161. Placental development, blood flow and pre-eclampsia; A role for the endometrium?

Abstract

Placental stress, induced by maternal malperfusion, is believed to be at the epicentre of the pathophysiology of pre-eclampsia, at least for the early-onset sub-type. Deficient remodelling of the spiral arteries has been well documented in the placental bed, with the degree correlating with time of onset of the syndrome. Despite this progress, the cause for the deficiency is still not known. Impaired invasion by the extravillous trophoblast cells essential to the remodelling process has been implicated, as have aberrant interactions between these cells and those of the maternal immune system present in the decidua. Another possibility is that early development of the placenta post-implantation is abnormal, resulting in an impoverished supply of extravillous trophoblast cells. Although this hypothesis has received little attention to date, recent transcriptional analyses have revealed abnormalities in decidualisation in women prior to, and after, pre-eclampsia. Initial growth of the placenta is stimulated by histotroph from the endometrial glands, which contains numerous mitogenic growth factors as well as glucose, lipids and other nutrients. The secretory activity of the glands increases in early pregnancy in response to lactogenic hormones produced by the placenta. However, details of the signalling pathways involved are unknown due to the inaccessibility of the tissues concerned. The recent derivation of endometrial organoids now allows these pathways to be dissected, and prolactin is emerging as a strong stimulant of glandular secretion. Prolactin is secreted by decidual cells, and so may link the transcriptomic data with the supply of extravillous trophoblast cells and deficient arterial remodelling. If the hypothesis were proved correct, the translational impact would be to emphasise the importance of ensuring optimal endometrial function prior to conception. This would have the great advantage of preventing the pre-eclampsia and other placental-related complications at their outset, rather than trying to treat these disorders once established.