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Clinical Microbiology Reviews Jun 2024SUMMARYViral infections during pregnancy are associated with significant adverse perinatal and fetal outcomes. Pregnancy is a unique immunologic and physiologic state,... (Review)
Review
SUMMARYViral infections during pregnancy are associated with significant adverse perinatal and fetal outcomes. Pregnancy is a unique immunologic and physiologic state, which can influence control of virus replication, severity of disease, and vertical transmission. The placenta is the organ of the maternal-fetal interface and provides defense against microbial infection while supporting the semi-allogeneic fetus via tolerogenic immune responses. Some viruses, such as cytomegalovirus, Zika virus, and rubella virus, can breach these defenses, directly infecting the fetus and having long-lasting consequences. Even without direct placental infection, other viruses, including respiratory viruses like influenza viruses and severe acute respiratory syndrome coronavirus 2, still cause placental damage and inflammation. Concentrations of progesterone and estrogens rise during pregnancy and contribute to immunological adaptations, placentation, and placental development and play a pivotal role in creating a tolerogenic environment at the maternal-fetal interface. Animal models, including mice, nonhuman primates, rabbits, and guinea pigs, are instrumental for mechanistic insights into the pathogenesis of viral infections during pregnancy and identification of targetable treatments to improve health outcomes of pregnant individuals and offspring.
Topics: Pregnancy; Female; Humans; Pregnancy Complications, Infectious; Animals; Virus Diseases; Placenta; Infectious Disease Transmission, Vertical; Disease Models, Animal
PubMed: 38421182
DOI: 10.1128/cmr.00073-23 -
Frontiers in Immunology 2024Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone with many physiological and biological roles. Melatonin is an antioxidant, anti-inflammatory, free... (Review)
Review
Melatonin (N-acetyl-5-methoxytryptamine) is an indolamine hormone with many physiological and biological roles. Melatonin is an antioxidant, anti-inflammatory, free radical scavenger, circadian rhythm regulator, and sleep hormone. However, its most popular role is the ability to regulate sleep through the circadian rhythm. Interestingly, recent studies have shown that melatonin is an important and essential hormone during pregnancy, specifically in the placenta. This is primarily due to the placenta's ability to synthesize its own melatonin rather than depending on the pineal gland. During pregnancy, melatonin acts as an antioxidant and anti-inflammatory, which is necessary to ensure a stable environment for both the mother and the fetus. It is an essential antioxidant in the placenta because it reduces oxidative stress by constantly scavenging for free radicals, i.e., maintain the placenta's integrity. In a healthy pregnancy, the maternal immune system is constantly altered to accommodate the needs of the growing fetus, and melatonin acts as a key anti-inflammatory by regulating immune homeostasis during early and late gestation. This literature review aims to identify and summarize melatonin's role as a powerful antioxidant and anti-inflammatory that reduces oxidative stress and inflammation to maintain a favorable homeostatic environment in the placenta throughout gestation.
Topics: Pregnancy; Female; Humans; Melatonin; Antioxidants; Placenta; Free Radical Scavengers; Anti-Inflammatory Agents
PubMed: 38361952
DOI: 10.3389/fimmu.2024.1339304 -
Nutrients Aug 2023Placental development is a tightly controlled event, in which cell expansion from the trophectoderm occurs in a spatiotemporal manner. Proper trophoblast differentiation... (Review)
Review
Placental development is a tightly controlled event, in which cell expansion from the trophectoderm occurs in a spatiotemporal manner. Proper trophoblast differentiation is crucial to the vitality of this gestational organ. Obstructions to its development can lead to pregnancy complications, such as preeclampsia, fetal growth restriction, and preterm birth, posing severe health risks to both the mother and offspring. Currently, the only known treatment strategy for these complications is delivery, making it an important area of research. The aim of this review was to summarize the known information on the development and mechanistic regulation of trophoblast differentiation and highlight the similarities in these processes between the human and mouse placenta. Additionally, the known biomarkers for each cell type were compiled to aid in the analysis of sequencing technologies.
Topics: Infant, Newborn; Pregnancy; Humans; Animals; Mice; Female; Trophoblasts; Placenta; Premature Birth; Cell Differentiation; Pre-Eclampsia
PubMed: 37630754
DOI: 10.3390/nu15163564 -
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 -
Placenta Oct 2023The placenta provides the vital nutrients and removal of waste products required for fetal growth and development. Understanding and quantifying the differences in... (Review)
Review
The placenta provides the vital nutrients and removal of waste products required for fetal growth and development. Understanding and quantifying the differences in structure and function between a normally functioning placenta compared to an abnormal placenta is vital to provide insights into the aetiology and treatment options for fetal growth restriction and other placental disorders. Computational modelling of blood flow in the placenta allows a new understanding of the placental circulation to be obtained. This structured review discusses multiple recent methods for placental vascular model development including analysis of the appearance of the placental vasculature and how placental haemodynamics may be simulated at multiple length scales.
Topics: Pregnancy; Female; Humans; Placenta; Placental Circulation; Fetal Development; Hemodynamics; Computer Simulation; Placenta Diseases
PubMed: 37639951
DOI: 10.1016/j.placenta.2023.08.068 -
International Journal of Medical... 2023Recurrent miscarriage (RM) is a pregnancy complication associated with dysregulation of the maternal-fetal interface. We aimed to identify dysfunctional interactions...
Recurrent miscarriage (RM) is a pregnancy complication associated with dysregulation of the maternal-fetal interface. We aimed to identify dysfunctional interactions between trophoblast cells and decidual immune cells in RM. We downloaded single-cell RNA sequencing (scRNA-seq) datasets (GSE214607) from the Gene Expression Omnibus (GEO) datasets for further analysis using the R software. The data comprised of paired placental and decidual tissues, including those from patients diagnosed with RM and matched healthy controls. A total of 22976 cells were identified in 11 cell types, including trophoblasts, immune cells, and other cells. We divided trophoblast cells into three types and analyzed their interactions with decidual immune cells. Additionally, we re-clustered NK&T cells and macrophages, identified differentially expressed genes (DEGs), enriched their functions, and compared the cell interactions with trophoblast cells in each cell type. Our single-cell atlas of the maternal-fetal interface revealed alterations in the cellular organization of the decidua and placenta, cell type-specific transcriptome, and cell communication between immune and non-immune cells in RM, which are critical for illuminating the pathophysiology of RM.
Topics: Pregnancy; Humans; Female; Placenta; Trophoblasts; Decidua; Abortion, Habitual; Pregnancy Trimester, First
PubMed: 37575278
DOI: 10.7150/ijms.86533 -
Placenta Sep 2023Spiral artery remodeling is the process by which the uterine vessels become large bore low resistance conduits, allowing delivery of high volumes of maternal blood to... (Review)
Review
Spiral artery remodeling is the process by which the uterine vessels become large bore low resistance conduits, allowing delivery of high volumes of maternal blood to the placenta to nourish the developing fetus. Failure of this process is associated with the pathophysiology of most of the major obstetric complications, including late miscarriage, fetal growth restriction and pre-eclampsia. However, the point at which remodeling 'fails' in these pathological pregnancies is not yet clear. Spiral artery remodeling has predominantly been described in terms of its morphological features, however we are starting to understand more about the cellular and molecular triggers of the different aspects of this process. This review will discuss the current state of knowledge of spiral artery remodeling, in particular the processes involved in loss of the vascular smooth muscle cells, and consider where in the process defects would lead to a pathological pregnancy.
Topics: Pregnancy; Female; Humans; Trophoblasts; Placenta; Uterus; Arteries; Abortion, Spontaneous; Pre-Eclampsia; Vascular Remodeling; Decidua
PubMed: 37308346
DOI: 10.1016/j.placenta.2023.05.013 -
Reproduction (Cambridge, England) Dec 2023Preeclampsia (PE) is a severe complication that leads to major maternal and fetal mortality and morbidity, and one of its causes is extravillous trophoblast (EVT)...
IN BRIEF
Preeclampsia (PE) is a severe complication that leads to major maternal and fetal mortality and morbidity, and one of its causes is extravillous trophoblast (EVT) dysfunction. This study revealed the role of CD74 in the invasion and proliferation of EVTs.
ABSTRACT
PE is a severe hypertensive disorder during pregnancy, and one of its causes is the dysfunction of EVTs. In this study, we analyzed single-cell RNA sequencing (scRNA-seq) data of placentas from PE patients and the sirtuin 1 (SIRT1) heterozygous knockout mouse model, which exhibited typical PE-like symptoms. We identified 134 differentially expressed genes (DEGs) with similar trends in EVTs of PE patients and in parietal trophoblast giant cells (P-TGCs) of Sirt1-/- (HO) placentas from Sirt1+/- (HE) pregnant mice. Interestingly, Kyoto Encyclopedia of Genes and Genomes analysis showed that 134 overlapping genes were related to the MAPK signaling pathway. We validated several DEGs using immunofluorescence at the protein level. Finally, we selected CD74 for further experiments, which showed a decrease in EVTs of PE patients and in P-TGCs of Sirt1-/- placentas from Sirt1+/- pregnant mice. Additionally, cell proliferation assays and transwell assays showed that the proliferation and invasion abilities were decreased in CD74 knockdown HTR8/SVneo cells using lentivirus transfection, which can be improved by adding the SIRT1 agonist SRT1720 or metformin, an agonist of the MAPK signaling pathway. Importantly, the expression of CD74 can be positively regulated by SIRT1. These data suggest that CD74 plays an important protective role in the pathogenesis of preeclampsia by regulating the MAPK signaling pathway, which can be regulated by SIRT1.
Topics: Pregnancy; Female; Humans; Mice; Animals; Trophoblasts; Sirtuin 1; Pre-Eclampsia; Placenta; Cell Proliferation; Cell Movement
PubMed: 37796743
DOI: 10.1530/REP-23-0202 -
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 -
BMC Pregnancy and Childbirth Aug 2023A previous study investigated the effect of adenomyosis on perinatal outcomes. Some studies have reported varying effect of adenomyosis on pregnancy outcomes in some...
BACKGROUND
A previous study investigated the effect of adenomyosis on perinatal outcomes. Some studies have reported varying effect of adenomyosis on pregnancy outcomes in some patients and dependence on the degree and subtype of uterine lesions. To elucidate the impact of adenomyosis on perinatal outcomes.
METHODS
This large-scale cohort study used the perinatal registry database of the Japan Society of Obstetrics and Gynecology. A dataset of 203,745 mothers who gave birth between January 2020 and December 2020 in Japan was included in the study. The participants were divided into two groups based on the presence or absence of adenomyosis. Information regarding the use of fertility treatment, delivery, obstetric complications, maternal treatments, infant, fetal appendages, obstetric history, underlying diseases, infectious diseases, use of drugs, and maternal and infant death were compared between the groups.
RESULTS
In total, 1,204 participants had a history of adenomyosis and 151,105 did not. The adenomyosis group had higher rates of uterine rupture (0.2% vs. 0.01%, P = 0.02) and placenta accreta (2.0% vs. 0.5%, P < 0.001) than the non-adenomyosis group. A history of adenomyosis (odds ratio: 2.26; 95% confidence interval: 1.43-3.27; P < 0.001), uterine rupture (odds ratio: 3.45; 95% confidence interval: 0.89-19.65; P = 0.02), placental abruption (odds ratio: 2.11; 95% confidence interval: 1.27-3.31; P < 0.01), and fetal growth restriction (odds ratio: 2.66; 95% confidence interval: 2.00-3.48; P < 0.01) were independent risk factors for placenta accreta.
CONCLUSION
Adenomyosis in pregnancies is associated with an increased risk of placenta accreta, uterine rupture, placental abruption, and fetal growth restriction.
TRIAL REGISTRATION
Institutional Review Board of Tottori University Hospital (IRB no. 21A244).
Topics: Pregnancy; Female; Humans; Cohort Studies; Abruptio Placentae; Uterine Rupture; Placenta Accreta; Fetal Growth Retardation; Retrospective Studies; Placenta; Adenomyosis
PubMed: 37568120
DOI: 10.1186/s12884-023-05895-w