Decidual cytokines and pregnancy complications: focus on spontaneous miscarriage

Abstract

The establishment of pregnancy requires the co-ordinated implantation of the embryo into the receptive decidua, placentation, trophoblast invasion of the maternal decidua and myometrium in addition to remodelling of the uterine spiral arteries. Failure of any of these steps can lead to a range of pregnancy complications, including miscarriage, pre-eclampsia, fetal growth restriction, placenta accreta and pre-term birth. Cytokines are small multifunctional proteins often derived from leucocytes and have primarily been described through their immunomodulatory actions. The maternal-fetal interface is considered to be immunosuppressed to allow development of the semi-allogeneic placental fetal unit. However, cytokine profiles of the decidua and different decidual cell types suggest that the in vivo situation might be more complex. Data suggest that decidual-derived cytokines not only play roles in immunosuppression, but also in other aspects of the establishment of pregnancy, including the regulation of trophoblast invasion and spiral artery remodelling. This review focuses on the potential role of decidua-derived cytokines in the aetiology of unexplained spontaneous miscarriage. (C) 2015 Elsevier Ireland Ltd. All rights reserved

The role of neutrophil activation in determining the outcome of pregnancy and modulation by hormones and/or cytokines

“…While an essential function of these hormones is to regulate maternal metabolism in order to promote fetal growth or alter the ability of fetal trophoblast cells to invade maternal tissue, several of these factors have been shown to possess additional immune modulatory capacity [25,26]. While an essential function of these hormones is to regulate maternal metabolism in order to promote fetal growth or alter the ability of fetal trophoblast cells to invade maternal tissue, several of these factors have been shown to possess additional immune modulatory capacity [25,26].…”

“…A vast array of peptide hormones, many of which are produced by the placenta, contribute to the completion of a successful pregnancy, including human placental lactogen (hPL), calcitonin, activins and inhibins, placenta growth factor (PGF) or leptin. While an essential function of these hormones is to regulate maternal metabolism in order to promote fetal growth or alter the ability of fetal trophoblast cells to invade maternal tissue, several of these factors have been shown to possess additional immune modulatory capacity [25,26]. Of particular interest in this discourse is human chorionic gonadotrophin (hCG) and vasoactive intestinal peptide (VIP) [27].…”

“…© 2019 British Society for Immunology, Clinical and Experimental Immunology, 198:[24][25][26][27][28][29][30][31][32][33][34][35][36] …”

Alterted SLIT2/ROBO1 signalling is linked to impaired placentation of missed and threatened miscarriage in early pregnancy

“…Although it has been reported clinically that genetic abnormalities account for approximately 50% of early spontaneous miscarriages, accumulating evidence indicates that defective placental angiogenesis is involved in the pathogenesis of early pregnancy failure . Vaginal bleeding during the first trimester originates commonly from the spiral arteries at the fetal–maternal interface, and two‐thirds of early pregnancy failures present with reduced trophoblast invasion of the spiral arteries . However, little is known about the precise mechanism underlying placental angiogenesis and its contribution to the aetiology of spontaneous miscarriage.…”

“…4 Vaginal bleeding during the first trimester originates commonly from the spiral arteries at the fetal-maternal interface, and two-thirds of early pregnancy failures present with reduced trophoblast invasion of the spiral arteries. 5 However, little is known about the precise mechanism underlying placental angiogenesis and its contribution to the aetiology of spontaneous miscarriage.…”