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Physiological Reviews Oct 2016Epidemiological evidence links an individual's susceptibility to chronic disease in adult life to events during their intrauterine phase of development. Biologically... (Review)
Review
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.
Topics: Animals; Chronic Disease; Female; Fetal Development; Humans; Maternal-Fetal Exchange; Placenta; Placentation; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 27604528
DOI: 10.1152/physrev.00029.2015 -
Cells Jan 2023The first studies suggesting that abnormal expression of galectins is associated with cancer were published more than 30 years ago. Today, the role of galectins in... (Review)
Review
The first studies suggesting that abnormal expression of galectins is associated with cancer were published more than 30 years ago. Today, the role of galectins in cancer is relatively well established. We know that galectins play an active role in many types of cancer by regulating cell growth, conferring cell death resistance, or inducing local and systemic immunosuppression, allowing tumor cells to escape the host immune response. However, most of these studies have focused on very few galectins, most notably galectin-1 and galectin-3, and more recently, galectin-7 and galectin-9. Whether other galectins play a role in cancer remains unclear. This is particularly true for placental galectins, a subgroup that includes galectin-13, -14, and -16. The role of these galectins in placental development has been well described, and excellent reviews on their role during pregnancy have been published. At first sight, it was considered unlikely that placental galectins were involved in cancer. Yet, placentation and cancer progression share several cellular and molecular features, including cell invasion, immune tolerance and vascular remodeling. The development of new research tools and the concomitant increase in database repositories for high throughput gene expression data of normal and cancer tissues provide a new opportunity to examine the potential involvement of placental galectins in cancer. In this review, we discuss the possible roles of placental galectins in cancer progression and why they should be considered in cancer studies. We also address challenges associated with developing novel research tools to investigate their protumorigenic functions and design highly specific therapeutic drugs.
Topics: Pregnancy; Female; Humans; Placenta; Galectins; Neoplasms; Galectin 3; Placentation
PubMed: 36766779
DOI: 10.3390/cells12030437 -
Fertility and Sterility Sep 2023
Topics: Pregnancy; Female; Humans; Placentation; Placenta; Placenta Diseases; Abortion, Habitual
PubMed: 37392784
DOI: 10.1016/j.fertnstert.2023.06.031 -
Nature Communications Feb 2024Proper placental development in early pregnancy ensures a positive outcome later on. The developmental relationship between the placenta and embryonic organs, such as...
Proper placental development in early pregnancy ensures a positive outcome later on. The developmental relationship between the placenta and embryonic organs, such as the heart, is crucial for a normal pregnancy. However, the mechanism through which the placenta influences the development of embryonic organs remains unclear. Trophoblasts fuse to form multinucleated syncytiotrophoblasts (SynT), which primarily make up the placental materno-fetal interface. We discovered that endogenous progesterone immunomodulatory binding factor 1 (PIBF1) is vital for trophoblast differentiation and fusion into SynT in humans and mice. PIBF1 facilitates communication between SynT and adjacent vascular cells, promoting vascular network development in the primary placenta. This process affected the early development of the embryonic cardiovascular system in mice. Moreover, in vitro experiments showed that PIBF1 promotes the development of cardiovascular characteristics in heart organoids. Our findings show how SynTs organize the barrier and imply their possible roles in supporting embryogenesis, including cardiovascular development. SynT-derived factors and SynT within the placenta may play critical roles in ensuring proper organogenesis of other organs in the embryo.
Topics: Animals; Female; Humans; Mice; Pregnancy; Cell Differentiation; Embryonic Development; Placenta; Placentation; Pregnancy Proteins; Suppressor Factors, Immunologic; Trophoblasts; Cardiovascular System
PubMed: 38374152
DOI: 10.1038/s41467-024-45647-8 -
Reproductive Sciences (Thousand Oaks,... Feb 2018Humans are one of the few mammalian viviparous species in which pregnancy is extended beyond the luteal phase, the phase during which progesterone is synthesized by the... (Review)
Review
Humans are one of the few mammalian viviparous species in which pregnancy is extended beyond the luteal phase, the phase during which progesterone is synthesized by the maternal ovary. Instead, it is the fetal placenta that produces progesterone throughout the latter 2 trimesters of human pregnancy. The placenta is developmentally crucial for reproductive success and is the most conspicuous anatomical novelty of placental mammals. However, before it can exert its dual functions as both an endocrine organ and an organ capable of facilitating gas and nutrient exchange, enormous changes must take place within the uterus to not only tolerate the presence of this hemiallogeneic tissue but to also accommodate and support placental development. The most dramatic of these changes is endometrial decidualization, the origin of which coincides in evolutionary history with invasive placentation. This article builds on the observation that the physiological changes that occur during the nonpregnant secretory phase of the uterine cycle in women are remarkably similar to that seen during pregnancy. The fundamental characteristics of human pregnancy (including endometrial decidualization followed several months later by intrauterine inflammation, uterine contractions, and discharge of the decidual lining from the uterine cavity) are present already in the nonpregnant menstrual cycle and are thus independent of the fetus. We hypothesize that many of the physiological defects that lead to complications during pregnancy and parturition are detectable already during spontaneous decidualization in the nonpregnant state and at the onset of menstruation, and can thus be determined before the onset of pregnancy.
Topics: Embryo Implantation; Endometrium; Female; Humans; Menstruation; Parturition; Placenta; Placentation; Pregnancy; Uterus
PubMed: 28826363
DOI: 10.1177/1933719117725830 -
Results and Problems in Cell... 2024Placentation is the development of a temporary arrangement between the maternal uterus and blastocyst-derived placental tissues designed to transport nutrients, gases,... (Review)
Review
Placentation is the development of a temporary arrangement between the maternal uterus and blastocyst-derived placental tissues designed to transport nutrients, gases, and other products from the mother to the embryo and fetus. Placentation differs histologically among species, but all types of placentation share the common trait of utilizing highly complex cell-to-cell and tissue-to-tissue morphological and biochemical interactions to remodel the uterine-placental interface. An elegant series of electron microscopy (EM) images supports the classification of ovine placentation as synepitheliochorial, because uterine luminal epithelial (LE) cells are maintained at the uterine-placental interface through incorporation into trophoblast syncytial plaques. In this review, we utilize immunofluorescence microscopy to provide further insights into early syncytialization of the ovine placenta. These observations, based on results using immunofluorescence microscopy, complement and expand, not replace, our understanding of syncytialization in sheep.
Topics: Pregnancy; Sheep; Animals; Female; Placenta; Placentation; Trophoblasts; Blastocyst; Fetus
PubMed: 37996676
DOI: 10.1007/978-3-031-37936-9_7 -
Placenta Dec 2021Placenta in certain species including the human has evolved as a highly invasive tumor-like organ invading the uterus aned its vasculature to derive oxygen and nutrients... (Review)
Review
Placenta in certain species including the human has evolved as a highly invasive tumor-like organ invading the uterus aned its vasculature to derive oxygen and nutrients for the fetus and exchange waste products. While several excellent reviews have been written comparing hemochorial placentation with tumors, no comprehensive review is available dealing with mechanistic insights into what makes them different, and what tumor biologists can learn from placental biologists, and vice versa. In this review, we analyze the structure-function relationship of the human placenta, emphasizing the functional need of the spatio-temporally orchestrated trophoblast invasiveness for fetal development and growth, and pathological consequences of aberrant invasiveness for fetal and maternal health. We then analyze similarities and differences between the placenta and invasive tumors in terms of hallmarks of cancer, some key molecules regulating their invasive functions, and how placental cancers (choriocarcinomas) or other cancers become refractory or even addicted to these invasion-restraining molecules. We cite in vitro models of human trophoblast and choriocarcinoma cell lines utilized to study mechanisms in normal placental development as well as those responsible for tumor progression. We discuss the pathobiology of hyper-invasive placentas and show thattrophoblastic neoplasias are a unique and heterogeneous class of tumors. We delve into the questions as to why metastasis from other organs rarely occurs at the placental site and whether pregnancy makes the mother more or less vulnerable to cancer-related morbidity/mortality. We attempt to compare trophoblast stem cells and cancer stem cells. Finally, we leave the readers with some thoughts as foods of future investigations.
Topics: Choriocarcinoma; Female; Humans; Neoplasms; Placenta; Placentation; Pregnancy; Uterine Neoplasms
PubMed: 33958236
DOI: 10.1016/j.placenta.2021.03.003 -
Seminars in Reproductive Medicine Jan 2016Trophoblast cells of the murine placenta are derived from the trophectoderm (TE) cells of the preimplantation embryo. Establishment of the TE cell lineage is the result... (Review)
Review
Trophoblast cells of the murine placenta are derived from the trophectoderm (TE) cells of the preimplantation embryo. Establishment of the TE cell lineage is the result of a cell segregation event early in blastomere division. Models of cell lineage segregation suggest it is driven by the internalization of spatial information which induce or inhibit specific signaling pathways. Once segregated, TE cells undergo a differentiation event, resulting in both proliferative and terminally differentiated trophoblast cells. Thus, the development of a healthy, functional placenta relies on the well-choreographed events of trophoblast segregation, proliferation and differentiation. The pre and peri-implantation events that contribute to the development of the four main types of placental trophoblasts are the subject of this review. Identifying the components and promotors of trophoblast development will lead to a more comprehensive understanding of diseases associated with abnormal placentation and recurrent pregnancy loss.
Topics: Animals; Blastocyst; Cell Differentiation; Cell Separation; Embryonic Development; Female; Humans; Mice; Placenta; Placenta Diseases; Placentation; Pregnancy; Pregnancy Outcome; Trophoblasts
PubMed: 26757060
DOI: 10.1055/s-0035-1570025 -
International Journal of Molecular... Nov 2019Human pregnancy relies on hemochorial placentation, including implantation of the blastocyst and deep invasion of fetal trophoblast cells into maternal uterine blood... (Review)
Review
Human pregnancy relies on hemochorial placentation, including implantation of the blastocyst and deep invasion of fetal trophoblast cells into maternal uterine blood vessels, enabling direct contact of maternal blood with placental villi. Hemochorial placentation requires fast and reliable hemostasis to guarantee survival of the mother, but also for the neonates. During human pregnancy, maternal platelet count decreases gradually from first, to second, and third trimester. In addition to hemodilution, accelerated platelet sequestration and consumption in the placental circulation may contribute to a decline of platelet count throughout gestation. Local stasis, turbulences, or damage of the syncytiotrophoblast layer can activate maternal platelets within the placental intervillous space and result in formation of fibrin-type fibrinoid. Perivillous fibrinoid is a regular constituent of the normal placenta which is considered to be an important regulator of intervillous hemodynamics, as well as having a role in shaping the developing villous trees. However, exaggerated activation of platelets at the maternal-fetal interface can provoke inflammasome activation in the placental trophoblast, and enhance formation of circulating platelet-monocyte aggregates, resulting in sterile inflammation of the placenta and a systemic inflammatory response in the mother. Hence, the degree of activation determines whether maternal platelets are a friend or foe of the human placenta. Exaggerated activation of maternal platelets can either directly cause or propagate the disease process in placenta-associated pregnancy pathologies, such as preeclampsia.
Topics: Blood Platelets; Female; Hemostasis; Humans; Placenta; Placentation; Pre-Eclampsia; Pregnancy
PubMed: 31718032
DOI: 10.3390/ijms20225639 -
International Journal of Molecular... Jun 2020With establishment of uteroplacental blood flow, the perfused fetal chorionic tissue has to deal with fluid shear stress that is produced by hemodynamic forces across... (Review)
Review
With establishment of uteroplacental blood flow, the perfused fetal chorionic tissue has to deal with fluid shear stress that is produced by hemodynamic forces across different trophoblast subtypes. Amongst many other cell types, trophoblasts are able to sense fluid shear stress through mechanotransduction. Failure in the adaption of trophoblasts to fluid shear stress is suggested to contribute to pregnancy disorders. Thus, in the past twenty years, a significant body of work has been devoted to human- and animal-derived trophoblast culture under microfluidic conditions, using a rather broad range of different fluid shear stress values as well as various different flow systems, ranging from commercially 2D to customized 3D flow culture systems. The great variations in the experimental setup reflect the general heterogeneity in blood flow through different segments of the uteroplacental circulation. While fluid shear stress is moderate in invaded uterine spiral arteries, it drastically declines after entrance of the maternal blood into the wide cavity of the intervillous space. Here, we provide an overview of the increasing body of evidence that substantiates an important influence of maternal blood flow on several aspects of trophoblast physiology, including cellular turnover and differentiation, trophoblast metabolism, as well as endocrine activity, and motility. Future trends in trophoblast flow culture will incorporate the physiological low oxygen conditions in human placental tissue and pulsatile blood flow in the experimental setup. Investigation of trophoblast mechanotransduction and development of mechanosome modulators will be another intriguing future direction.
Topics: Cell Culture Techniques; Cell Differentiation; Cell Movement; Female; Humans; Placental Circulation; Placentation; Pregnancy; Trophoblasts
PubMed: 32630006
DOI: 10.3390/ijms21134666