Fetal-Maternal Conflict, Trophoblast Invasion, Preeclampsia, and the Red Queen

Abstract

The much publicized conflict hypothesis for understanding fetal-maternal interaction during pregnancy often invokes a 'battle' metaphor, rather than a well orchestrated interplay occurring as a series of well controlled moves and counter-moves as happens in a game of chess. Such stepwise interaction is particularly obvious in the spiral artery remodelling process, and it would be interesting to trace the history of the successive steps in histological adaptation throughout primate phylogeny. The restricted invasion observed in a few species on a 'lower' evolutionary scale suggests a tendency of progressive deeper invasion during primate evolution. Unfortunately, our knowledge of invasive processes in the placental bed in nonhuman primates is highly inadequate. A paradigm underscoring the stepwise interaction between mother and fetus may be provided by the Red Queen hypothesis, which is a useful model to explain co-evolutionary processes between different species. The apparent association between preeclampsia and restricted endovascular trophoblast invasion, combined with the absence of the disease in primate species showing shallow invasion, suggests that preeclampsia may result from a failure in one or more interactive steps necessary for deeper invasion. Evidence for a genetic component invokes the puzzling question as to why "preeclampsia genes" are not eliminated from human populations. As in other fields of medicine, a proper understanding of Darwinian selection processes may throw some light on the causes of preeclampsia.

The role of invasive trophoblast in implantation and placentation of primates

“…The evolution of deep trophoblast invasion and modulation of the maternal immune response seems to have come at a price [5]. Firstly, there is a high incidence of postpartum haemorrhage in human pregnancy, with little evidence for excessive bleeding in other primates [71].…”

“…In human pregnancy, trophoblast invasion of the uterine spiral arteries leads to extensive remodelling of the vessel wall. Because shallow implantation has been linked to several obstetrical syndromes [5], there has lately been a focus on arterial remodelling in baboons and macaques; early workers [6] had paid scant attention to the placental bed. Recently, these studies have been extended to the great apes.…”

The Interrelationship of Complement-Activation Fragments and Angiogenesis-related Factors in Early Pregnancy and Their Association With Preeclampsia

“…The reason for excluding the cases of gestational hypertension was to avoid misclassification of the outcome, because of the uncertainty in whether gestational hypertension is a separate entity from pre-eclampsia or a mild version of pre-eclampsia. 20 An a priori decision was made to concentrate the analysis on women who had blood taken between 10 and 15 weeks of gestation to: (a) reflect the major time of uteroplacental vascular remodelling, 15 and (b) reduce the potential confounding effect of gestational age at blood draw. For this reason, women enrolled at a gestational age of <10 weeks or >15 weeks of gestation (n = 375) were excluded from the analysis.…”

“…The complement system has thus a key role in early pregnancy, 14 a time of intense tissue and vascular remodelling. 15 In brief, there are three complement pathways: the classical, lectin and alternative pathways. 10,16,17 These pathways converge to generate enzymes called C3 convertases, which cleave the third component of the complement system into C3b and C3a.…”

A review of inter- and intraspecific variation in the eutherian placenta

“…During a normal human pregnancy, the trophoblast invades into the maternal myometrium and extracts nutrients from maternal blood [104]. Conflict arises because while the mother wants to limit trophoblast invasion, the placenta invades deeply thereby extracting more nutrients [104,105]. Cooperation is necessary to balance invasion.…”