Pre-eclampsia and partial uterine denervation.

Pre-eclampsia is characterised by a maternal syndrome of hypertension and proteinuria, that is frequently associated with reduced fetal growth. The characteristic histopathological observation in the placental bed is narrowing and atherosis of the distal branches of the uterine arteries at, and around, the deciduo-myometrial interface. In the maternal kidneys there is swelling of the glomerular capillaries and mesangium with some inclusions in the basement membrane ("glomeruloendotheliosis") and evidence of vasoconstriction in many other organs. Untreated maternal hypertension leads to convulsions (eclampsia) which may result in maternal and fetal death. The nerve plexus at the endometrial(decidual)--myometrial interface was first reported in 1959 though has received little attention in the intervening years. It appears to play an important role in maintaining the separation of two tissues with intrinsic proliferative potential (endometrium and myometrium). The present hypothesis proposes that damage to the nerve plexus at the endometrial-myometrial interface causes impaired control of a third proliferative tissue (invading trophoblast) resulting in the characteristic histological changes. Growth factors produced by nerves and blood vessels may contribute to the process of normal placentation e.g. nerve growth factor, vascular endothelial growth factor, etc. and these processes may be compromised in areas of denervation. Neural connections between the uterine and renal innervations (L1, 2) result in renal vasoconstriction and widespread systemic maternal vasoconstriction in an attempt to provide increased blood flow for the uteroplacental circulation (maternal hypertension, small-for-gestational age fetus). Loss of these neural connections through the same process of partial uterine denervation may cause reduced fetal growth without the maternal circulatory changes of pre-eclampsia (maternal normotension, small-for-gestational age, fetus). Variations in maternal circulatory compliance alter the "phenotype" of the condition such that prior maternal hypertension may cause pre-eclampsia through intrarenal mechanisms without significant fetal growth restriction. Increases in circulatory compliance in multiparity prevent the typical features of the condition, or, if they are expressed then they present in a different sequence with haematological and hepatic consequences presenting before the renal manifestations (HELLP syndrome, haemolysis, elevated liver enzymes, low platelets).