Stephen J Renaud

Stephen J Renaud
The University of Western Ontario | UWO · Department of Anatomy and Cell Biology

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62
Publications
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1,347
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Publications

Publications (62)
Article
Full-text available
In humans, cell fusion is restricted to only a few cell types under normal conditions. In the placenta, cell fusion is a critical process for generating syncytiotrophoblast: the giant multinucleated trophoblast lineage containing billions of nuclei within an interconnected cytoplasm that forms the primary interface separating maternal blood from fe...
Article
Full-text available
Maternal infections during pregnancy are linked with an increased risk for disorders like Autism Spectrum Disorder and schizophrenia in the offspring. Although precise mechanisms are still unclear, clinical and preclinical evidence suggests a strong role for maternal immune activation (MIA) in the neurodevelopmental disruptions caused by maternal i...
Chapter
The placenta is a multifunctional organ that develops during pregnancy and is critical for supporting fetal growth and viability. Major functions of the placenta include facilitating nutrient and gas exchange between maternal and fetal circulations, immunological protection, endocrinological support, and modification of the uterine vasculature. The...
Article
Decorin, a small leucine-rich proteoglycan produced by decidual cells restrains trophoblast differentiation, migration and invasiveness of extra-villous trophoblast cells. Decidual overproduction of decorin is associated with preeclampsia, and elevated decorin levels in maternal plasma are a predictive biomarker of preeclampsia. Furthermore, decori...
Article
Iron deficiency occurs when iron demands chronically exceed intake, and is prevalent in pregnant women. Iron deficiency during pregnancy poses major risks for the baby, including fetal growth restriction and long-term health complications. The placenta serves as the interface between a pregnant mother and her baby, and ensures adequate nutrient pro...
Article
Full-text available
Post-traumatic osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is...
Article
Full-text available
Proper development of the placenta is vital for pregnancy success. The placenta regulates exchange of nutrients and gases between maternal and fetal blood and produces hormones essential to maintain pregnancy. The placental cell lineage primarily responsible for performing these functions is a multinucleated entity called syncytiotrophoblast. Syncy...
Preprint
Full-text available
Post-traumatic Osteoarthritis (PTOA) is a degenerative joint disease, leading to articular cartilage breakdown, osteophyte formation, and synovitis, caused by an initial joint trauma. Pro-inflammatory cytokines increase catabolic activity and may perpetuate inflammation following joint trauma. Interleukin-15 (IL-15), a pro-inflammatory cytokine, is...
Article
Full-text available
Background: Both high and low placental weights are associated with adverse pregnancy outcomes. Maternal hemoglobin levels can influence placental weight, but the evidence is conflicting. Since maternal hemoglobin does not invariably correlate with fetal/neonatal blood hemoglobin levels, we sought to determine whether cord blood hemoglobin or mate...
Article
A critical component of early human placental development includes migration of extravillous trophoblasts (EVTs) into the decidua. EVTs migrate toward and displace vascular smooth muscle cells (SMCs) surrounding several uterine structures, including spiral arteries. Shallow trophoblast invasion features in several pregnancy complications including...
Article
Decidualization involves the proliferation and differentiation of fibroblast-like endometrial stromal cells into epithelioid-shaped and secretory 'decidual' cells in response to steroid hormones. Human decidual cells produce insulin-like growth factor-binding protein-1 and prolactin (PRL), two well-recognized markers of decidual cell maturation and...
Article
Full-text available
Iron is an essential mineral that participates in oxygen transport, DNA synthesis and repair, and as a cofactor for various cellular processes. Iron deficiency is the most common nutritional deficiency worldwide. Due to blood volume expansion and demands from the fetal-placental unit, pregnant women are one of the populations most at risk of develo...
Article
Full-text available
Maternal immune activation (MIA) caused by exposure to pathogens or inflammation during critical periods of neurodevelopment is a major risk factor for behavioral deficits and psychiatric illness in offspring. A spectrum of behavioral abnormalities can be recapitulated in rodents by inducing MIA using the viral mimetic, PolyI:C. Many studies have f...
Preprint
Full-text available
A critical component of early human placental development includes migration of extravillous trophoblasts (EVTs) into the decidua. EVTs migrate toward, and displace vascular smooth muscle cells (SMCs) surrounding several uterine structures, including spiral arteries. Shallow trophoblast invasion features in several pregnancy complications including...
Article
Full-text available
Cell fusion occurs when several cells combine to form a multinuclear aggregate (syncytium). In human placenta, a syncytialized trophoblast (syncytiotrophoblast) layer forms the primary interface between maternal and fetal tissue, facilitates nutrient and gas exchange, and produces hormones vital for pregnancy. Syncytiotrophoblast development occurs...
Article
Full-text available
Trophoblasts are the first cell type to be specified during embryogenesis, and they are essential for placental morphogenesis and function. Trophoblast stem (TS) cells are the progenitor cells for all trophoblast lineages; control of TS cell differentiation into distinct trophoblast subtypes is not well understood. Mice lacking the transcription fa...
Article
Full-text available
Many viruses are detrimental to pregnancy and negatively affect fetal growth and development. What is not well understood is how virus-induced inflammation impacts fetal-placental growth and developmental trajectories, particularly when inflammation occurs in early pregnancy during nascent placental and embryo development. To address this issue, we...
Article
Full-text available
Abstract Extravillous trophoblast (EVT) invasion is an essential component of human placentation. Poor EVT invasion is associated with obstetrical complications including preeclampsia. Integration of cues from the extracellular environment is required for directional EVT invasion, but how EVTs coordinate responses to these cues is not well understo...
Chapter
The placenta is a multifunctional organ that develops during pregnancy and is critical for supporting fetal growth and viability. Major functions of the placenta include facilitating nutrient and gas exchange between maternal and fetal circulations, providing immunological protection and endocrinological support, and modifying the uterine vasculatu...
Chapter
Full-text available
The placenta is a transient organ that plays a critical role in sustaining pregnancy and supporting fetal growth and nutrition. The placental epithelium is comprised of trophoblast cells. Trophoblast cells are the first cell type to differentiate during embryogenesis and ultimately diversify into a heterogeneous population of cells specializing in...
Article
Natural killer (NK) cells are the most prevalent leukocyte population in the uterus during early pregnancy. Natural killer cells contribute to uterine vascular (spiral artery) remodeling in preparation for the increased demand on these vessels later in pregnancy. A second wave of spiral artery modification is directed by invasive trophoblast cells....
Article
Full-text available
The hemochorial placenta develops from the coordinated multilineage differentiation of trophoblast stem (TS) cells. An invasive trophoblast cell lineage remodels uterine spiral arteries, facilitating nutrient flow, failure of which is associated with pathological conditions such as preeclampsia, intrauterine growth restriction, and preterm birth. H...
Article
Epithelial barrier integrity is dependent on progenitor cells that either divide to replenish themselves or differentiate into a specialized epithelium. This paradigm exists in human placenta, where cytotrophoblast cells either propagate or undergo a unique differentiation program: fusion into an overlying syncytiotrophoblast. Syncytiotrophoblast i...
Article
Implantation of the embryo into the uterus triggers the initiation of hemochorial placentation. The hemochorial placenta facilitates the acquisition of maternal resources required for embryo/fetal growth. Uterine spiral arteries form the nutrient supply line for the placenta and fetus. This vascular conduit undergoes gestation stage-specific remode...
Article
Implantation of the embryo into the uterus triggers the initiation of hemochorial placentation. The hemochorial placenta facilitates the acquisition of maternal resources required for embryo/fetal growth. Uterine spiral arteries form the nutrient supply line for the placenta and fetus. This vascular conduit undergoes gestation stage-specific remode...
Article
Full-text available
Extravillous trophoblast invasion is a fundamental component of human placentation. Invading trophoblast cells promote blood flow to the conceptus by actively remodeling the uterine vasculature. The extent of trophoblast invasion is tightly regulated; aberrant invasion is linked with several obstetrical complications. However, the transcriptional n...
Article
Trophoblast cells are phenotypically diverse epithelial cells that comprise the principal structural and functional components of the placenta. All trophoblast cells differentiate from common progenitor cells. However, studying human trophoblast differentiation has been hampered by an inability to stably culture human progenitor trophoblast cells....
Article
Hemochorial placentation is characterized by trophoblast-directed uterine spiral artery remodeling. The rat and human both possess hemochorial placentation and exhibit remarkable similarities regarding the depth of trophoblast invasion and the extent of uterine vascular modification. In vitro and in vivo research methodologies have been established...
Article
The rat possesses hemochorial placentation with deep intrauterine trophoblast cell invasion and trophoblast-directed uterine spiral artery remodeling; features shared with human placentation. Recognition of these similarities spurred the establishment of in vitro and in vivo research methods using the rat as an animal model to address mechanistic q...
Article
Full-text available
The morphogenesis of the hemochorial placenta is dependent upon the precise expansion and differentiation of trophoblast stem (TS) cells. SATB homeobox 1 (SATB1) and SATB2 are related proteins that have been implicated as regulators of some stem cell populations. SATB1 is highly expressed in TS cells, which prompted an investigation of SATB1 and th...
Article
The rat possesses a hemochorial form of placentation. Pronounced intrauterine trophoblast cell invasion and vascular remodeling characterize this type of placentation. Strain-specific patterns of placentation are evident in the rat. Some rat strains exhibit deep intrauterine trophoblast invasion and an expanded junctional zone [Holtzman Sprague-Daw...
Article
Preeclampsia is associated with increased circulating levels of proinflammatory molecules, such as soluble fms-like tyrosine kinase 1 (sFlt-1) and soluble endoglin (sEng). On release by an inadequately perfused placenta into the maternal circulation, these molecules cause systemic endothelial dysfunction and the associated hypertension and proteinu...
Article
Differentiated trophoblast cell lineages arise from trophoblast stem (TS) cells. To date such a stem cell population has only been established in the mouse. The objective of this investigation was to establish TS cell populations from rat blastocysts. Blastocysts were cultured individually on a feeder layer of rat embryonic fibroblasts (REFs) in fi...
Article
The principal role of the placenta is the maintenance of pregnancy and promotion of fetal growth and viability. The use of transgenic rodents has greatly enhanced our understanding of placental development and function. However, embryonic lethality is often a confounding variable in determining whether a genetic modification adversely affected plac...
Article
Full-text available
Abnormal maternal inflammation during pregnancy is associated with spontaneous pregnancy loss and intrauterine fetal growth restriction. However, the mechanisms responsible for these pregnancy outcomes are not well understood. In this study, we used a rat model to demonstrate that pregnancy loss resulting from aberrant maternal inflammation is clos...
Conference Paper
Full-text available
Background / Purpose: There is evidence that placental anti-angiogenic factors such as soluble fms-related tyrosine kinase 1 (sFlt-1) and soluble Endoglin (sEndoglin) induce systemic maternal endothelial dysfunction thereby contributing to the pathophysiology of pre-eclampsia. Studies have shown that the release of these molecules by the placenta...
Article
4200 Pre-eclampsia, intrauterine growth restriction (IUGR) and spontaneous abortion constitute the majority of serious complications of pregnancy. Women affected with these complications often exhibit excessive systemic inflammation, coagulopathies, and an increased risk of subsequent cardiovascular disease (CVD). Thromboelastography (TEG) has prov...
Article
Approximately 90% of childhood cancers are of unknown etiology; however, it is hypothesized that in utero carcinogen exposure may contribute. Epidemiological studies have correlated parental exposure to benzene with an increased incidence of childhood leukemias. However, mechanisms of benzene-induced carcinogenesis following in utero exposure remai...
Article
The intracellular signaling molecule mammalian target of rapamycin (mTOR) is essential for cell growth and proliferation. It is involved in mouse embryogenesis, murine trophoblast outgrowth and linked to tumor cell invasiveness. In order to assess the role of mTOR in human trophoblast invasion we analyzed the in vitro invasiveness of HTR-8/SVneo im...
Article
The decidual microenvironment is characterized by a unique population of leukocytes composed primarily of CD56(bright) NK cells and macrophages. The latter are situated near trophoblast cells at the fetal-maternal interface and there is evidence that trophoblast cells are capable of recruiting macrophages to this site. This study sought to determin...
Article
Full-text available
The intimate association between maternal and placental tissues elicits an interesting immunological paradox. Placental tissue contains paternal antigens, but under normal circumstances the semi-allogeneic fetus and placenta are not attacked by the maternal immune system. Interestingly, this tolerance to fetal antigens occurs in the presence of a l...
Article
Trophoblast invasion and modification of the spiral arterioles are essential for the establishment of adequate uteroplacental blood flow during pregnancy. However, such vascular remodeling is deficient in preeclampsia. This disease is also associated with increased maternal levels of circulating proinflammatory cytokines such as tumor necrosis fact...
Article
Pre-eclampsia is associated with inadequate cytotrophoblast invasion and remodeling of the uterine spiral arterioles, as well as by an aberrant maternal immune response. This study determined the effect of activated macrophages and one of its products, tumor necrosis factor (TNF)-alpha, on cytotrophoblast invasiveness. Coculture with human lipopoly...
Article
During normal pregnancy, extravillous trophoblast cells invade maternal uterine tissues. The interstitial trophoblast penetrates decidual tissues reaching the inner third of the myometrium. A subset of the interstitial trophoblast, the intramural/endovascular trophoblast transforms uterine spiral arteries into large-bore conduits to enable the adeq...

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