杏吧原创

ONE OF THE great mysteries of the human condition is what makes us, unlike
most other animals, spend such an inordinate amount of time having sex . . . and
so little time actually getting pregnant.

Nor is this a new phenomenon that came along with contraception. Couples
still have plenty of sex when conception is out of the question either because
of the time of the woman鈥檚 cycle, or because she is already pregnant or
breastfeeding.

But now the mystery of these fruitless bonkings might be solved. According to
reproductive biologists at the University of Adelaide in South Australia, far
from being an exercise in futility, plenty of sex鈥攅ven up to a full year
before conception鈥攈elps guard against a litany of ailments. And Puritans
prepare to be shocked鈥攆ellatio may work just as well as missionary-style
intercourse.

The disorders, which range from infertility to high blood pressure during
pregnancy, all appear to be linked to the reluctance of the mother鈥檚 immune
system to accept the fetus and placenta, both of which come armed with an
arsenal of foreign proteins courtesy of the father鈥檚 genes. Sex, early and
often, and with the intended father, may help overcome that reluctance, say the
Adelaide team.

Clearly, if the mother鈥檚 immune system remains unconvinced the consequences
will be dire. She may immediately and repeatedly reject new embryos鈥攊n
which case, she鈥檚 infertile. If her immune system takes a little longer to shun
the foreign tissue, she may suffer frequent miscarriages. And if the rejection
is milder still it might only affect the placenta鈥攁lthough even that can
be a disaster. The placenta is the fetus鈥檚 lifeline, supplying oxygen and
nutrients from the mother鈥檚 blood. If the placenta fails to grow, or becomes
clogged with angry immune cells, the supply line is cut, and an underweight baby
is the result or even a stillbirth.

Immune rejection can even threaten the mother鈥檚 life. According to one still
controversial theory, it鈥檚 the mother鈥檚 rejection of the placenta that causes
pre-eclampsia, a condition where the mother鈥檚 blood pressure soars, in some
cases triggering convulsions, coma and death. In this frightening scenario,
fragments of dead placental cells are swept into the mother鈥檚 circulation, where
they damage vessels, sending her blood pressure skywards.

鈥淚t鈥檚 just different expressions of one underlying theme,鈥� says Gustaaf
Dekker, a member of the Adelaide group. 鈥淲e see patients that have two
miscarriages, then they finally manage to get through their miscarriage period,
and they have pre-eclampsia, or the placenta detaches and they have a stillbirth
at 24 weeks.鈥�

It鈥檚 easy to understand why the mother鈥檚 immune system might be tempted to
annihilate that developing fetus. As if having foreign genes weren鈥檛 bad enough,
the fetus behaves brutishly during its stay in the womb. Its placenta invades
the wall of the uterus like a cancer, infiltrating a nearby artery to guarantee
steady supplies of oxygen and nutrients. It also casts millions of foreign cells
adrift in the mother鈥檚 bloodstream, cells that re-attach and grow in places like
her lungs. The mother鈥檚 immune system should positively squash those cells like
cockroaches, but amazingly in normal pregnancies it lets them be.

鈥淎cceptance of the conceptus is a much more dynamic affair than anyone鈥檚 ever
given credit for,鈥� says Rodney Kelly, a reproductive immunologist at the
University of Edinburgh, who strongly suspects that the Adelaide group is on to
something. 鈥淭here鈥檚 fetal cells in the maternal circulation, there鈥檚 plenty of
antigen, [so] there鈥檚 obviously an enormous amount of immune modulation
preventing rejection.鈥�

That process of immune modulation begins with the first drop of semen. You
wouldn鈥檛 suspect it during those dreamy post-coital moments, but for the next 15
hours or so a woman鈥檚 cervix is swarming with immune cells. They swoop in like
government agents investigating an alien crash site鈥攚hich is essentially
what they are doing. They busy themselves collecting the man鈥檚 foreign
proteins鈥攅ven entire sperm cells鈥攁nd lug them back to the lymph
nodes where other immune cells learn to recognise them. Normally those foreign
proteins would end up on the immune system鈥檚 Most Wanted list: antibodies would
be made against them, and primed to annihilate the sperm next time they dared to
darken their doorstep. But the miracle of sex is that semen contains not only
millions of sperm loaded with foreign proteins, but also some recently
discovered components that tilt a woman鈥檚 immune response away from hostility
and toward acceptance.

鈥淚f there鈥檚 repeated exposure to that signal,鈥� says Dekker, 鈥渢hen eventually
when the woman conceives, her [immune] cells will say, `we know that guy, he鈥檚
been around a long time, we鈥檒l allow the pregnancy to continue.'鈥�

Of course acceptance of the sperm by the mother鈥檚 immune system isn鈥檛 all
that鈥檚 needed for a straightforward pregnancy. But when things do go wrong,
sperm have the power to provoke a vicious immune response. Following
intercourse, women very occasionally go into anaphylactic shock, an immune
response so severe that breathing can be nigh on impossible, and blood pressure
plummets dangerously low. For these luckless women, just a drop of semen on a
thigh can raise boils. The problem appears to stem from lacklustre attempts by
the woman鈥檚 immune system to become tolerant to sperm, combined with the man鈥檚
semen doing a really bad job of convincing it. In some cases switching partners
is all it takes to solve the problem.

And there鈥檚 other tantalising evidence of semen鈥檚 power over the mother鈥檚
immune response. An analysis of pre-eclampsia patterns in 1.7 million births
from the Medical Birth Registry of Norway found that certain 鈥渄angerous males鈥�
are nearly twice as likely to father a pre-eclamptic pregnancy. These dangerous
males carry their high risk from one female partner to the next.

But these are the rare examples where a man鈥檚 semen isn鈥檛 functioning
properly. It was Pierre-Yves Robillard, a neonatologist now at the Sud
R茅union Hospital on R茅union in the Indian Ocean, who showed that
under normal circumstances semen exposure actually helps prevent
pre-eclampsia鈥� evidence that flies in the face of mainstream explanations
for the disorder such as the popular 鈥減antyhose鈥� theory.

According to this theory, pre-eclampsia develops not because the mother鈥檚
immune system sees the placenta as foreign, but because the blood vessels that
supply the placenta don鈥檛 expand enough. The placenta runs short of oxygen, and
once again dying cells push up the woman鈥檚 blood pressure. By a second pregnancy
the blood vessels are already widened like worn pantyhose, which is why, say the
textbooks, pre-eclampsia usually only happens in a first pregnancy. According to
Robillard鈥檚 studies, however, later pregnancies can be just as risky under
certain circumstances.

In the late 1980鈥檚, Robillard was on the French island of Guadeloupe in the
Caribbean, a territory dotted with sugar and banana plantations, where families
are often made up of a single woman who has several children by different men.
There he made the curious discovery that most of his patients with pre-eclampsia
were actually on their second or third pregnancy. But it was specifically the
women who had changed partners since their last pregnancy who were developing
the condition. Robillard speculated that the mother鈥檚 immune system requires
time (and contact with semen) to learn to accept the father鈥檚 foreign genes and
not attack the placenta and cause pre-eclampsia. Changing fathers between
pregnancies 鈥減uts your counter back at zero immunologically speaking鈥�, he
says.

He confirmed his hunch in his next study of 1011 pregnant women on
Guadeloupe. Women who had sex with the father for 12 months or more before
getting pregnant had a 5 per cent chance of developing pre-eclampsia compared to
a massive 40 per cent chance for those who鈥檇 only been having sex with the
father for four months or less. What鈥檚 more, another study found that using
condoms, which naturally prevent women from coming into contact with semen,
increases the risk of pre-eclampsia.

Robillard鈥檚 studies make an excellent case for the medicinal virtues of semen
exposure. But it was Dekker, then at the Free University of Amsterdam, who took
the studies one eyebrow-raising step further when he looked to see if the same
goal could be achieved with oral sex鈥攐r more specifically, fellatio.

It鈥檚 well known that our immune systems tolerate things better when they
enter the body via the mouth. This is why we鈥檙e not usually allergic to our food
even though it鈥檚 always genetically foreign, and why girls with nickel braces on
their teeth are less likely to develop nickel allergies after their ears are
pierced than girls without these braces.

Sure enough, when Dekker compared 41 pregnant women with pre-eclampsia and 44
without, he found that 82 per cent of those without pre-eclampsia practised
fellatio, compared with only 44 per cent of those with the disorder. And in
keeping with the 鈥渃ondom effect鈥�, the protective effect of oral sex was
strongest if the woman actually swallowed the semen rather than coughing it onto
the pillow. True, it鈥檚 only one study, but for some couples who can鈥檛 seem to
carry a pregnancy to term, a little fellatio can hardly do any harm, suggests
Dekker. 鈥淚 tell them, 鈥榮emen exposure鈥檚 good, and you could think of oral
蝉别虫.'鈥�

Some people are a little less gung-ho. 鈥淭he idea is cool,鈥� says James
Roberts, director of the Magee-Women鈥檚 Research Institute at the University of
Pittsburgh, 鈥渂ut generating data that鈥檚 not confounded is very difficult because
sexual practices aren鈥檛 independent of one another.鈥� The couples indulging in
oral sex might, for example, have more sex overall.

Sure they could, acknowledges Dekker, 鈥渂ut even then it still supports the
same message鈥攖hat semen exposure is protective.鈥�

Roberts also points out a potential weakness in Robillard鈥檚 father-switching
data from Guadeloupe: it鈥檚 possible that pregnancies with new partners tend to
happen longer after the last pregnancy than those with the same father, which
might mean that increased pre-eclampsia is triggered not by lack of exposure to
semen, but by the stress of re-expanding uterine blood vessels that have shrunk
back down since the last pregnancy. Still, this is just a minor quibble. 鈥淭here
are other ways to read the data,鈥� says Roberts, but there鈥檚 nothing that holds
together quite as well as the idea of immune rejection contributing to
pre-eclampsia, and semen exposure preventing it.

If you are wondering whether the exhortation for fellatio is a case of male
fantasies hijacking science, as one New 杏吧原创 editor thought,
consider that the Adelaide group is spearheaded by a woman鈥攔eproductive
biologist Sarah Robertson.

Robertson and obstetrician Kelton Tremellen have already helped
show that one component of semen
(see graphic)
plays a key role in persuading the mother鈥檚
immune system to accept foreign sperm and a foreign fetus鈥攁 discovery that
could lead to medical treatments that are more refined than your basic fellatio.
鈥淲e might be able to devise artificial therapies to augment natural intercourse
or maybe even replace natural intercourse in people who have problems getting
this immune thing going on their own,鈥� says Robertson.

Their key component is called transforming growth factor beta. TGF-beta
summons immune cells to the woman鈥檚 cervix after sex to gather the man鈥檚 foreign
proteins. And according to Robertson and Tremellen鈥檚 mouse studies, TGF-beta
also acts as a switch, transforming what would usually be a hostile reaction to
sperm from the immune cells into a friendly one. When the two researchers
injected sperm protein into mouse uteruses, then injected the same protein under
the skin of the mice a few days later, it triggered a severe allergic
reaction鈥攗nless the first injection also included TGF-beta.

What makes their discovery particularly exciting as a potential therapy is
that TGF-beta has this effect the first time sperm enter the vagina, although,
says Robertson, repeated exposure to the sperm and TGF-beta is probably
necessary for complete tolerance.

Dekker and Tremellen are currently comparing TGF-beta levels in the semen of
men who have fathered normal pregnancies with the dangerous males where
conception has ended in miscarriages or pre-eclampsia. Their hunch is that
dangerous males simply don鈥檛 sport enough TGF-beta in their semen. If they are
right, the next step will be to treat women who suffer repeated miscarriages or
IVF failures with TGF-beta.

Of course, the TGF-beta will have to be given along with the father鈥檚 foreign
proteins, which means during intercourse, perhaps in a vaginal gel. Intercourse
during an IVF cycle is already known to up the chances of pregnancy (New
杏吧原创, 9 December 2000, p 6). Tremellen suspects that鈥檚 partly due to
the TGF-beta in the semen. The gel, he says, would provide an additional
boost.

Nor are the potential pay-offs to understanding how a woman鈥檚 immune system
tolerates a fetus for nine months confined to reproductive medicine. Autoimmune
diseases such as lupus and multiple sclerosis, where the body鈥檚 immune system
attacks its own organs, are another target. 鈥淭here鈥檚 nothing to say we couldn鈥檛
deliver myelin in a vaginal immunisation that might benefit women with MS,鈥� says
Tremellen.

The Adelaide group鈥檚 work is also satisfying for other reasons more to do
with, eh, lifestyle. After all, it provides validation for what many people
already hoped鈥攖hat all those long, lingering Saturday mornings in the sack
are anything but a wasted effort.