Humans' comparatively huge brains
are, at least for some of us, a successful adaptation
to our natural environment. However, developing this gigantic
brain during pregnancy requires a massive supply of blood,
which involves an extensive remodelling of arteries in
the uterine wall. Inefficient remodelling of these arteries
leads to pre-eclampsia � the worldwide leading cause of
pregnancy-associated mortality. As Dr Peter Parham of
Stanford University explained, "some mortality from pre-eclampsia
is the price paid for increasing brain size and the competitive
advantages that brings." While induced labour remains
the only treatment for this condition, prevention may
soon be possible with a rapid genetic test.
In a study published in the October
18 issue of the Journal of Experimental Medicine,
researchers led by Dr Susan Hiby of Cambridge University
linked pre-eclampsia with cells that normally act in
the immune system. These natural killer (NK) cells are
lymphocytes that need to be turned on by chemical signals
from the fetus in order for efficient vascular remodelling
to occur. When NK cells are inhibited, the resulting
inefficient vascular network between mother and fetus
can lead to the severe maternal hypertension that typifies
pre-eclampsia. Left unchecked, this could progress to
severe convulsions and seizure.
THE
TYPES THAT BIND
The genes of both mother and child were examined in
200 pregnancies complicated by pre-eclampsia and 201
normal pregnancies. Genes that encoded either a strong
or a weak chemical signal were found in the fetuses.
The chemical signal produced seemed to bind to receptors
on mums' NK cells. Two types of receptors were found
when mums' genes were examined. Mothers with pre-eclampsia
had haplotype A receptors while the normal women had
haplotype B. When type A receptors were bound by the
signal, NK cells were inhibited. When the signal was
bound to type B receptors, however, NK cells were activated.
Type A receptors, especially when bound by strong chemical
signals from the fetus, led to poor NK cell activity
and, consequently, pre-eclampsia.
Practically speaking, these findings
suggest that a simple genetic test to determine the
signal and receptor types in mother and child could
give us an accurate prediction of whether a pregnancy
will be complicated with preeclampsia. Interestingly,
Dr Parham suggested in his accompanying commentary that
these results should also help dispel the idea that
the fetus is an adversary of the maternal immune system.
Instead, "a more sensible paradigm is now emerging,
one in which cells and molecules of immunity are part
and parcel of the reproductive process and used in a
constructive manner."
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