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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 -
Placenta Aug 2022Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been implicated in the clinical pathology of... (Review)
Review
Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) virus has been implicated in the clinical pathology of multiple organs and organ systems. Due to the novelty of the disease, there is a need to review emerging literature to understand the profile of SARS-CoV-2 in the placenta. This review sought to evaluate the literature on the mediators, mechanism of entry, pathogenesis, detection, and pathology of SARS-CoV-2 in the placenta. Systematic literature searches found 96 eligible studies. Our review revealed that SARS-CoV-2 canonical mediators, angiotensin-converting enzyme-2 (ACE2), and transmembrane serine protease-2 (TMPRSS2) are variably expressed in various placenta compartments, including the villous cytotrophoblasts, syncytiotrophoblasts (STBs), and extravillous trophoblasts (EVTs) throughout pregnancy. Placental SARS-CoV-2 and coronavirus-associated receptors and factors (SCARFs), including basigin (BSG/CD147), dipeptidyl peptidase-4 (DPP4/CD26), cathepsin B/L (CTL B/L), furin, interferon-induced transmembrane protein (IFITM1-3), and lymphocyte antigen 6E (LY6E) may increase or reduce the permissiveness of the placenta to SARS-CoV-2. EVTs express genes that code for proteins that may drive viral pathogenesis in the placenta. Viral RNA, proteins, and particles were detected primarily in the STBs by in situ hybridization, immunohistochemistry, electron microscopy, and polymerase chain reaction. Placental pathology in SARS-CoV-2-infected placentas included maternal and fetal vascular malperfusion and a generally nonspecific inflammatory-immune response. The localization of SARS-CoV-2 receptors, proteases, and genes involved in coding proteins that drive viral pathogenesis in the placenta predisposes the placenta to SARS-CoV-2 infection variably in all pregnancy trimesters, with antecedent placental pathology. There is a need for further studies to explicate the mechanism of entry and pathogenesis of SARS-CoV-2 in the placenta.
Topics: COVID-19; Female; Humans; Placenta; Pregnancy; Pregnancy Complications, Infectious; SARS-CoV-2; Trophoblasts
PubMed: 35872511
DOI: 10.1016/j.placenta.2022.07.007 -
Revista Brasileira de Ginecologia E... Jun 2021Placental pathophysiology in SARS-CoV-2 infection can help researchers understand more about the infection and its impact on the maternal/neonatal outcomes. This brief... (Review)
Review
Placental pathophysiology in SARS-CoV-2 infection can help researchers understand more about the infection and its impact on the maternal/neonatal outcomes. This brief review provides an overview about some aspects of the placental pathology in SARS-CoV-2 infection. In total, 11 papers were included. The current literature suggests that there are no specific histopathological characteristics in the placenta related to SARS-CoV-2 infection, but placentas from infected women are more likely to show findings of maternal and/or fetal malperfusion. The most common findings in placentas from infected women were fibrin deposition and intense recruitment of inflammatory infiltrates. The transplacental transmission of this virus is unlikely to occur, probably due to low expression of the receptor for SARS-CoV-2 in placental cell types. Further studies are needed to improve our knowledge about the interaction between the virus and the mother-fetus dyad and the impact on maternal and neonatal/fetal outcomes.
Topics: COVID-19; Female; Humans; Infectious Disease Transmission, Vertical; Placenta; Pregnancy; Pregnancy Complications, Infectious
PubMed: 34077991
DOI: 10.1055/s-0041-1730291 -
PloS One 2022Trophoblast inclusions-cross sections of abnormal trophoblast bilayer infoldings-have previously been associated with aneuploidy, placenta accreta, and prematurity. This...
OBJECTIVE
Trophoblast inclusions-cross sections of abnormal trophoblast bilayer infoldings-have previously been associated with aneuploidy, placenta accreta, and prematurity. This study was conducted to establish the relationship between trophoblast inclusions and a range of placental, pregnancy, and birth outcomes in a patient population with high smoking and alcohol exposure. Specifically, we sought to evaluate the association between the presence of trophoblast inclusions and 1) three primary birth outcomes: full-term birth, preterm birth, and stillbirth; 2) gestational age at delivery; and 3) specific placental pathologies.
METHODS
Two slides containing chorionic villi were evaluated from 589 placentas that were collected from Stellenbosch University in Cape Town, South Africa as part of the prospective, multicenter cohort Safe Passage Study of the Prenatal Alcohol and SIDS and Stillbirth Network. The subsample included 307 full-term live births, 212 preterm live births, and 70 stillbirths.
RESULTS
We found that the odds of identifying at least one trophoblast inclusion across two slides of chorionic villi was significantly higher for placentas from preterm compared to term liveborn deliveries (OR = 1.74; 95% CI: 1.22, 2.49, p = 0.002), with an even greater odds ratio for placentas from stillborn compared to term liveborn deliveries (OR = 4.95; 95% CI: 2.78, 8.80, p < 0.001). Gestational age at delivery was inversely associated with trophoblast inclusion frequency. Trophoblast inclusions were significantly associated with small for gestational age birthweight, induction of labor, villous edema, placental infarction, and inflammation of the chorionic plate.
CONCLUSIONS
The novel associations that we report warrant further investigation in order to understand the complex network of biological mechanisms through which the factors that lead to trophoblast inclusions may influence or reflect the trajectory and health of a pregnancy. Ultimately, this line of research may provide critical insights that could inform both clinical and research applications.
Topics: Female; Gestational Age; Humans; Infant, Newborn; Placenta; Pregnancy; Pregnancy Complications; Premature Birth; Prospective Studies; South Africa; Stillbirth; Trophoblasts
PubMed: 35231069
DOI: 10.1371/journal.pone.0264733 -
Human Immunology May 2021Cytotrophoblasts differentiate in two directions during early placentation: syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). STBs face maternal immune... (Review)
Review
Cytotrophoblasts differentiate in two directions during early placentation: syncytiotrophoblasts (STBs) and extravillous trophoblasts (EVTs). STBs face maternal immune cells in placentas, and EVTs, which invade the decidua and uterine myometrium, face the cells in the uterus. This situation, in which trophoblasts come into contact with maternal immune cells, is known as the maternal-fetal interface. Despite fetuses and fetus-derived trophoblast cells being of the semi-allogeneic conceptus, fetuses and placentas are not rejected by the maternal immune system because of maternal-fetal tolerance. The acquired tolerance develops during normal placentation, resulting in normal fetal development in humans. In this review, we introduce placental development from the viewpoint of molecular biology. In addition, we discuss how the disruption of placental development could lead to complications in pregnancy, such as hypertensive disorder of pregnancy, fetal growth restriction, or miscarriage.
Topics: Animals; Autophagy; Decidua; Female; Giant Cells; Histocompatibility, Maternal-Fetal; Humans; Immune Tolerance; Placenta; Pregnancy; T-Lymphocytes, Regulatory
PubMed: 33581928
DOI: 10.1016/j.humimm.2021.01.012 -
Reproduction (Cambridge, England) Dec 2020Human placenta is a complex and heterogeneous organ interfacing between the mother and the fetus that supports fetal development. Alterations to placental structural... (Review)
Review
Human placenta is a complex and heterogeneous organ interfacing between the mother and the fetus that supports fetal development. Alterations to placental structural components are associated with various pregnancy complications. To reveal the heterogeneity among various placenta cell types in normal and diseased placentas, as well as elucidate molecular interactions within a population of placental cells, a new genomics technology called single cell RNA-seq (or scRNA-seq) has been employed in the last couple of years. Here we review the principles of scRNA-seq technology, and summarize the recent human placenta studies at scRNA-seq level across gestational ages as well as in pregnancy complications, such as preterm birth and preeclampsia. We list the computational analysis platforms and resources available for the public use. Lastly, we discuss the future areas of interest for placenta single cell studies, as well as the data analytics needed to accomplish them.
Topics: Female; Fetal Development; Gene Expression Profiling; Gene Expression Regulation, Developmental; Gestational Age; Humans; Placenta; Pregnancy; Pregnancy Complications; Single-Cell Analysis
PubMed: 33112783
DOI: 10.1530/REP-20-0231 -
Placenta Jan 2022Maternal anti-SARS-CoV-2 Spike antibodies can cross the placenta during pregnancy, and neonates born to infected mothers have acquired antibodies at birth. Few studies...
INTRODUCTION
Maternal anti-SARS-CoV-2 Spike antibodies can cross the placenta during pregnancy, and neonates born to infected mothers have acquired antibodies at birth. Few studies reported data on the histopathological changes of the placenta during infection and placental infection. SARS-CoV-2 infection may cause impaired development of the placenta, thus predisposing maternal and fetal unfavorable outcomes. The prospective study aims to evaluate the risk of vertical transmission of SARS-CoV-2 and placental passage of anti-Spike antibodies as well as the impact of clinical severity on placental structures.
METHODS
This is a prospective cohort study on 30 pregnant women infected by SARS-CoV-2 with their neonates. The demographic features and pregnancy outcomes were collected. Gross and microscopic examinations of the placentas were done. Maternal and umbilical cord sera were obtained at the time of delivery. Nasopharyngeal swabs were collected from neonates immediately after birth.
RESULTS
The concentrations of total anti-SARS-CoV-2 Spike antibodies were higher in pregnant women with moderate to severe/critical disease. The maternal total anti-SARS-CoV-2 Spike levels were correlated with those of neonatal levels. The rate of placental abnormalities is high in the mothers with severe disease, and those with positive anti-SARS-CoV-2 IgM. All neonates had negative nasopharyngeal swabs for SARS- CoV-2 infections and all placentas were negative in immunohistochemical staining for Spike protein.
DISCUSSION
The maternally derived anti-SARS-CoV-2 Spike antibody can transmit to neonates born to infected mothers regardless of gestational age. Our results indicated that the disease severity is associated with ischemic placental pathology which may result in adverse pregnancy outcomes.
Topics: Adult; Antibodies, Viral; COVID-19; Cohort Studies; Female; Fetal Blood; Humans; Immunity, Maternally-Acquired; Infant, Newborn; Infectious Disease Transmission, Vertical; Placenta; Placenta Diseases; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Outcome; Premature Birth; Prospective Studies; SARS-CoV-2; Severity of Illness Index; Spike Glycoprotein, Coronavirus
PubMed: 34768168
DOI: 10.1016/j.placenta.2021.10.012 -
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 -
Nature Apr 2021Placentas can exhibit chromosomal aberrations that are absent from the fetus. The basis of this genetic segregation, which is known as confined placental mosaicism,...
Placentas can exhibit chromosomal aberrations that are absent from the fetus. The basis of this genetic segregation, which is known as confined placental mosaicism, remains unknown. Here we investigated the phylogeny of human placental cells as reconstructed from somatic mutations, using whole-genome sequencing of 86 bulk placental samples (with a median weight of 28 mg) and of 106 microdissections of placental tissue. We found that every bulk placental sample represents a clonal expansion that is genetically distinct, and exhibits a genomic landscape akin to that of childhood cancer in terms of mutation burden and mutational imprints. To our knowledge, unlike any other healthy human tissue studied so far, the placental genomes often contained changes in copy number. We reconstructed phylogenetic relationships between tissues from the same pregnancy, which revealed that developmental bottlenecks genetically isolate placental tissues by separating trophectodermal lineages from lineages derived from the inner cell mass. Notably, there were some cases with full segregation-within a few cell divisions of the zygote-of placental lineages and lineages derived from the inner cell mass. Such early embryonic bottlenecks may enable the normalization of zygotic aneuploidy. We observed direct evidence for this in a case of mosaic trisomic rescue. Our findings reveal extensive mutagenesis in placental tissues and suggest that mosaicism is a typical feature of placental development.
Topics: Biopsy; Blastocyst Inner Cell Mass; Female; Genome, Human; Humans; Mesoderm; Mosaicism; Mutagenesis; Mutation; Mutation Rate; Placenta; Pregnancy; Trisomy; Trophoblasts; Zygote
PubMed: 33692543
DOI: 10.1038/s41586-021-03345-1 -
American Journal of Physiology.... Dec 2020Mitochondria play a key role in homeostasis and are central to one of the leading hypotheses of aging, the free radical theory. Mitochondria function as a reticulated... (Review)
Review
Mitochondria play a key role in homeostasis and are central to one of the leading hypotheses of aging, the free radical theory. Mitochondria function as a reticulated network, constantly adapting to the cellular environment through fusion (joining), biogenesis (formation of new mitochondria), and fission (separation). This adaptive response is particularly important in response to oxidative stress, cellular damage, and aging, when mitochondria are selectively removed through mitophagy, a mitochondrial equivalent of autophagy. During this complex process, mitochondria influence surrounding cell biology and organelles through the release of signaling molecules. Given that the human placenta is a unique organ having a transient and somewhat defined life span of ∼280 days, any adaption or dysfunction associated with mitochondrial physiology as a result of aging will have a dramatic impact on the health and function of both the placenta and the fetus. Additionally, a defective placenta during gestation, resulting in reduced fetal growth, has been shown to influence the development of chronic disease in later life. In this review we focus on the mitochondrial adaptions and transformations that accompany gestational length and share similarities with age-related diseases. In addition, we discuss the role of such changes in regulating placental function throughout gestation, the etiology of gestational complications, and the development of chronic diseases later in life.
Topics: Aging; Animals; Female; Humans; Mitochondria; Mitochondrial Dynamics; Mitophagy; Oxidative Stress; Placenta; Pregnancy; Signal Transduction
PubMed: 32954826
DOI: 10.1152/ajpendo.00354.2020