Placental-related fetal growth restriction arises primarily due to deficient remodeling of the uterine spiral arteries supplying the placenta during early pregnancy. The resultant malperfusion ...induces cell stress within the placental tissues, leading to selective suppression of protein synthesis and reduced cell proliferation. These effects are compounded in more severe cases by increased infarction and fibrin deposition. Consequently, there is a reduction in villous volume and surface area for maternal-fetal exchange. Extensive dysregulation of imprinted and nonimprinted gene expression occurs, affecting placental transport, endocrine, metabolic, and immune functions. Secondary changes involving dedifferentiation of smooth muscle cells surrounding the fetal arteries within placental stem villi correlate with absent or reversed end-diastolic umbilical artery blood flow, and with a reduction in birthweight. Many of the morphological changes, principally the intraplacental vascular lesions, can be imaged using ultrasound or magnetic resonance imaging scanning, enabling their development and progression to be followed in vivo. The changes are more severe in cases of growth restriction associated with preeclampsia compared to those with growth restriction alone, consistent with the greater degree of maternal vasculopathy reported in the former and more extensive macroscopic placental damage including infarcts, extensive fibrin deposition and microscopic villous developmental defects, atherosis of the spiral arteries, and noninfectious villitis. The higher level of stress may activate proinflammatory and apoptotic pathways within the syncytiotrophoblast, releasing factors that cause the maternal endothelial cell activation that distinguishes between the 2 conditions. Congenital anomalies of the umbilical cord and placental shape are the only placental-related conditions that are not associated with maldevelopment of the uteroplacental circulation, and their impact on fetal growth is limited.
Abstract The placenta accreta spectrum (PAS) is a complex obstetric complication associated with a high maternal morbidity. It is a relatively new disorder of placentation, and is the consequence of ...damage to the endometrium-myometrial interface of the uterine wall. When first described 80 years ago, it mainly occurred after manual removal of the placenta, uterine curettage or endometritis. Superficial damage leads primarily to an abnormally adherent placenta, and is diagnosed as the complete or partial absence of the decidua on histology. Today, the main cause of PAS is uterine surgery and, in particular, the uterine scar secondary to a caesarean delivery. In the absence of endometrial re-epithelialization of the scar area the trophoblast and villous tissue can invade deeply within the myometrium, including its circulation, and reach the surrounding pelvic organs. The cellular changes in the trophoblast observed in PAS are probably secondary to the unusual myometrial environment in which it develops, and not to a primary defect of trophoblast biology leading to excessive invasion of the myometrium. PAS was separated by pathologists into three categories: placenta creta (PC) when the villi simply adhere to the myometrium, placenta increta (PI) when the villi invade the myometrium, and placenta percreta (PP) where the villi invade the full thickness of the myometrium. Several prenatal ultrasound signs of PAS have been reported over the last 35 years, principally the disappearance of the normal utero-placental interface (clear zone), extreme thinning of the underlying myometrium and vascular changes within the placenta (lacunae) and placental bed (hypervascularity). The pathophysiological basis of these signs is due to permanent damage of the uterine wall as far as the serosa, with placental tissue reaching the deep uterine circulation. Adherent and invasive placentation may co-exist in the same placental bed and evolve with advancing gestation. This may explain why no single, or set combination of, ultrasound sign(s) has been found to be specific for the depth of abnormal placentation, and accurate for the differential diagnosis between adherent and invasive placentation. Correlation of pathological and clinical findings with the prenatal imaging is essential to improve screening, diagnosis and management of PAS, and standardised protocols need to be developed.
Despite increased participation opportunities for girls and women in sport, they are underrepresented in leadership positions at all levels of sport. The objective of this review is to provide a ...multilevel examination of available scholarship that contributes to understanding why there are so few women in leadership positions within sport. From a macro-level perspective, scholarship regarding the institutionalized practices of gender in sport is examined. The meso-level review includes stereotyping of leaders, issues of discrimination, and gendered organizational cultures. Finally research reviewed at the micro-level explores women's expectations in leadership positions, occupational turnover intentions, and the influence of symbolic interactionism on women's career advancement. In addition, the author identifies new research areas and additional recommendations for how best to increase the number of women in leadership positions in sport.
The placenta: a multifaceted, transient organ Burton, Graham J.; Fowden, Abigail L.
Philosophical transactions of the Royal Society of London. Series B. Biological sciences,
03/2015, Letnik:
370, Številka:
1663
Journal Article
Recenzirano
Odprti dostop
The placenta is arguably the most important organ of the body, but paradoxically the most poorly understood. During its transient existence, it performs actions that are later taken on by diverse ...separate organs, including the lungs, liver, gut, kidneys and endocrine glands. Its principal function is to supply the fetus, and in particular, the fetal brain, with oxygen and nutrients. The placenta is structurally adapted to achieve this, possessing a large surface area for exchange and a thin interhaemal membrane separating the maternal and fetal circulations. In addition, it adopts other strategies that are key to facilitating transfer, including remodelling of the maternal uterine arteries that supply the placenta to ensure optimal perfusion. Furthermore, placental hormones have profound effects on maternal metabolism, initially building up her energy reserves and then releasing these to support fetal growth in later pregnancy and lactation post-natally. Bipedalism has posed unique haemodynamic challenges to the placental circulation, as pressure applied to the vena cava by the pregnant uterus may compromise venous return to the heart. These challenges, along with the immune interactions involved in maternal arterial remodelling, may explain complications of pregnancy that are almost unique to the human, including pre-eclampsia. Such complications may represent a trade-off against the provision for a large fetal brain.
Many agricultural studies have observed a relationship between farmer demographic characteristics and environmental behaviours. These relationships are frequently employed in the construction of ...models, the identification of farmer types, or as part of more descriptive analyses aimed at understanding farmers' environmental behaviour. However, they have also often been found to be inconsistent or contradictory. Although a considerable body of literature has built up around the subject area, research has a tendency to focus on factors such as the direction, strength and consistency of the relationship – leaving the issue of causality largely to speculation. This review addresses this gap by reviewing literature on 4 key demographic variables: age, experience, education, and gender for hypothesised causal links. Overall the review indicates that the issue of causality is a complex one. Inconsistent relationships can be attributed to the presence of multiple causal pathways, the role of scheme factors in determining which pathway is important, inadequately specified measurements of demographic characteristics, and the treatment of non-linear causalities as linear. In addition, all demographic characteristics were perceived to be influenced (to varying extents) by cultural-historical patterns leading to cohort effects or socialised differences in the relationship with environmental behaviour. The paper concludes that more work is required on the issue of causality.
•Literature on farmer demographic variables and environmental behaviour is reviewed.•Causal explanations for the relationships are assessed.•A framework diagram is constructed to examine linkages between variables.•Six recommendations are made to assist future research.
AbstractPre-eclampsia is a common disorder that particularly affects first pregnancies. The clinical presentation is highly variable but hypertension and proteinuria are usually seen. These systemic ...signs arise from soluble factors released from the placenta as a result of a response to stress of syncytiotrophoblast. There are two sub-types: early and late onset pre-eclampsia, with others almost certainly yet to be identified. Early onset pre-eclampsia arises owing to defective placentation, whilst late onset pre-eclampsia may center around interactions between normal senescence of the placenta and a maternal genetic predisposition to cardiovascular and metabolic disease. The causes, placental and maternal, vary among individuals. Recent research has focused on placental-uterine interactions in early pregnancy. The aim now is to translate these findings into new ways to predict, prevent, and treat pre-eclampsia.
Placental Origins of Chronic Disease Burton, Graham J; Fowden, Abigail L; Thornburg, Kent L
Physiological reviews,
10/2016, Letnik:
96, Številka:
4
Journal Article
Recenzirano
Odprti dostop
Epidemiological evidence links an individual's susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically this should not be unexpected, ...for organ systems are at their most plastic when progenitor cells are proliferating and differentiating. Influences operating at this time can permanently affect their structure and functional capacity, and the activity of enzyme systems and endocrine axes. It is now appreciated that such effects lay the foundations for a diverse array of diseases that become manifest many years later, often in response to secondary environmental stressors. Fetal development is underpinned by the placenta, the organ that forms the interface between the fetus and its mother. All nutrients and oxygen reaching the fetus must pass through this organ. The placenta also has major endocrine functions, orchestrating maternal adaptations to pregnancy and mobilizing resources for fetal use. In addition, it acts as a selective barrier, creating a protective milieu by minimizing exposure of the fetus to maternal hormones, such as glucocorticoids, xenobiotics, pathogens, and parasites. The placenta shows a remarkable capacity to adapt to adverse environmental cues and lessen their impact on the fetus. However, if placental function is impaired, or its capacity to adapt is exceeded, then fetal development may be compromised. Here, we explore the complex relationships between the placental phenotype and developmental programming of chronic disease in the offspring. Ensuring optimal placentation offers a new approach to the prevention of disorders such as cardiovascular disease, diabetes, and obesity, which are reaching epidemic proportions.
Abstract
BACKGROUND
In humans, inadequate trophoblast invasion into the decidua is associated with the ‘great obstetrical syndromes’ which include pre-eclampsia, foetal growth restriction (FGR) and ...stillbirth. The mechanisms regulating invasion remain poorly understood, although interactions with the uterine environment are clearly of central importance. Extravillous trophoblast (EVT) cells invade the uterus and transform the spiral arteries. Progress in understanding how they invade has been limited due to the lack of good in vitro models. Firstly, there are no non-malignant cell lines that have an EVT phenotype. Secondly, the invasion assays used are of limited use for the small numbers of primary EVT available from first-trimester placentas. We discuss recent progress in this field with the generation of new EVT lines and invasion assays using microfluidic technology.
OBJECTIVE AND RATIONALE
Our aim is to describe the established models used to study human trophoblast invasion in vivo and in vitro. The difficulties of obtaining primary cells and cell lines that recapitulate the phenotype of EVT are discussed together with the advantages and pitfalls of the different invasion assays. We compare these traditional end point assays to microfluidic assays where the dynamics of migration can be measured.
SEARCH METHODS
Relevant studies were identified by PubMed search, last updated on February 2020. A search was conducted to determine the number of journal articles published using the cell lines JEG-3, BeWo, JAR, HTR-8/Svneo, Swan-71 and primary human extravillous trophoblast in the last 5 years.
OUTCOMES
Deep trophoblast invasion into the maternal decidua is a particular feature of human pregnancy. This invasion needs to be finely regulated to allocate resources between mother and baby. A reliable source of EVT is needed to study in vitro how the uterine environment regulates this process. First, we critically discuss the issues with the trophoblast cell lines currently used; for example, most of them lack expression of the defining marker of EVT, HLA-G. Recently, advances in human stem cell and organoid technology have been applied to extraembryonic tissues to develop trophoblast cell lines that can grow in two (2D) and three dimensions (3D) and differentiate to EVT. This means that the ‘trophoblast’ cell lines currently in use should rapidly become obsolete. Second, we critically discuss the problems with assays to study trophoblast invasion. These lack physiological relevance and have simplified migration dynamics. Microfluidic assays are a powerful tool to study cell invasion because they require only a few cells, which are embedded in 3D in an extracellular matrix. Their major advantage is real-time monitoring of cell movement, enabling detailed analysis of the dynamics of trophoblast migration.
WIDER IMPLICATIONS
Trophoblast invasion in the first trimester of pregnancy remains poorly understood despite the importance of this process in the pathogenesis of pre-eclampsia, FGR, stillbirth and recurrent miscarriage. The new technologies described here will allow investigation into this critical process.
The window between snow melt and leaf flush in broadleaf trees defines a critical period of wildfire susceptibility, especially in western boreal forests. Questions remain about how a warming climate ...might affect those two processes that bookend the spring fire season.
Abstract Many complications of pregnancy have their pathophysiological roots in the early stages of placentation. Impaired trophoblast invasion and deficient remodelling of the maternal spiral ...arteries are a common feature. While malperfusion of the placenta may underpin cases of fetal growth restriction and early-onset pre-eclampsia, the mechanistic links to spontaneous miscarriage, pre-term labour and premature rupture of the membranes are less obvious. Here, we speculate that formation of a well-developed cytotrophoblastic shell at the maternal-fetal interface is crucial for pregnancy success. Initially, extravillous trophoblast cells differentiate from the outer layer of the shell in contact with the endometrium. Impaired development may thus contribute to reduced invasion and deficient remodelling. In addition, the extent of the shell influences the timing and spatial configuration of onset of the maternal arterial circulation. A thin and fragmentary shell results in premature and disorganised onset, leading to spontaneous miscarriage. In less severe cases it may predispose to haemorrhage at the interface and formation of intrauterine haematomas. If pregnancy continues, these haematomas may act as a source of oxidative stress, promoting senescence and weakening of the membranes, and stimulating inflammation in the uterine wall and premature contractions. Formation of the shell is dependent on proliferation of cytotrophoblast progenitor cells during the first weeks after implantation, when the developing placenta is supported by histotrophic nutrition from endometrial glands. Hence, we propose the fitness of the endometrium prior to conception, and the peri-conceptional dialogue between the endometrium and the trophoblast is critical for avoidance of later complications of pregnancy.
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