Development and hormonal functions of the human placenta (original) (raw)
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IFPA Award in Placentology Lecture: Biology of the placental syncytiotrophoblast – Myths and facts
Placenta, 2010
About 15 years ago apoptosis was attributed a role in the development of the human placenta. Since then an increasing number of publications has shown that programmed cell death plays an essential role in placental growth and differentiation, especially in the villous trophoblast. During the last ten years a concept was established linking the progress of apoptosis to differentiation of cytotrophoblasts and syncytiotrophoblast. Thus, development and maintenance of the syncytiotrophoblast depends on the precise orchestration of different processes and stages of the apoptosis cascade. This review focuses on the maintenance and growth of the syncytiotrophoblast as well as the deportation of trophoblast material into the maternal circulation. Nuclear morphology is related to transcriptional activity, RNA protection and storage strategies are discussed and the differences between syncytial expression rates of RNA and protein are highlighted. Moreover, deportation of trophoblast fragments is related to the relevant morphological structures (syncytial knots) and to their effects on the maternal system. Finally, different modes of release of trophoblast fragments such as apoptotic, aponecrotic and necrotic are discussed as being responsible for the maternal inflammatory response during pre-eclampsia.
An integrative view on the physiology of human early placental villi
Progress in Biophysics and Molecular Biology, 2014
The placenta is an indispensable organ for intrauterine protection, development and growth of the embryo and fetus. It provides tight contact between mother and conceptus, enabling the exchange of gas, nutrients and waste products. The human placenta is discoidal in shape, and bears a hemo-monochorial interface as well as villous materno-fetal interdigitations. Since Peter Medawar's astonishment to the paradoxical nature of the mother-fetus relationship in 1953, substantial knowledge in the domain of placental physiology has been gathered. In the present essay, an attempt has been made to build an integrated understanding of morphological dynamics, cell biology, and functional aspects of genomic and proteomic expression of human early placental villous trophoblast cells followed by a commentary on the future directions of research in this field.
Human trophoblast differentiates into two pathways: extravillous cytotrophoblasts (EVCT) that invade the uterus wall and villous cytotrophoblasts (VCT) that fuse to form the syncytiotrophoblast (ST) involved in placental exchanges and endocrine function. It is established that hCG is produced and secreted by the ST into the maternal compartment where it plays a key endocrine role and stimulates ST formation in an autocrine manner. Herein, we investigated hCG expression in early placentas by immunohistochemistry using different antibodies. We then compared hCG secretion by primary cultures of VCT and EVCT isolated from the same first trimester human chorionic villi. In situ hCG was immunodetected in EVCT all along their invasive differentiating pathway excepted in cells near the stromal core of the proximal column. hCG expression was confirmed in vitro by immunocytochemistry and hCG secretion quantified in cell supernatants. Interestingly, whereas hCG secretion increased during VCT differentiation into ST (from 60 to 350 UI/L/µg DNA), EVCT secretion remained constant and at a high level during the same culture period (160 UI/L/µg DNA). Our data demonstrated that in addition to the ST, invasive EVCT also expressed and secreted high levels of hCG, suggesting a specific paracrine and/or autocrine role for hCG from EVCT origin.
Aspects of structure and function in human placenta
Current Obstetrics & Gynaecology, 1998
This review summarizes essential features of the functional morphology of human term placenta, concentrating on the processes of proliferation, growth, diffusive transport and microvascular permeability. It introduces the main structures that make up the 'villous membrane' interposed between the maternal and fetal bloods. It then presents an updated view of the proliferation of the principal functional compartment of the membrane, the trophoblast. This is a continuously renewing epithelium: cytotrophoblast cells divide mitotically throughout gestation and are recruited into the overlying syncytium. Contrary to previous dogma, cytotrophoblast is not depleted during gestation. The syncytium loses nuclei in large aggregates (syncytial knots), which detach into the maternal circulation. At least some nuclei are apoptotic and may be phagocytosed by macrophages at extraplacental sites. The villous stroma and fetal endothelium also grow by proliferation. These processes help to expand exchange surface areas and minimize diffusive distances, structural quantities that can be used to estimate placental-oxygen diffusive conductance. The fetal vascular compartment contributes substantially to overall transplacental resistance to solute transport. Fetal vessels are lined by a continuous endothelium with well-differentiated junctional complexes in the paracellular clefts. These complexes contain adhesion molecules that are vulnerable to exogenous agents, and whose expression and localization have been linked with junctional disruption and altered permeability, and altered placental efficiency and permeability. Changes in placental proliferation, growth, diffusive transport and vascular permeability may all play a role in pregnancy-related disorders such as pre-eclampsia and diabetes. OVERVIEW OF PLACENTAL STRUCTURE In the human haemochorial placenta, villous trees bathed by maternal blood circulating through the intervillous space are crucial to placental growth, morphogenesis and function and, hence, to fetal well-being. I,: Because of their number and physical attributes, terminal villi (TV) are the most influential in determining functional activity, and exchanges between maternal and fetal blood occur via the villous
Human Reproduction, 2007
BACKGROUND: Our present knowledge about trophoblast turnover in human first trimester placental villi based on multiparametric examination of proliferation and apoptosis is limited. METHODS: Human villous placentae collected during 6, 7 and 8 weeks (n 5 10/each group) of gestation were examined for trophoblast proliferation and apoptosis based on quantitative analyses of immunopositive Fas, tumor necrosis factor receptor 1 (TNFR1), cytokeratin 18 fragment (18f), number of proliferating cell nuclear antigen (PCNA), Ki67 and terminal deoxynucleotidyl transferasemediated dUTP nick-end labeling (TUNEL) positive nuclei, scores of mitotic and apoptotic indices and ultrastructural characteristics. RESULTS: Mitotic index in cytotrophoblast higher (P < 0.05) at 6 week compared with 7 and 8 weeks of gestation showed significant (P < 0.05) negative correlation between its prevalence and gestational age. Syncytiotrophoblast exhibited higher number of TUNEL positive nuclei (P < 0.01), TUNEL positive apoptotic nuclei (P < 0.05) and apoptotic index (P < 0.05) compared with cytotrophoblast at same gestational age. Positive correlations found between cytokeratin 18f and apoptotic index (P < 0.01), Fas and apoptotic index (P < 0.01), TUNEL positive nuclei and apoptotic index (P < 0.05), cytokeratin 18f and Fas (P < 0.01), whereas cytokeratin 18f (P < 0.05) and Fas (P < 0.05) showed positive correlation only with TUNEL positive apoptotic nuclear data. Phalangeal intrusions of syncytiotrophoblast between transitional cytotrophoblasts showed apposed plasma membranes bearing thickened membrane leaflets, inter-membranous gaps enclosing membranous invaginations, liposome-like particles; patches of membrane seen to be dissolved resulting in cytoplasmic continuity typical of syncytial formation. CONCLUSION: Cellular remodeling of first trimester villous placenta requires a complex homeodynamics involving proliferation in cytotrophoblast, development-associated syncytialization and apoptosis in syncytiotrophoblast.
Evidence for Transcriptional Activity in the Syncytiotrophoblast of the Human Placenta
Placenta, 2009
The aim was to test for evidence of transcriptional activity within the nuclei of the syncytiotrophoblast of the human placenta. The syncytiotrophoblast forms the epithelial covering of the villous tree, and is a multinucleated, terminally-differentiated syncytium generated through fusion of the underlying progenitor cytotrophoblast cells. Its nuclei are heterogeneous with respect to chromatin condensation, and previous functional studies of 3H-uridine uptake in vitro have indicated that they are transcriptionally inactive. This observation is surprising given the key roles this tissue plays in active transport, hormone synthesis and metabolic regulation, and has widespread implications for trophoblast physiology and pathophysiology. We used three different approaches to look for evidence of transcriptional activity. First, immunofluorescence staining was performed on paraffin-embedded early pregnancy and term placental villi, using an antibody directed specifically against the actively transcribing form of RNA polymerase II. Second, a nucleoside incorporation assay was applied to placental villi maintained in short-term culture, with and without the transcription blocker a-amanitin. Third, histone modifications associated with active chromatin were identified by immunohistochemistry and immunofluorescence. Each of these methods showed transcription to be occurring in a proportion of syncytiotrophoblast nuclei, with qualitative evidence for transcription being more abundant in the first trimester than at term. These findings correlated with electron microscopical observations of prominent nucleoli within the nuclei, particularly during early pregnancy, signifying transcription of ribosomal RNA. Contrary to previous findings, these results confirm that a proportion of syncytiotrophoblast nuclei actively produce mRNA transcripts.
Syncytial Knots, Sprouts, Apoptosis, and Trophoblast Deportation from the Human Placenta
Taiwanese Journal of Obstetrics and Gynecology, 2009
The syncytiotrophoblast (STB) that forms the epithelial covering of the placental villous tree has a unique cell biology on account of its syncytial nature. The tissue is in a terminally-differentiated, postmitotic state, and expands through the recruitment by fusion of underlying progenitor cytotrophoblast cells. This process occurs from the time of implantation until term, and so its nuclei will be of various ages, producing a spectrum of contrasting appearances; whilst some are euchromatic, others display dense condensations of heterochromatin, the latter often aggregating to form clusters referred to as syncytial knots. These appearances have led to the suggestion that knots are apoptotic, and a hypothesis has developed that the nuclei are transcriptionally inactive and transit through the STB before being shed into the maternal circulation. Here, we review the evidence for this hypothesis, looking at the morphology of the nuclei, their number throughout gestation, evidence of transcriptional activity, and trophoblast deportation. We conclude that there is little evidence to support the concept that turnover of syncytial nuclei takes place in the normal placenta, or that this occurs through an apoptotic-related process. Instead, we suggest that a proportion of syncytial nuclei are transcriptionally active, that epigenetic modifications underlie the changes in chromatin appearance, and that syncytial nuclei continue to accumulate until term. We recognize that apoptotic changes can occur in pathologic pregnancies, but consider the deportation of trophoblast that has been linked to preeclampsia to be most likely of necrotic origin following ischemic injury.