A Biological Function for Oral Sex?

Sexual priming by a male partner lowers risk of high blood pressure in

pregnancy
Posted Feb 02, 2016

Source: Original cartoon by Alex Martin

Problems with high blood pressure (hypertension) afflict many pregnancies, counting
alongside abortion and haemorrhage as a major cause of maternal death. Worldwide,
more than 18% of pregnancies are affected, roughly half involving pre-eclampsia a
syndrome marked by excess protein in the urine and swollen limbs (oedema). This
typically arises after mid-pregnancy and increases in severity until birth, which is the
only effective remedy. In some cases, especially if untreated, the condition develops
into full-blown, life-threatening eclampsia with seizures and even coma. Roughly one in
ten pre-eclampsia cases develop into the more serious condition of eclampsia. (That
word, derived from a Greek root meaning shine forth, refers to characteristic visual
flashes experienced by sufferers.)

Global causes of maternal death 1997-2007

Source: Adapted from a figure provided by UNICEFs ChildInfo website
(http://www.childinfo.org/facts_1038.htm(link is external))

Women older than 35 are at greater risk of pre-eclampsia, as are those with obesity,
diabetes or previous high blood pressure. It is also more common with first pregnancies
and multiple births. Well-designed prenatal care programmes include routine screening
for pre-eclampsia.
Basic facts about pre-eclampsia
Although overt symptoms typically emerge after mid-pregnancy, pre-eclampsia is
seemingly triggered very early. A 2005 paper by HaiTao Yuan and colleagues aptly
describes it as a 2stage disease: symptomless early processes in the placenta followed
several months later by diagnosable pre-eclampsia. Several factors have been
implicated, but it is widely accepted that inadequate development of blood vessels in the
early placenta plays a major part, often limiting fetal growth in due course. In fact,
significant changes in the womb begin once the egg leaves the ovary. Arteries in the

wombs internal lining lengthen, forming distinctive spirals. The human placenta is very
invasive and maternal blood soon surrounds tree-like outgrowths from the outer fetal
membrane, permitting direct interchange with blood vessels of the fetus. Maternal white
blood cells also abound in the placenta during the first third of pregnancy, reflecting
active engagement of the mothers immune response.

Scheme of human placental circulation

Source: Adapted from illustration in Anatomy of the Human Body (Henry Gray. 1918) by Henry Vandyke Carter,
via Wikimedia Commons.

While travelling down the oviduct towards the womb, the fertilized egg develops into a
hollow, two-layered ball of cells. The outer layer directly contacts and invades the womb
lining, while the inner cell mass develops into the embryo, membranes and blood
vessels. In particular, outer layer cells distend and weaken the walls of spiral arteries,

such that maternal blood flows unhindered into the space surrounding fetal membrane
outgrowths. This crucial modification is diminished in pre-eclampsia and the
characteristic blood pressure rise is apparently a mechanism, probably triggered by the
fetus, to augment blood flow through the placenta. A thoughtful 1993 review of
mother:fetus conflicts during pregnancy by David Haig suggested that pre-eclampsia
may amount to an attempt by the fetus to counter insufficiency of the placenta and
increase nutrient supply.
Scarce knowledge about the condition in other placental mammals hampers
ourunderstanding of the causes of pre-eclampsia in women. Isolated cases have been
reported for non-human primates: five great apes and four Old World monkeys.
However, a 1979 paper by Amos Palmer and colleagues reported pre-eclampsia,
characterized by limb swelling, raised blood pressure and excess urinary protein in six
out of 98 pregnancies in a laboratory breeding colony of patas monkeys. As in women,
the incidence was also higher with first-time pregnancies. Careful monitoring is needed
to recognize symptoms, so the frequency of pre-eclampsia in other primates has
probably been underestimated. But perhaps the patas monkey provides an unusual
example of late-onset pre-eclampsia among non-human primates. Either way, the lack
of any follow-up is regrettable.
Pre-eclampsia and maternal immunity
Proteins of paternal origin in the fetus and placenta challenge a pregnant woman's
immune system. Significantly, pre-eclampsia is clearly a disease of first pregnancy,
being at least twice as frequent with first-time mothers as in subsequent pregnancies.
This suggests that a womans immune system slowly adapts to proteins from a specific
male partner.

Incidence of pre-eclampsia according to type of pregnancy

Source: Adapted from a figure provided by MacGillivray (1958)

Supporting this are several reports that high blood pressure in pregnancy becomes less
frequent with increasing duration of a couples sexual co-habitation. Pierre-Yves
Robillard, who co-authored a landmark 1994 paper based on prospective study of over
1,000 pregnant women in Guadeloupe, has championed this interpretation. Cases of
raised blood pressure in pregnancy were examined in relation to the mothers period of
cohabitation with the father before conception. High blood pressure occurred in 12% of
first-time mothers but only 5% of mothers with previous pregnancies with the same
father. Strikingly, a highly significant decrease in occurrence of high blood pressure
accompanied increasing duration of sexual cohabitation before conception, falling from
a staggering 40% at 4 months or less to around 5% beyond a year. But the incidence
was 24% in women who conceived with a new partner after previous births. Robillard
and colleagues concluded that high blood pressure in pregnancy may be more a
problem of first fatherhood than of first pregnancy.

Incidence of pre-eclampsia according to period of sexual cohabitation.

Source: Adapted from a figure provided by Robillard et al. (2014)

There was no real follow-up until 2002. But then Rolv Skjaerven and colleagues
reported that the risk of pre-eclampsia may depend on the interval between pregnancies
rather than on length of cohabitation. A longer gap between births is likely to follow any
partner change. Analysis of data for almost 1,500,000 pregnancies confirmed previous
findings: pre-eclampsia occurred in almost 4% percent of first pregnancies, but less
than 2% of second and third pregnancies. But it also revealed that the risk of preeclampsia rises with time elapsed since the previous birth, regardless of partner
change. However, long birth intervals may be linked to less frequent coitus, so
sexual priming could still be a key factor.
Evidence for sexual priming
In 1983, Jillian Need and colleagues reported an analysis of almost 600 cases of
artificial insemination with semen from unfamiliar donors. The overall incidence of preeclampsia was two to three times higher than in the general population. And no

difference was seen between first-time and subsequent pregnancies. Reinforcing the
interpretation that a reaction to unfamiliar proteins is involved, similar findings have
been reported for infertility treatment using egg donation. Women who become
pregnant with donated eggs are at greater risk of high blood pressure, especially preeclampsia. At a conference held in 2014, Hlne Letur-Koenirsch and colleagues
reported results from almost 600 pregnancies including over 200 with egg donation.
Compared to controls, the risk of high blood pressure was more than three times
greater in pregnancies with donated eggs, and previous pregnancy had no significant
effect.
Moreover, a 2003 paper by Jon Einarsson and colleagues examined the relationship
between frequency of pre-eclampsia and previous exposure to a partners semen. Over
a hundred women with pre-eclampsia were compared with twice as many matched
controls with normal blood pressure. For first-time pregnancies, the risk of preeclampsia was significantly higher for women using semen-blocking contraception who
had cohabited with their sexual partners less than 4 months than for women who
cohabited for over a year before conception.
The relationship between contraceptives and pre-eclampsia is interesting in itself. In a
1977 paper Jean-Jacques Marti and Uli Herrman examined the incidence of preeclampsia in women using oral contraceptives. They found that episodes of unprotected
sexual intercourse for women in a control group were three times more common than in
women with pre-eclampsia, supporting the interpretation that contact with semen has a
protective effect. In 1989, Hillary Klonoff-Cohen and colleagues reported on a casecontrol study designed to test whether barrier methods that block exposure to semen
are associated with an increased risk of pre-eclampsia during subsequent pregnancy.
Over a hundred women who experienced pre-eclampsia during first-time pregnancies
were compared with as many pregnant women without raised blood pressure. The risk
of pre-eclampsia was more than twice as high in users of barrier contraception and
increased with decreasing exposure to semen.
Yet more evidence for a priming effect of semen came from a 2000 paper by Carin
Koelman and colleagues. They discovered that a low incidence of pre-eclampsia was

associated with oral sex, especially if semen was swallowed. They proposed a crucial
rle for induction of maternal tolerance to paternal antigens that they identified in
seminal plasma.
So a woman may need exposure to semen from a particular male partner for several
months to develop adequate immunological tolerance of the fetus in her womb. Without
such priming, the mothers immune system reacts negatively to the fetus and
compromises development of blood vessels in the placenta. The resulting increase in
blood pressure is a counter-measure that boosts maternal bloodflow to offset
deficiencies of the spiral arteries. This throws entirely new light on the significance of
lengthy courtship and strong pair bonding in humans.
References
Einarsson, J.I., Sangi-Haghpeykar, H. & Gardner, M.O. (2003) Sperm exposure and
development of pre-eclampsia. American Journal of Obstetrics & Gynecology 188:12411243.
Haig, D. (1993) Genetic conflicts in human pregnancy. Quarterly Review of
Biology68:495-532.
Klonoff-Cohen, H.S., Savitz, D.A., Cefalo, R.C. & McCann, M.F. (1989) An
epidemiologic study of contraception and preeclampsia. Journal of the American
Medical Association262:3143-3147.
Koelman, C.A., Coumans, A.B., Nijman, H.W., Doxiadis, I.I. & Dekker, G.A. (2000)
Correlation between oral sex and a low incidence of pre-eclampsia: A role for soluble
HLA in seminal plasma. Journal of Reproductive Immunology 46:155-166.
Letur-Koenirsch, H., Peigne, M., Ohl, J., Cedrin, I., d'Argent, E.M., Scheffler, F.,
Gzregorczyk-Martin, V. & de Mouzon, J. (2014) Pregnancies issued from egg donation
are associated to a higher risk of hypertensive pathologies then control ART

pregnancies. Results of a large comparative cohort study. Human Reproduction 29,

Supplement 1:68-69.
Marti, J.-J. & Herrmann, U. (1977) Immunogenetics: A new etiologic concept of
"essential" EPH gestosis, with special consideration of the primigravida
patient. American Journal of Obstetrics & Gynecology 128:489-493.
MacGillivray, I. (1958) Some observations on the incidence of preeclampsia. Journal of
Obstetrics & Gynaecology of the British Empire 65:536-539.
Need, J.A., Bell, B., Meffin, E. & Jones, W.R. (1983) Pre-eclampsia in pregnancies from
donor inseminations. Journal of Reproductive Immunology 5:329-338.
Palmer, A.E., London, W.T., Sly, D.L. & Rice, J.M. (1979) Spontaneous preeclamptic
toxemia of pregnancy in the patas monkey (Erythrocebus patas). Laboratory Animal
Science 29:102-106.
Robillard, P.-Y., Hulsey, T.C., Perianin, J., Janky, E., Miri, E.H. & Papiernik, E. (1994)
Association of pregnancy-induced hypertension with duration of sexual cohabitation
before conception. Lancet 344:973-975.
Skjaerven, R., Wilcox, A.J. & Lie, R.T. (2002) The interval between pregnancies and the
risk of preeclampsia. New England Journal of Medicine 346:33-38.
Yuan, H.T., Haig, D. & Ananth Karumanchi, S. (2005) Angiogenic factors in the
pathogenesis of preeclampsia. Current Topics in Developmental Biology 71:297-312.