Whatever the factors involved in controlling the materno–placental interaction, the aim is to enable implantation, placentation and the subsequent progressive transformation of the maternal vasoreactive spiral arteries into flaccid, distended utero–placental arteries needed to supply the developing fetus and its placenta with an increasing amount of maternal blood in later pregnancy.
The form of placentation varies widely across mammalian species, but as yet no satisfactory explanation of the evolutionary driving forces has been provided. In most species, there is no invasion of the maternal endometrium, and the conceptus remains within the uterine lumen throughout gestation. The extraembryonic membranes are simply apposed to the uterine epithelium, establishing a relationship classified as epitheliochorial. In others, particularly the carnivores, there is limited erosion of the maternal tissues so that the trophoblast is apposed to the endothelium of the maternal vessels, forming an endotheliochorial placenta. In the past, it has been assumed that the increasing depth of invasion was evidence of evolutionary progression, with the haemochorial situation representing the most advanced state. By providing trophoblast with direct access to the maternal blood, it was thought that the haemochorial situation permitted more efficient transfer of nutrients, including O2
, which allowed for greater development of the brain (Martin, 2003
). However, dolphins which have epitheliochorial placentae produce large-brained fetuses second only in size to human fetuses (Martin, 2003
). More recently, cladistic analyses have suggested that in fact the endotheliochorial relationship is the most primitive form and that the epitheliochorial and haemochorial relationships are parallel advancements (Vogel, 2005
Despite the potential advantages for materno–fetal transfer it provides, the haemochorial relationship undoubtedly has a number of potential drawbacks. Firstly, there is a risk that the fetal capillaries within the placental villi may be compressed by the higher pressure inherent in the maternal circulation (Karimu and Burton, 1994
). It is therefore essential that the pressure in the intervillous space is kept lower than fetal venous pressure, requiring a pressure drop from mean maternal arterial pressure to approximately 10 mmHg. Trophoblast invasion and conversion of the uterine arteries in haemochorial placentation is more likely to be important in this respect and in ensuring constancy of flow, rather than simply increasing uterine artery blood flow. The latter occurs in all species irrespective of trophoblast invasion and is an endocrine-mediated effect. As we have seen, however, the phenomenon of trophoblast invasion brings with it another set of immunological problems, and these have to be balanced evolutionarily against the benefits of the haemochorial relationship for nutrient transfer. The precise details of the latter remain obscure at present.
Secondly, in the haemochorial state, once maternal blood has been released into the placenta, there is little control over the direction or rate of flow, save for the uterine aterio–venous pressure differential. In contrast, retaining the maternal blood within a capillary network in the epitheliochorial and endotheliochorial situations allows maternal and fetal perfusion of the placenta to be matched more closely, and hence major fluctuations in oxygenation are likely to be less common. Finally, the haemochorial situation allows the trophoblast uniquely intimate and extensive access to the maternal circulation. Inflammatory cytokines, soluble receptors, fetal DNA and trophoblastic debris can all be released with ease directly into the maternal blood and hence disseminated widely throughout the mother's body. This is in stark contrast to the situation in, for example, an epitheliochorial placenta where trophoblast microparticles would have to cross the uterine epithelium, its basement membrane, any intervening stromal tissue and finally the capillary endothelium in order to gain similar access.
Miscarriages are the most common human pregnancy disorder with 50% of all conceptions lost before or around implantation and another 20% lost between implantation and completion of the first trimester (Edmonds et al., 1982
; Norwitz et al., 2001
). The difference in miscarriage rates between humans and other mammals including primates is linked to a difference in chromosomal abnormalities which occur at a rate of more than 50% in humans compared with less than 5% in rats, rabbits and hamsters (Hassold, 1986
). The high rate of chromosomal abnormalities in humans could be because of the longer reproductive spans of humans which would lead to an accumulation of chromosomal errors not observed in short-lived mammalian species (Hassold, 1986
). Indeed, the incidence of chromosomal abnormalities in the human conceptus increases with maternal and paternal age. Other known causes of miscarriages such as infections have been described in both humans and other mammals but account for only a small percentage of early pregnancy losses. Modern lifestyle and in particular delayed childbirth, maternal smoking and hypercaloric diets leading to diabetes have most certainly increased the incidence of miscarriage in the general population worldwide. The high incidence of miscarriages in the human could also reflect the separation of coitus from ovulation, with the risk of post-ovulatory aged oocytes and post-ejaculatory aged sperm throwing up genetic abnormalities. Overall, all causes of miscarriages lead to major trophoblastic dysfunction with major disturbances of the early phases of the placentation process.
Threatened miscarriages are to be considered separately from other forms of miscarriages as they result from a focal bleed in the periphery of the developing placenta. This bleed occurs at the time of the formation of the membranes and can lead to a complete miscarriage if the hematoma extends into the definitive placenta (Johns et al., 2003
). Very early (in the first 8 weeks) vaginal bleeding is not associated with subsequent pregnancy complications, whereas the formation of an intrauterine hematoma at 13–14 weeks increases the risk of pre-eclampsia (Harville et al., 2003
). The presence of a haematoma may also be associated with a chronic inflammatory reaction in the decidua resulting in persistent myometrial activity and expulsion of the pregnancy or progressive cellular dysfunction and/or damage to cellular layers of the membranes leading to pre-term rupture and delivery (Silver et al., 2005
). Whatever the evolutionary benefits of haemochorial placentation, it appears to be a key factor in the high rate of this very common complication of human gestation, affecting between 10 and 15% of ongoing pregnancies.
Human physiological adjustments to pregnancy resemble those of our primate relatives but differ in several key aspects; most notably, humans have earlier, deeper and more extensive placentation. The human placenta is also larger relative to the uterine size (Martin, 2003
). It has been suggested that the human placenta is designed as a means for overcoming the mechanical constraints and consequent reduction in cardiac output because of bipedal posture (Rockwell et al., 2003
). The genetic conflict hypothesis predicts that maternal blood pressure is determined by the balance between fetal and placental paternally-inherited factors increasing blood pressure and maternal factors decreasing blood pressure (Haig, 1993
). The paternal contribution tends to favour invasiveness of the placenta and thus increases feto–placental capture of maternal resources, whereas the maternal contribution tends to favour a lesser degree of placental response and to promote fetal brain development (Keverne et al., 1996
). The placental response invasion may be a secondary strategy to increase non-placental resistance when the utero–placental blood supply is inadequate, but if so, it would appear to be a highly risky one.