-
Frontiers in Bioscience (Scholar... Jan 2012Attainment of successful implantation depends upon the synchronized changes in the endometrium before and after the arrival of blastocyst into the uterine cavity. The... (Review)
Review
Attainment of successful implantation depends upon the synchronized changes in the endometrium before and after the arrival of blastocyst into the uterine cavity. The cues obtained from the receptive endometrium helps in proliferation and differentiation of the trophoblast cells. During the course of invasive differentiation, the trophoblast cells undergo several morphological, biochemical and molecular changes to gain the invasive capabilities. In turn, close apposition of the developing embryo brings out functional and morphological changes into the hormone primed receptive endometrium. Global gene expression profiling of the endometrium in response to the developing embryo or in response to the pregnancy hormone, human chorionic gonadotropin, in primate and human models, suggest that the endometrial-embryo cross-talk mainly influences three biological processes. Biological processes getting influenced by the blastocyst "signals" are associated with immunomodulation, biosensing and invasion. Pro- and anti-invasive paracrine factors expressed by different endometrial cell populations regulate the trophoblast invasion through activation of diverse signaling pathways. Identification of the gene signatures involved in embryo-endometrial dialogue would enhance our understanding about the pathologies like miscarriages and endometriosis.
Topics: Animals; Blastocyst; Embryo Implantation; Endometrium; Female; Humans; Pregnancy; Signal Transduction; Trophoblasts
PubMed: 22202114
DOI: 10.2741/s323 -
Cell Adhesion & Migration Mar 2016The proper establishment and organogenesis of the placenta is crucial for intrauterine fetal growth and development. Endometrial invasion by the extravillous trophoblast... (Review)
Review
The proper establishment and organogenesis of the placenta is crucial for intrauterine fetal growth and development. Endometrial invasion by the extravillous trophoblast cells, as well as formation of the syncytiotrophoblast (STB), are of vital importance for placental function. Trophoblast migration and invasion is often compared to tumor metastasis, which uses many of the same molecular mechanisms. However, unlike cancer cells, both initiation and the extent of trophoblast invasion are tightly regulated by feto-maternal cross-talk, which when perturbed, results in a wide range of abnormalities. Multiple factors control the trophoblast, including cytokines and hormones, which are subject to transcriptional regulatory networks. The relevance of epigenetics in transcriptional regulation of trophoblast differentiation and invasion, as well as in the onset of placenta-related pregnancy disorders, became recognized decades ago. Although, there has been tremendous progress in uncovering the molecular foundation of placental development, there is still much to be learned about the epigenetic machinery, and its role in trophoblast differentiation and invasion. This review will provide an overview of the epigenetic control of trophoblast differentiation and invasion. It will also highlight the major epigenetic mechanisms involved in pregnancy complications related to placental deficiencies.
Topics: Cell Differentiation; Cell Movement; Epigenesis, Genetic; Female; Histones; Humans; Pregnancy; Protein Processing, Post-Translational; Trophoblasts
PubMed: 26745760
DOI: 10.1080/19336918.2015.1098800 -
Cell Adhesion & Migration Mar 2016Proper placental development and function is crucial for a healthy pregnancy, and there has been substantial research to identify markers of placental dysfunction for... (Review)
Review
Proper placental development and function is crucial for a healthy pregnancy, and there has been substantial research to identify markers of placental dysfunction for the early detection of pregnancy complications. Low first-trimester levels of a disintegrin and metalloproteinase 12 (ADAM12) and pregnancy-associated plasma protein-A (PAPP-A) have been consistently associated with the subsequent development of preeclampsia and fetal growth restriction. These molecules are both metalloproteinases secreted by the placenta that cleave insulin-like growth factor binding proteins (IGFBPs), although ADAM12 also has numerous other substrates. Recent work has identified ADAM12, and particularly its shorter variant, ADAM12S, as a regulator of the migration and invasion of trophoblasts into the lining of the uterus, a critical step in normal placental development. While the mechanisms underlying this regulation are not yet clear, they may involve the liberation of heparin-binding EGF-like growth factor (HB-EGF) and/or IGFs from IGFBPs. In contrast, there has been relatively little functional work examining PAPP-A or the IGFBP substrates of ADAM12 and PAPP-A. Understanding the functions of these markers and the mechanisms underlying their association with disease could improve screening strategies and enable the development of new therapeutic interventions.
Topics: ADAM12 Protein; Animals; Biomarkers; Female; Humans; Pregnancy; Pregnancy Outcome; Pregnancy Trimester, First; Pregnancy-Associated Plasma Protein-A; Trophoblasts
PubMed: 26417939
DOI: 10.1080/19336918.2015.1083668 -
Biology of Reproduction Jan 2023The placenta is an important organ for the exchange of substances between the fetus and the mother, hormone secretion, and fetoplacental immunological defense. Placenta... (Review)
Review
The placenta is an important organ for the exchange of substances between the fetus and the mother, hormone secretion, and fetoplacental immunological defense. Placenta has an organ-specific distribution of ion channels and trophoblasts, and placental vessels express a large number of ion channels. Several placental housekeeping activities and pregnancy complications are at least partly controlled by ion channels, which are playing an important role in regulating hormone secretion, trophoblastic homeostasis, ion transport, and vasomotor activity. The function of several placental ion channels (Na, Ca, and Cl ion channels, cation channel, nicotinic acetylcholine receptors, and aquaporin-1) is known to be influenced by chemical exposure, i.e., their responses to different chemicals have been tested and confirmed in experimental models. Here, we review the possibility that placental ion channels are targets of toxicological concern in terms of placental function, fetal growth, and development.
Topics: Pregnancy; Female; Humans; Placenta; Ion Channels; Trophoblasts; Biological Transport; Hormones
PubMed: 36173899
DOI: 10.1093/biolre/ioac186 -
The International Journal of... 2010Invasion of placental trophoblasts into uterine tissue and vessels is an essential process of human pregnancy and fetal development. Due to their remarkable plasticity... (Review)
Review
Invasion of placental trophoblasts into uterine tissue and vessels is an essential process of human pregnancy and fetal development. Due to their remarkable plasticity invasive trophoblasts fulfil numerous functions, i.e. anchorage of the placenta, secretion of hormones, modulation of decidual angiogenesis/lymphangiogenesis and remodelling of maternal spiral arteries. The latter is required to increase blood flow to the placenta, thereby ensuring appropriate transfer of nutrients and oxygen to the developing fetus. Since failures in vascular changes of the placental bed are associated with pregnancy diseases such as preeclampsia or intrauterine growth restriction, basic research in this particular field focuses on molecular mechanisms controlling trophoblast invasion under physiological and pathological conditions. Throughout the years, an increasing number of growth factors, cytokines and angiogenic molecules controlling trophoblast motility have been identified. These factors are secreted from numerous cells such as trophoblast, maternal epithelial and stromal cells, as well as uterine NK cells and macrophages, suggesting that a complex network of cell types, mediators and signalling pathways regulates trophoblast invasiveness. Whereas essential features of the invasive trophoblast such as expression of critical proteases and adhesion molecules have been well characterised, the interplay between different cell types and growth factors and the cross-talk between distinct signalling cascades remain largely elusive. Similarly, key-regulatory transcription factors committing and differentiating invasive trophoblasts are mostly unknown. This review will summarise our current understanding of growth factors and signal transduction pathways regulating human trophoblast invasion/migration, as well as give insights into novel mechanisms involved in the particular differentiation process.
Topics: Female; Humans; Intercellular Signaling Peptides and Proteins; Placenta; Pregnancy; Signal Transduction; Trophoblasts
PubMed: 19876833
DOI: 10.1387/ijdb.082769mk -
Reproductive Biology and Endocrinology... Feb 2007The trophoblast, i.e. the peripheral part of the human conceptus, exerts a crucial role in implantation and placentation. Both processes properly occur as a consequence... (Review)
Review
The trophoblast, i.e. the peripheral part of the human conceptus, exerts a crucial role in implantation and placentation. Both processes properly occur as a consequence of an intimate dialogue between fetal and maternal tissues, fulfilled by membrane ligands and receptors, as well as by hormone and local factor release. During blastocyst implantation, generation of distinct trophoblast cell types begins, namely the villous and the extravillous trophoblast, the former of which is devoted to fetal-maternal exchanges and the latter binds the placental body to the uterine wall. Physiological placentation is characterized by the invasion of the uterine spiral arteries by extravillous trophoblast cells arising from anchoring villi. Due to this invasion, the arterial structure is replaced by amorphous fibrinoid material and endovascular trophoblastic cells. This transformation establishes a low-resistance, high-capacity perfusion system from the radial arteries to the intervillous space, in which the villous tree is embedded. The physiology of pregnancy depends upon the orderly progress of structural and functional changes of villous and extravillous trophoblast, whereas a derangement of such processes can lead to different types of complications of varying degrees of gravity, including possible pregnancy loss and maternal life-threatening diseases. In this review we describe the mechanisms which regulate trophoblast differentiation, proliferation, migration and invasiveness, and the alterations in these mechanisms which lead to pathological conditions. Furthermore, based on the growing evidence that proper inflammatory changes and oxidative balance are needed for successful gestation, we explain the mechanisms by which agents able to influence such processes may be useful in the prevention and treatment of pregnancy disorders.
Topics: Cell Differentiation; Embryo Implantation; Female; Humans; Oxidative Stress; Pregnancy; Pregnancy Complications; Trophoblasts
PubMed: 17288592
DOI: 10.1186/1477-7827-5-6 -
Biophysical Journal Dec 2018It has long been recognized that mechanical forces underlie mammalian embryonic shape changes. Before gastrulation, the blastocyst embryo undergoes significant shape...
It has long been recognized that mechanical forces underlie mammalian embryonic shape changes. Before gastrulation, the blastocyst embryo undergoes significant shape changes, namely, the blastocyst cavity emerges and expands, and the inner cell mass (ICM) forms and changes in shape. The embryo's inner pressure has been hypothesized to be the driving mechanical input that causes the expansion of the blastocyst cavity and the shape changes of the ICM. However, how the inner pressure and the mechanics of the trophoblast and the ICM change during development is unknown because of the lack of a suitable tool for quantitative characterization. This work presents a laser-assisted magnetic tweezer technique for measuring the inner pressure and Young's modulus of the trophoblast and ICM of the blastocyst-stage mouse embryo. The results quantitatively showed that the inner pressure and Young's modulus of the trophoblast and ICM all increase during progression of mouse blastocysts, providing useful data for understanding how mechanical factors are physiologically integrated with other cues to direct embryo development.
Topics: Animals; Biomechanical Phenomena; Blastocyst; Mice; Pressure; Trophoblasts
PubMed: 30509858
DOI: 10.1016/j.bpj.2018.11.008 -
Development (Cambridge, England) Aug 2023The invasive trophoblast cell lineages in rat and human share crucial responsibilities in establishing the uterine-placental interface of the hemochorial placenta. These...
The invasive trophoblast cell lineages in rat and human share crucial responsibilities in establishing the uterine-placental interface of the hemochorial placenta. These observations have led to the rat becoming an especially useful animal model for studying hemochorial placentation. However, our understanding of similarities or differences between regulatory mechanisms governing rat and human invasive trophoblast cell populations is limited. In this study, we generated single-nucleus ATAC-seq data from gestation day 15.5 and 19.5 rat uterine-placental interface tissues, and integrated the data with single-cell RNA-seq data generated at the same stages. We determined the chromatin accessibility profiles of invasive trophoblast, natural killer, macrophage, endothelial and smooth muscle cells, and compared invasive trophoblast chromatin accessibility with extravillous trophoblast cell accessibility. In comparing chromatin accessibility profiles between species, we found similarities in patterns of gene regulation and groups of motifs enriched in accessible regions. Finally, we identified a conserved gene regulatory network in invasive trophoblast cells. Our data, findings and analysis will facilitate future studies investigating regulatory mechanisms essential for the invasive trophoblast cell lineage.
Topics: Animals; Pregnancy; Rats; Cell Nucleus; Chromatin; Gene Regulatory Networks; Placenta; Single-Cell Gene Expression Analysis; Transcription Factors; Trophoblasts; Uterus; Female
PubMed: 37417811
DOI: 10.1242/dev.201826 -
Systems Biology in Reproductive Medicine Apr 2010Stress causes decreased cell accumulation in early periimplantation embryos and the placental trophoblast stem cells derived from them. Benzopyrene and many other... (Review)
Review
Stress causes decreased cell accumulation in early periimplantation embryos and the placental trophoblast stem cells derived from them. Benzopyrene and many other stressors activate stress enzymes that lead to suppressed stem cell accumulation through diminished proliferation and increased apoptosis. Trophoblast stem cells proliferate and a subpopulation of early postimplantation trophoblast cells differentiate to produce the first placental hormones that arise in the implanting conceptus. These hormones mediate antiluteolytic effects that enable the continuation of a successful implantation. The normal determination and differentiation of placental trophoblast stem cells is dependent upon a series of transcription factors. But, these transcription factors can also be modulated by stress through the activity of stress enzymes. This review enumerates and analyzes recent reports on the effects of benzopyrene on placental function in terms of the emerging paradigm that placental differentiation from stem cells can be regulated when insufficient production of stem cells is caused by stress. In addition, we review the other effects caused by benzopyrene throughout placental development.
Topics: Animals; Benzopyrenes; Blastocyst; Cell Differentiation; Cell Lineage; Embryo Implantation; Female; Humans; Placenta; Pregnancy; Smoking; Stem Cells; Stress, Physiological; Transcription Factors; Trophoblasts
PubMed: 20377314
DOI: 10.3109/19396360903431638 -
Trends in Endocrinology and Metabolism:... Jul 2020Endocrine disrupting chemicals (EDCs) are chemicals that can interfere with normal endocrine signals. Human exposure to EDCs is particularly concerning during vulnerable... (Review)
Review
Endocrine disrupting chemicals (EDCs) are chemicals that can interfere with normal endocrine signals. Human exposure to EDCs is particularly concerning during vulnerable periods of life, such as pregnancy. However, often overlooked is the effect that EDCs may pose to the placenta. The abundance of hormone receptors makes the placenta highly sensitive to EDCs. We have reviewed the most recent advances in our understanding of EDC exposures on the development and function of the placenta such as steroidogenesis, spiral artery remodeling, drug-transporter expression, implantation and cellular invasion, fusion, and proliferation. EDCs reviewed include those ubiquitous in the environment with available human biomonitoring data. This review also identifies critical gaps in knowledge to drive future research in the field.
Topics: Animals; Endocrine Disruptors; Endocrine System; Female; Humans; Placenta; Pregnancy; Trophoblasts
PubMed: 32249015
DOI: 10.1016/j.tem.2020.03.003