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Developmental Cell Dec 2023The placenta becomes one of the most diversified organs during placental mammal radiation. The main in vitro model for studying mouse trophoblast development is the 2D...
The placenta becomes one of the most diversified organs during placental mammal radiation. The main in vitro model for studying mouse trophoblast development is the 2D differentiation model of trophoblast stem cells, which is highly skewed to certain lineages and thus hampers systematic screens. Here, we established culture conditions for the establishment, maintenance, and differentiation of murine trophoblast organoids. Murine trophoblast organoids under the maintenance condition contain stem cell-like populations, whereas differentiated organoids possess various trophoblasts resembling placental ones in vivo. Ablation of Nubpl or Gcm1 in trophoblast organoids recapitulated their deficiency phenotypes in vivo, suggesting that those organoids are valid in vitro models for trophoblast development. Importantly, we performed an efficient CRISPR-Cas9 screening in mouse trophoblast organoids using a focused sgRNA (single guide RNA) library targeting G protein-coupled receptors. Together, our results establish an organoid model to investigate mouse trophoblast development and a practicable approach to performing forward screening in trophoblast lineages.
Topics: Pregnancy; Female; Mice; Animals; Placenta; CRISPR-Cas Systems; RNA, Guide, CRISPR-Cas Systems; Trophoblasts; Cell Differentiation; Organoids; Mammals
PubMed: 38056451
DOI: 10.1016/j.devcel.2023.11.007 -
Reproductive Sciences (Thousand Oaks,... Jul 2023Ferroptosis is a recently identified form of programmed cell death which is different from apoptosis, pyroptosis, necrosis, and autophagy. It is uniquely defined by... (Review)
Review
Ferroptosis is a recently identified form of programmed cell death which is different from apoptosis, pyroptosis, necrosis, and autophagy. It is uniquely defined by redox-active iron-dependent hydroxy-peroxidation of polyunsaturated fatty acid (PUFA)-containing phospholipids and a loss of lipid peroxidation repair capacity. Ferroptosis has recently been implicated in multiple human diseases, such as tumors, ischemia-reperfusion injury, acute kidney injury, neurological diseases, and asthma among others. Intriguingly, ferroptosis is associated with placental physiology and trophoblast injury. Circumstances such as accumulation of lipid reactive oxygen species (ROS) due to hypoxia-reperfusion and anoxia-reoxygenation of trophoblast during placental development, the abundance of trophoblastic iron and PUFA, physiological uterine contractions, or pathological placental bed perfusion, cause placental trophoblasts' susceptibility to ferroptosis. Ferroptosis of trophoblast can cause placental dysfunction, which may be involved in the occurrence and development of placenta-related diseases such as gestational diabetes mellitus, preeclampsia, fetal growth restriction, preterm birth, and abortion. The regulatory mechanisms of trophoblastic ferroptosis still need to be explored further. Here, we summarize the latest progress in trophoblastic ferroptosis research on placental-related diseases, provide references for further understanding of its pathogenesis, and propose new strategies for the prevention and treatment of placental-related diseases.
Topics: Infant, Newborn; Pregnancy; Female; Humans; Placenta; Ferroptosis; Premature Birth; Apoptosis; Lipid Peroxidation; Iron; Placenta Diseases; Hypoxia
PubMed: 36930425
DOI: 10.1007/s43032-023-01193-0 -
Frontiers in Endocrinology 2023Embryo implantation and placentation play pivotal roles in pregnancy by facilitating crucial maternal-fetal interactions. These dynamic processes involve significant... (Review)
Review
Embryo implantation and placentation play pivotal roles in pregnancy by facilitating crucial maternal-fetal interactions. These dynamic processes involve significant alterations in gene expression profiles within the endometrium and trophoblast lineages. Epigenetics regulatory mechanisms, such as DNA methylation, histone modification, chromatin remodeling, and microRNA expression, act as regulatory switches to modulate gene activity, and have been implicated in establishing a successful pregnancy. Exploring the alterations in these epigenetic modifications can provide valuable insights for the development of therapeutic strategies targeting complications related to pregnancy. However, our current understanding of these mechanisms during key gestational stages remains incomplete. This review focuses on recent advancements in the study of histone modifications during embryo implantation and placentation, while also highlighting future research directions in this field.
Topics: Female; Animals; Mice; Pregnancy; Histone Code; Placentation; Protein Processing, Post-Translational; Chromatin Assembly and Disassembly; Embryo Implantation; Disease Models, Animal
PubMed: 37600694
DOI: 10.3389/fendo.2023.1229862 -
Biology of Reproduction Sep 2023During pregnancy, cell senescence at the maternal-fetal interface is required for maternal well-being, placental development, and fetal growth. However, recent reports... (Review)
Review
During pregnancy, cell senescence at the maternal-fetal interface is required for maternal well-being, placental development, and fetal growth. However, recent reports have shown that aberrant cell senescence is associated with multiple pregnancy-associated abnormalities, such as preeclampsia, fetal growth restrictions, recurrent pregnancy loss, and preterm birth. Therefore, the role and impact of cell senescence during pregnancy requires further comprehension. In this review, we discuss the principal role of cell senescence at the maternal-fetal interface, emphasizing its "bright side" during decidualization, placentation, and parturition. In addition, we highlight the impact of its deregulation and how this "dark side" promotes pregnancy-associated abnormalities. Furthermore, we discuss novel and less invasive therapeutic practices associated with the modulation of cell senescence during pregnancy.
Topics: Pregnancy; Female; Infant, Newborn; Humans; Placenta; Premature Birth; Parturition; Placentation; Cellular Senescence
PubMed: 37402700
DOI: 10.1093/biolre/ioad071 -
International Journal of Molecular... Feb 2024Pre-eclampsia is a serious complication of pregnancy characterized by a state of multiorgan hypertensive disorders, with or without proteinuria and possible multiorgan... (Review)
Review
Pre-eclampsia is a serious complication of pregnancy characterized by a state of multiorgan hypertensive disorders, with or without proteinuria and possible multiorgan dysfunction. Chronic kidney disease is an established risk factor for the development of pre-eclampsia, as angiogenic homeostasis is altered and the maternal circulation is already hypertensive. Facing pre-eclampsia in the context of chronic kidney disease is a challenging emergency for both the mother and the fetus. The clinical features and the management of this multi-organ disorder are clearly defined in the modern literature but the underlying pathophysiologic mechanisms remain not fully elucidated. Understanding the pathophysiology that mediates the onset of pre-eclampsia itself and in synergy with chronic kidney disease is fundamental for developing prompt prevention strategies, treatment planning, and patient counseling. This review aims to summarize the main molecular mechanisms involved in the process of pre-eclampsia, with a particular focus on the role of the kidneys and hormonal pathways related to renal function in normal pregnancy and pre-eclamptic syndromes.
Topics: Pregnancy; Female; Humans; Placenta; Pre-Eclampsia; Kidney; Hypertension; Renal Insufficiency, Chronic
PubMed: 38473987
DOI: 10.3390/ijms25052741 -
Journal of Human Hypertension Aug 2023Higher blood pressure prior to pregnancy is associated with increased risk of placental abruption, hypertension and preeclampsia, preterm delivery and fetal growth... (Review)
Review
Higher blood pressure prior to pregnancy is associated with increased risk of placental abruption, hypertension and preeclampsia, preterm delivery and fetal growth restriction. These conditions are jointly termed placental syndromes as they are characterised by impaired placentation and early placental vascularization. Placental syndromes are associated with an increased maternal risk of progression to hypertension and cardiovascular disease (CVD) in later life. Women affected by both a clinical placental syndrome and with evidence of placental maternal vascular malperfusion (MVM) have a particularly high risk of hypertension and CVD. Yet whether placental impairment and clinical syndromes are causes or consequences of higher blood pressure in women remains unclear. In this review, we address the relationship between blood pressure and maternal health in pregnancy. We conclude that there is a pressing need for studies with a range of detailed measures of cardiac and vascular structure and function taken before, during and after pregnancy to solve the 'chicken and egg' puzzle of women's blood pressure and pregnancy health, and to inform effective precision medicine prevention and treatment of both placental syndromes and chronic hypertension in women.
Topics: Pregnancy; Female; Humans; Placenta; Syndrome; Hypertension; Pre-Eclampsia; Cardiovascular Diseases; Placentation
PubMed: 36702879
DOI: 10.1038/s41371-023-00802-4 -
Development (Cambridge, England) Oct 2023Compelling epidemiological and animal experimental data demonstrate that cardiometabolic and neuropsychiatric diseases originate in a suboptimal intrauterine... (Review)
Review
Compelling epidemiological and animal experimental data demonstrate that cardiometabolic and neuropsychiatric diseases originate in a suboptimal intrauterine environment. Here, we review evidence suggesting that altered placental function may, at least in part, mediate the link between the maternal environment and changes in fetal growth and development. Emerging evidence indicates that the placenta controls the development and function of several fetal tissues through nutrient sensing, modulation of trophoblast nutrient transporters and by altering the number and cargo of released extracellular vesicles. In this Review, we discuss the development and functions of the maternal-placental-fetal interface (in humans and mice) and how cross-talk between these compartments may be a mechanism for in utero programming, focusing on mechanistic target of rapamycin (mTOR), adiponectin and O-GlcNac transferase (OGT) signaling. We also discuss how maternal diet and stress influences fetal development and metabolism and how fetal growth restriction can result in susceptibility to developing chronic disease later in life. Finally, we speculate how interventions targeting placental function may offer unprecedented opportunities to prevent cardiometabolic disease in future generations.
Topics: Pregnancy; Female; Humans; Mice; Animals; Placenta; Fetal Development; Trophoblasts; Signal Transduction; Fetal Growth Retardation
PubMed: 37831056
DOI: 10.1242/dev.202088 -
Frontiers in Endocrinology 2023The maternal-fetal interface is defined as the interface between maternal tissue and sections of the fetus in close contact. RNA methylation modifications are the most... (Review)
Review
The maternal-fetal interface is defined as the interface between maternal tissue and sections of the fetus in close contact. RNA methylation modifications are the most frequent kind of RNA alterations. It is effective throughout both normal and pathological implantation and placentation during pregnancy. By influencing early embryo development, embryo implantation, endometrium receptivity, immune microenvironment, as well as some implantation and placentation-related disorders like miscarriage and preeclampsia, it is essential for the establishment of the maternal-fetal interface. Our review focuses on the role of dynamic RNA methylation at the maternal-fetal interface, which has received little attention thus far. It has given the mechanistic underpinnings for both normal and abnormal implantation and placentation and could eventually provide an entirely novel approach to treating related complications.
Topics: Female; Pregnancy; Humans; Methylation; Placentation; Embryo Implantation; Embryonic Development; RNA
PubMed: 37720526
DOI: 10.3389/fendo.2023.1205408 -
Biomolecules Oct 2023Endogenous retroviruses (ERVs) are retrovirus-like sequences that were previously integrated into the host genome. Although most ERVs are inactivated by mutations,... (Review)
Review
Endogenous retroviruses (ERVs) are retrovirus-like sequences that were previously integrated into the host genome. Although most ERVs are inactivated by mutations, deletions, or epigenetic regulation, some remain transcriptionally active and impact host physiology. Several ERV-encoded proteins, such as Syncytins and Suppressyn, contribute to placenta acquisition, a crucial adaptation in mammals that protects the fetus from external threats and other risks while enabling the maternal supply of oxygen, nutrients, and antibodies. In primates, Syncytin-1 and Syncytin-2 facilitate cell-cell fusion for placental formation. Suppressyn is the first ERV-derived protein that inhibits cell fusion by binding to ASCT2, the receptor for Syncytin-1. Furthermore, Syncytin-2 likely inserted into the genome of the common ancestor of Anthropoidea, whereas Syncytin-1 and Suppressyn likely inserted into the ancestor of catarrhines; however, they were inactivated in some lineages, suggesting that multiple exaptation events had occurred. This review discusses the role of ERV-encoded proteins, particularly Syncytins and Suppressyn, in placental development and function, focusing on the integration of ERVs into the host genome and their contribution to the genetic mechanisms underlying placentogenesis. This review provides valuable insights into the molecular and genetic aspects of placentation, potentially shedding light on broader evolutionary and physiological processes in mammals.
Topics: Animals; Pregnancy; Female; Placenta; Endogenous Retroviruses; Epigenesis, Genetic; Placentation; Gene Products, env; Mammals
PubMed: 37892164
DOI: 10.3390/biom13101482 -
American Journal of Reproductive... May 2024Preeclampsia, poses significant risks to both maternal and fetal well-being. Exosomes released by the placenta play a crucial role in intercellular communication and are... (Review)
Review
Preeclampsia, poses significant risks to both maternal and fetal well-being. Exosomes released by the placenta play a crucial role in intercellular communication and are recognized as potential carriers of essential information for placental development. These exosomes transport a payload of proteins, nucleic acids, and lipids that mirror the placental microenvironment. This review delves into the functional roles of placental exosomes and its contents shedding light on their involvement in vascular regulation and immune modulation in normal pregnancy. Discernible changes are reported in the composition and quantity of placental exosome contents in pregnancies affected by preeclampsia. The exosomes from preeclamptic mothers affect vascularization and fetal kidney development. The discussion also explores the implications of utilizing placental exosomes as biomarkers and the prospects of translating these findings into clinical applications. In conclusion, placental exosomes hold promise as a valuable avenue for deciphering the complexities of preeclampsia, providing crucial diagnostic and prognostic insights. As the field progresses, a more profound comprehension of the distinct molecular signatures carried by placental exosomes may open doors to innovative strategies for managing and offering personalized care to pregnancies affected by preeclampsia.
Topics: Humans; Pregnancy; Pre-Eclampsia; Exosomes; Female; Placenta; Biomarkers; Animals; Cell Communication
PubMed: 38716824
DOI: 10.1111/aji.13857