from Washington University School of Medicine in St Louis, US, has shown that mice bred to lack Crry are unable to give birth to live young.
Instead, their immune system unleashes a destructive attack on the tissues of the developing foetus, which are dismantled and reabsorbed by the mother - the equivalent of a miscarriage in humans.
The researchers discovered that Crry blocks a branch of the mother mouse's body defences called the complement system, which helps destroy foreign material such as infectious organisms.
Crry prevents two other "complement" proteins from marking out cells for immune system destruction.
The researchers studied the cell make-up of foetuses growing in the mice that lacked Crry.
Activated for destruction
They found that by the seventh day of gestation both the outer cells of the embryo and the cells of the developing placenta carried activated complement proteins.
They also found that immune system cells called neutrophils had invaded the complement-targeted tissue.
After 10 days it was clear that the immune system was destroying the embryos.
Dr Molina said: "Without this single molecule, complement components of the mouse immune system are activated, resulting in embryonic death."
The researchers, who reported their findings in the journal Science today, now plan to investigate the role of similar proteins in women's miscarriages.
Two placental proteins perform the same duties as Crry in humans - decay accelerating factor and membrane cofactor protein.
Their role in miscarriages has not been previously addressed.
Dr Molina said: "Using the mouse studies as a framework, we can jump to human studies and see whether miscarriages in women also involve complement regulation."
The work will focus on women who have auto-immune diseases such as lupus erythematosus and multiple miscarriages.
The team will try to determine whether such women have reduced levels of the Crry-like regulatory proteins, and might benefit from receiving them artificially.
Dr Gill Vince, an expert in miscarriage from Liverpool University, said most spontaneous abortions were a one off, but a small group of women suffered repeated miscarriages, around 60% of which were unexplained.
She said: "Any breakthrough in explaining repeated miscarriages is good, but it can be difficult to extrapolate from mice to humans as they have different placental systems."
Related to this story:
- Miscarriage risk of slow eggs (10 Jun 99 Health)
- Genetic miscarriage risk (13 Jan 00 Health)
- Caffeine blamed for miscarriages (25 Nov 99 Health)
- Couples 'need more support after miscarriage' (02 Sep 99 Health)
- Miscarriage prevention therapy 'does not work' (30 Jul 99 Health)
Science Washington University School of Medicine Miscarriage links
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