The influence of the intrauterine environment on human placental development

Centre for Trophoblast Research, University of Cambridge, Cambridge, UK.
The International journal of developmental biology (Impact Factor: 2.57). 09/2009; 54(2-3):303-12. DOI: 10.1387/ijdb.082764gb
Source: PubMed

ABSTRACT Development of the human placenta is modulated heavily by the intrauterine environment. During the first trimester, development takes place in a low oxygen environment supported by histiotrophic nutrition from the endometrial glands. Consequently, the rate of growth of the chorionic sac is almost invariable across this period, and is remarkably uniform between individuals. Towards the end of the first trimester the intrauterine environment undergoes radical transformation in association with onset of the maternal arterial circulation and the switch to haemotrophic nutrition. The accompanying rise in intraplacental oxygen concentration poses a major challenge to placental tissues, and extensive villous remodelling takes place at this time. Later in pregnancy a wide variety of stressors are capable of affecting placental growth, but in the human, the most common are nutrient deprivation and vascular compromise. The latter is usually secondary to deficient trophoblast invasion and can induce placental oxidative stress. Closely linked to oxidative stress is endoplasmic reticulum stress, and we recently provided the first evidence that the latter plays a major role in the pathophysiology of intrauterine growth restriction. The endoplasmic reticulum is a key regulator of protein synthesis, exerting its effects through the unfolded protein response. Consequently, we observed multiple blocks to translation initiation and elongation in growth restricted placentas. Nutrient deprivation also modulates protein synthesis through the mTOR pathway, and we demonstrated interactions between this pathway and endoplasmic reticulum stress. Protein synthesis inhibition therefore appears to be a common mechanism for regulating placental development under different adverse conditions.

Download full-text


Available from: David Stephen Charnock-Jones, Jul 20, 2015
  • Source
    • "By contrast, excessive ROS production results in oxidatively stressful conditions, inflammation, circulatory derangement, and placental bed cell apoptosis or necrosis. These events may occur transiently during labour in a fashion consistent with ischaemiareperfusion injury [26]; when lasting longer, or throughout the pregnancy, they may result in placental function impairment [27] [28] and serious pregnancy complications [24] [28]. Despite the likelihood of the process of ROS production, the identity and contribution of the redox players involved have remained unknown. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Blood flow assessment employing Doppler techniques is a useful procedure in pregnancy evaluation, as it may predict pregnancy disorders coursing with increased uterine vascular impedance, as pre-eclampsia. While the local causes are unknown, emphasis has been put on reactive oxygen species (ROS) excessive production. As NADPH oxidase (NOX) is a ROS generator, it is hypothesized that combining Doppler assessment with NOX activity might provide useful knowledge on placental bed disorders underlying mechanisms. A prospective longitudinal study was performed in 19 normal course, singleton pregnancies. Fetal aortic isthmus (AoI) and maternal uterine arteries (UtA) pulsatility index (PI) were recorded at two time points: 20-22 and 40-41 weeks, just before elective Cesarean section. In addition, placenta and placental bed biopsies were performed immediately after fetal extraction. NOX activity was evaluated using a dihydroethidium-based fluorescence method and associations to PI values were studied with Spearman correlations. A clustering of pregnancies coursing with higher and lower PI values was shown, which correlated strongly with placental bed NOX activity, but less consistently with placental tissue. The study provides evidence favoring that placental bed NOX activity parallels UtA PI enhancement and suggests that an excess in oxidation underlies the development of pregnancy disorders coursing with enhanced UtA impedance. Copyright © 2015 The Authors. Published by Elsevier B.V. All rights reserved.
    04/2015; 5:114-123. DOI:10.1016/j.redox.2015.04.007
  • Source
    • "Placentation is an oxygen sensitive process. The events that occur from the time of implantation to maternal perfusion of the placenta are influenced and directed by site-specific oxygen tensions [22]. An oxygen gradient exists between the placenta and endometrium during the first trimester. "
    [Show abstract] [Hide abstract]
    ABSTRACT: A tenet of contemporary obstetrics is that events that compromise placentation increase the risk of complications of pregnancy and contribute to poor pregnancy outcome. In particular, conditions that affect the invasion of placental cells and remodeling of uterine spiral arteries compromise placental function and the subsequent development of the fetus. Extravillous trophoblast cells (EVTs) proliferate and migrate from the cytotrophoblast in the anchoring villi of the placenta and invade the maternal decidua and myometrium. These cells are localised with uterine uterine spiral arteries and are thought to induce vascular remodeling. A newly identified pathway by which EVTs may regulate vascular remodeling within the uterus is via the release of exosomes. Trophoblast cells release exosomes that mediate aspects of cell-to-cell communication. The aim of this brief commentary is to review the putative role of exosomes released from extravillous trophoblast cells in uterine spiral artery remodeling and, in particular, their role in the aetiology of preeclampsia. Placental exosomes may engage in local cell-to-cell communication between the cell constituents of the placenta and contiguous maternal tissues and/or distal interactions, involving the release of placental exosomes into biological fluids and their transport to a remote site of action.
    BioMed Research International 09/2014; 2014:693157. DOI:10.1155/2014/693157
  • Source
    • "(C) Placental villous structure. at the end of the first trimester (Fig. 1B; Burton et al. 2010), and interstitial EVTs (Fig. 1B), the role of which is unclear. Spiral artery remodelling begins in the absence of any invasive EVTs whereby uNK cells disrupt the vascular smooth muscle surrounding the arteries priming the arteries for EVT colonization (Harris 2011). "
    [Show abstract] [Hide abstract]
    ABSTRACT: The establishment of a successful pregnancy requires the implantation of a competent blastocyst into a 'receptive' endometrium, facilitating the formation of a functional placenta. Inadequate or inappropriate implantation and placentation is a major reason for infertility and is thought to lead to first trimester miscarriage, placental insufficiency and other obstetric complications. Blastocyst-endometrial interactions are critical for implantation and placental formation.The Notch signalling family is a receptor-ligand family that regulates cellular processes as diverse as proliferation, apoptosis, differentiation, invasion and adhesion. Notch signalling is achieved via cell-cell interaction, thus, via Notch, cells can have direct effects on the fate of their neighbours. Recently, a number of studies have identified Notch receptors and ligands in the endometrium, blastocyst and placenta. This review collates current knowledge of this large receptor-ligand family and explores the role of Notch signalling during implantation and placentation, drawing on information from both human and animal studies. Overall, the evidence suggests that Notch signalling is a critical component of fetal-maternal communication during implantation and placentation and that abnormal Notch expression is associated with impaired placentation and preeclampsia.
    Reproduction 12/2013; DOI:10.1530/REP-13-0474
Show more