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International Journal of Molecular... Oct 2023The main complications causing practically 75% of all maternal deaths are severe bleeding, infections, and high blood pressure during pregnancy (preeclampsia (PE) and... (Review)
Review
The main complications causing practically 75% of all maternal deaths are severe bleeding, infections, and high blood pressure during pregnancy (preeclampsia (PE) and eclampsia). The usefulness of ncRNAs as clinical biomarkers has been explored in an extensive range of human diseases including pregnancy-related diseases such as PE. Immunological dysregulation show that the Th1/17:Th2/Treg ratio is "central and causal" to PE. However, there is evidence of the involvement of placenta-expressed miRNAs and lncRNAs in the immunological regulation of crucial processes of placenta development and function during pregnancy. Abnormal expression of these molecules is related to immune physiopathological processes that occur in PE. Therefore, this work aims to describe the importance of miRNAs and lncRNAs in immune dysregulation in PE. Interestingly, multiple ncRNAS are involved in the immune dysregulation of PE participating in type 1 immune response regulation, immune microenvironment regulation in placenta promoting inflammatory factors, trophoblast cell invasion in women with Early-Onset PE (EOPE), placental development, and angiogenesis, promotion of population of M1 and M2, proliferation, invasion, and migration of placental trophoblast cells, and promotion of invasion and autophagy through vias such as PI3K/AKT/mTOR, VEGF/VEGFR1, and TLR9/STAT3.
Topics: Humans; Pregnancy; Female; Placenta; Phosphatidylinositol 3-Kinases; Pre-Eclampsia; RNA, Long Noncoding; MicroRNAs; Trophoblasts
PubMed: 37894897
DOI: 10.3390/ijms242015215 -
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 -
International Journal of Molecular... Aug 2023Endometrial decidualization is a uterine process essential for spiral artery remodeling, embryo implantation, and trophoblast invasion. Defects in endometrial... (Review)
Review
Endometrial decidualization is a uterine process essential for spiral artery remodeling, embryo implantation, and trophoblast invasion. Defects in endometrial decidualization and spiral artery remodeling are important contributing factors in preeclampsia, a major disorder in pregnancy. Atrial natriuretic peptide (ANP) is a cardiac hormone that regulates blood volume and pressure. ANP is also generated in non-cardiac tissues, such as the uterus and placenta. In recent human genome-wide association studies, multiple loci with genes involved in natriuretic peptide signaling are associated with gestational hypertension and preeclampsia. In cellular experiments and mouse models, uterine ANP has been shown to stimulate endometrial decidualization, increase TNF-related apoptosis-inducing ligand expression and secretion, and enhance apoptosis in arterial smooth muscle cells and endothelial cells. In placental trophoblasts, ANP stimulates adenosine 5'-monophosphate-activated protein kinase and the mammalian target of rapamycin complex 1 signaling, leading to autophagy inhibition and protein kinase N3 upregulation, thereby increasing trophoblast invasiveness. ANP deficiency impairs endometrial decidualization and spiral artery remodeling, causing a preeclampsia-like phenotype in mice. These findings indicate the importance of natriuretic peptide signaling in pregnancy. This review discusses the role of ANP in uterine biology and potential implications of impaired ANP signaling in preeclampsia.
Topics: Humans; Animals; Signal Transduction; Natriuretic Peptides; Pre-Eclampsia; Uterus; Hypertension, Pregnancy-Induced; Placenta; Serine Endopeptidases
PubMed: 37569683
DOI: 10.3390/ijms241512309 -
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 -
Annual Review of Nutrition Aug 2023Pregnancy entails a large negative balance of iron, an essential micronutrient. During pregnancy, iron requirements increase substantially to support both maternal red... (Review)
Review
Pregnancy entails a large negative balance of iron, an essential micronutrient. During pregnancy, iron requirements increase substantially to support both maternal red blood cell expansion and the development of the placenta and fetus. As insufficient iron has long been linked to adverse pregnancy outcomes, universal iron supplementation is common practice before and during pregnancy. However, in high-resource countries with iron fortification of staple foods and increased red meat consumption, the effects of too much iron supplementation during pregnancy have become a concern because iron excess has also been linked to adverse pregnancy outcomes. In this review, we address physiologic iron homeostasis of the mother, placenta, and fetus and discuss perturbations in iron homeostasis that result in pathological pregnancy. As many mechanistic regulatory systems have been deduced from animal models, we also discuss the principles learned from these models and how these may apply to human pregnancy.
Topics: Animals; Pregnancy; Female; Humans; Placenta; Pregnancy Outcome; Fetus; Iron; Homeostasis
PubMed: 37253681
DOI: 10.1146/annurev-nutr-061021-030404 -
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 -
Placenta Jul 2023The impact of the COVID-19 infection, caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during the pandemic has been considerably more severe in... (Review)
Review
The impact of the COVID-19 infection, caused by Severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), during the pandemic has been considerably more severe in pregnant women than non-pregnant women. Therefore, a review detailing the morphological alterations and physiological changes associated with COVID-19 during pregnancy and the effect that these changes have on the feto-placental unit is of high priority. This knowledge is crucial for these mothers, their babies and clinicians to ensure a healthy life post-pandemic. Hence, we review the placental morphological changes due to COVID-19 to enhance the general understanding of how pregnant mothers, their placentas and unborn children may have been affected by this pandemic. Based on current literature, we deduced that COVID-19 pregnancies were oxygen deficient, which could further result in other pregnancy-related complications like preeclampsia and IUGR. Therefore, we present an up-to-date review of the COVID-19 pathophysiological implications on the placenta, covering the function of the placenta in COVID-19, the effects of this virus on the placenta, its functions and its link to other gestational complications. Furthermore, we highlight the possible effects of COVID-19 therapeutic interventions on pregnant mothers and their unborn children. Based on the literature, we strongly suggest that consistent surveillance for the mothers and infants from COVID-19 pregnancies be prioritised in the future. Though the pandemic is now in the past, its effects are long-term, necessitating the monitoring of clinical manifestations in the near future.
Topics: Female; Pregnancy; Humans; COVID-19; Placenta; SARS-CoV-2; Pregnancy Complications, Infectious; Infectious Disease Transmission, Vertical
PubMed: 37235921
DOI: 10.1016/j.placenta.2023.05.009 -
The Journal of Maternal-fetal &... Dec 2023N6-methyladenosine (m6A) is one of the predominant RNA epigenetic modifications that modify RNAs reversibly and dynamically by "writers" (methyltransferase), "erasers"... (Review)
Review
BACKGROUND
N6-methyladenosine (m6A) is one of the predominant RNA epigenetic modifications that modify RNAs reversibly and dynamically by "writers" (methyltransferase), "erasers" (demethylase), and "readers."
OBJECTIVE
This review aimed to provide a comprehensive understanding of the complexity of m6A regulation in the great obstetrical syndromes to understand its pathogenesis and potential therapeutic targets.
METHODS
The terms "placenta or trophoblast" and "m6A or N6-methyladenosine" were searched in PubMed databases (June 2023).
RESULTS
In this review, we discuss the regulatory role of m6A in the great obstetrical syndromes such as preeclampsia (PE), spontaneous abortion (SA), hyperglycemia in pregnancy (HIP) and fetal growth to emphasize the clinical relevance of m6A dysregulation in pregnancy. We also describe mechanisms that potentially involve the participation of m6A methylation, such as proliferation, invasion, migration, apoptosis, autophagy, endoplasmic reticulum stress, macrophage polarization, and inflammation.
CONCLUSION
We summarize the recent research progress on the role of m6A modification in the great obstetrical syndromes and placental function and provide a brief perspective on its prospective applications.
Topics: Pregnancy; Humans; Female; Placenta; Syndrome; Abortion, Spontaneous; Adenosine; Apoptosis
PubMed: 37474299
DOI: 10.1080/14767058.2023.2234541 -
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