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Cellular and Molecular Life Sciences :... Jun 2022The use of in vitro tools to study trophoblast differentiation and function is essential to improve understanding of normal and abnormal placental development. The... (Review)
Review
The use of in vitro tools to study trophoblast differentiation and function is essential to improve understanding of normal and abnormal placental development. The relative accessibility of human placentae enables the use of primary trophoblasts and placental explants in a range of in vitro systems. Recent advances in stem cell models, three-dimensional organoid cultures, and organ-on-a-chip systems have further shed light on the complex microenvironment and cell-cell crosstalk involved in placental development. However, understanding each model's strengths and limitations, and which in vivo aspects of human placentation in vitro data acquired does, or does not, accurately reflect, is key to interpret findings appropriately. To help researchers use and design anatomically accurate culture models, this review both outlines our current understanding of placental development, and critically considers the range of established and emerging culture models used to study this, with a focus on those derived from primary tissue.
Topics: Cell Differentiation; Female; Humans; Placenta; Placentation; Pregnancy; Stem Cells; Trophoblasts
PubMed: 35753002
DOI: 10.1007/s00018-022-04407-x -
Human Reproduction Update Nov 2020The placenta is the active interface between mother and foetus, bearing the molecular marks of rapid development and exposures in utero. The placenta is routinely... (Meta-Analysis)
Meta-Analysis Review
BACKGROUND
The placenta is the active interface between mother and foetus, bearing the molecular marks of rapid development and exposures in utero. The placenta is routinely discarded at delivery, providing a valuable resource to explore maternal-offspring health and disease in pregnancy. Genome-wide profiling of the human placental transcriptome provides an unbiased approach to study normal maternal-placental-foetal physiology and pathologies.
OBJECTIVE AND RATIONALE
To date, many studies have examined the human placental transcriptome, but often within a narrow focus. This review aims to provide a comprehensive overview of human placental transcriptome studies, encompassing those from the cellular to tissue levels and contextualize current findings from a broader perspective. We have consolidated studies into overarching themes, summarized key research findings and addressed important considerations in study design, as a means to promote wider data sharing and support larger meta-analysis of already available data and greater collaboration between researchers in order to fully capitalize on the potential of transcript profiling in future studies.
SEARCH METHODS
The PubMed database, National Center for Biotechnology Information and European Bioinformatics Institute dataset repositories were searched, to identify all relevant human studies using 'placenta', 'decidua', 'trophoblast', 'transcriptome', 'microarray' and 'RNA sequencing' as search terms until May 2019. Additional studies were found from bibliographies of identified studies.
OUTCOMES
The 179 identified studies were classifiable into four broad themes: healthy placental development, pregnancy complications, exposures during pregnancy and in vitro placental cultures. The median sample size was 13 (interquartile range 8-29). Transcriptome studies prior to 2015 were predominantly performed using microarrays, while RNA sequencing became the preferred choice in more recent studies. Development of fluidics technology, combined with RNA sequencing, has enabled transcript profiles to be generated of single cells throughout pregnancy, in contrast to previous studies relying on isolated cells. There are several key study aspects, such as sample selection criteria, sample processing and data analysis methods that may represent pitfalls and limitations, which need to be carefully considered as they influence interpretation of findings and conclusions. Furthermore, several areas of growing importance, such as maternal mental health and maternal obesity are understudied and the profiling of placentas from these conditions should be prioritized.
WIDER IMPLICATIONS
Integrative analysis of placental transcriptomics with other 'omics' (methylome, proteome and metabolome) and linkage with future outcomes from longitudinal studies is crucial in enhancing knowledge of healthy placental development and function, and in enabling the underlying causal mechanisms of pregnancy complications to be identified. Such understanding could help in predicting risk of future adversity and in designing interventions that can improve the health outcomes of both mothers and their offspring. Wider collaboration and sharing of placental transcriptome data, overcoming the challenges in obtaining sufficient numbers of quality samples with well-defined clinical characteristics, and dedication of resources to understudied areas of pregnancy will undoubtedly help drive the field forward.
Topics: Female; Gene Expression Profiling; Humans; Microarray Analysis; Placenta; Placentation; Pregnancy; Pregnancy Complications; Pregnancy Trimester, First; Trophoblasts
PubMed: 33043357
DOI: 10.1093/humupd/dmaa028 -
Pflugers Archiv : European Journal of... Jul 2023Hypertensive disorders of pregnancy are complications that can lead to maternal and infant mortality and morbidity. Hypertensive disorders of pregnancy are generally... (Review)
Review
Hypertensive disorders of pregnancy are complications that can lead to maternal and infant mortality and morbidity. Hypertensive disorders of pregnancy are generally defined as hypertension and may be accompanied by other end organ damages including proteinuria, maternal organ disturbances including renal insufficiency, neurological complications, thrombocytopenia, impaired liver function, or uteroplacental dysfunction such as fetal growth restriction and stillbirth. Although the causes of these hypertensive disorders of pregnancy are multifactorial and elusive, they seem to share some common vascular-related mechanisms, including diseased spiral arteries, placental ischemia, and endothelial dysfunction. Recently, preeclampsia is being considered as a vascular disorder. Unfortunately, due to the complex etiology of preeclampsia and safety concerns on drug usage during pregnancy, there is still no effective pharmacological treatments available for preeclampsia yet. An emerging area of interest in this research field is the potential beneficial effects of dietary intervention on reducing the risk of preeclampsia. Recent studies have been focused on the association between deficiencies or excesses of some nutrients and complications during pregnancy, fetal growth and development, and later risk of cardiovascular and metabolic diseases in the offspring. In this review, we discuss the involvement of placental vascular dysfunction in preeclampsia. We summarize the current understanding of the association between abnormal placentation and preeclampsia in a vascular perspective. Finally, we evaluate several studied dietary supplementations to prevent and reduce the risk of preeclampsia, targeting placental vascular development and function, leading to improved pregnancy and postnatal outcomes.
Topics: Pregnancy; Female; Humans; Pre-Eclampsia; Placenta; Hypertension, Pregnancy-Induced; Placentation; Dietary Supplements
PubMed: 37043045
DOI: 10.1007/s00424-023-02810-2 -
EBioMedicine Sep 2023Dengue virus (DENV) infection during pregnancy increases the risk of adverse fetal outcomes, which has become a new clinical challenge. However, the underlying mechanism...
BACKGROUND
Dengue virus (DENV) infection during pregnancy increases the risk of adverse fetal outcomes, which has become a new clinical challenge. However, the underlying mechanism remains unknown.
METHODS
The effect of DENV-2 infection on fetuses was investigated using pregnant interferon α/β receptor-deficient (Ifnar1) mice. The histopathological changes in the placentas were analyzed by morphological techniques. A mouse inflammation array was used to detect the cytokine and chemokine profiles in the serum and placenta. The infiltration characteristics of inflammatory cells in the placentas were evaluated by single-cell RNA sequencing.
FINDINGS
Fetal growth restriction observed in DENV-2 infection was mainly caused by the destruction of the placental vasculature rather than direct damage from the virus in our mouse model. After infection, neutrophil infiltration into the placenta disrupts the expression profile of matrix metalloproteinases, which leads to placental dysvascularization and insufficiency. Notably, similar histopathological changes were observed in the placentas from DENV-infected puerperae.
INTERPRETATION
Neutrophils play key roles in placental histopathological damage during DENV infection, which indicates that interfering with aberrant neutrophil infiltration into the placenta may be an important therapeutic target for adverse pregnancy outcomes in DENV infection.
FUNDING
The National Key Research and Development Plans of China (2021YFC2300200-02 to J.A., 2019YFC0121905 to Q.Z.C.), the National Natural Science Foundation of China (NSFC) (U1902210 and 81972979 to J. A., 81902048 to Z. Y. S., and 82172266 to P.G.W.), and the Support Project of High-level Teachers in Beijing Municipal Universities in the Period of 13th Five-year Plan, China (IDHT20190510 to J. A.).
Topics: Humans; Mice; Pregnancy; Female; Animals; Placenta; Dengue Virus; Fetal Growth Retardation; Neutrophil Infiltration; Cytokines
PubMed: 37544202
DOI: 10.1016/j.ebiom.2023.104739 -
Hypertension (Dallas, Tex. : 1979) Nov 2023Preeclampsia is a hypertensive disorder of pregnancy characterized by chronic placental ischemia and suppression of proangiogenic proteins, causing oxidative stress,...
BACKGROUND
Preeclampsia is a hypertensive disorder of pregnancy characterized by chronic placental ischemia and suppression of proangiogenic proteins, causing oxidative stress, hypertension, and maternal systemic organ damage. The transcription factor, PPARγ (peroxisome proliferator-activated receptor-γ) promotes healthy trophoblast differentiation but is dysregulated in the preeclampsia placenta. Our study identifies the beneficial impact of Rosiglitazone-mediated PPARγ-activation in the stressed preeclampsia placenta.
METHODS
We used first trimester placentas, preeclamptic and preterm control placentas, and human trophoblast cell lines to study PPARγ activation.
RESULTS
Induction of PPARγ activates cell growth and antioxidative stress pathways, including the gene, heme oxygenase 1 (). Protein expression of both PPARγ and HO1 (heme oxygenase 1) are reduced in preeclamptic placentas, but Rosiglitazone restores HO1 signaling in a PPARγ-dependent manner.
CONCLUSIONS
Restoring disrupted pathways by PPARγ in preeclampsia offers a potential therapeutic pathway to reverse placental damage, extending pregnancy duration, and reduce maternal sequelae. Future research should aim to understand the full scope of impaired PPARγ signaling in the human placenta and focus on compounds for safe use during pregnancy to prevent severe perinatal morbidity and mortality.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Heme Oxygenase-1; Placenta; PPAR gamma; Pre-Eclampsia; Rosiglitazone; Trophoblasts
PubMed: 37702083
DOI: 10.1161/HYPERTENSIONAHA.123.21645 -
Viruses Dec 2019The placenta is a unique mixed organ, composed of both maternal and fetal tissues, that is formed only during pregnancy and serves as the key physiological and... (Review)
Review
The placenta is a unique mixed organ, composed of both maternal and fetal tissues, that is formed only during pregnancy and serves as the key physiological and immunological barrier preventing maternal-fetal transmission of pathogens. Several viruses can circumvent this physical barrier and enter the fetal compartment, resulting in miscarriage, preterm birth, and birth defects, including microcephaly. The mechanisms underlying viral strategies to evade the protective role of placenta are poorly understood. Here, we reviewed the role of trophoblasts and Hofbauer cells in the placenta and have highlighted characteristics of vertical and perinatal infections caused by a wide range of viruses. Moreover, we explored current progress and future opportunities in cellular targets, pathogenesis, and underlying biological mechanisms of congenital viral infections, as well as novel research models and tools to study the placenta.
Topics: Animals; Biomarkers; Disease Models, Animal; Disease Susceptibility; Female; Host-Pathogen Interactions; Humans; Infectious Disease Transmission, Vertical; Placenta; Pregnancy; Pregnancy Complications, Infectious; Research; Virus Diseases
PubMed: 31861492
DOI: 10.3390/v12010005 -
Human Pathology Jul 2022Placental pathology can identify characteristic features of specific infectious pathogens. The histopathology of acute SARS-CoV-2 placental infection and exposure...
Placental pathology can identify characteristic features of specific infectious pathogens. The histopathology of acute SARS-CoV-2 placental infection and exposure without infection has been well described. However, whether the characteristic placental pathology persists after the acute phase of the infection is less clear. We retrospectively identified 67 COVID-19-recovered pregnant patients who had placental pathology available. After reviewing the gross and histopathology, we categorized the findings and studied the placentas for evidence of chronic infection by immunohistochemistry for the spike protein of the virus. We found these placentas showed significantly increased prevalence of maternal and a trend towards significance of fetal vascular malperfusion when compared to a control group of placentas examined for the sole indication of maternal group B streptococcal colonization. None of the COVID-19-recovered placentas showed expression of the viral spike protein; therefore, we found no evidence of persistent infection of the placenta in women with a history of COVID-19 during their pregnancy. We conclude that recovery from a SARS-CoV-2 infection during pregnancy puts the pregnancy at risk for specific pathology.
Topics: COVID-19; Female; Humans; Placenta; Pregnancy; Pregnancy Complications, Infectious; Retrospective Studies; SARS-CoV-2; Spike Glycoprotein, Coronavirus
PubMed: 35405186
DOI: 10.1016/j.humpath.2022.04.005 -
Biology of Sex Differences Dec 2022Pregnancy complications vary based on the fetus's genetic sex, which may, in part, be modulated by the placenta. Furthermore, developmental differences early in life can...
BACKGROUND
Pregnancy complications vary based on the fetus's genetic sex, which may, in part, be modulated by the placenta. Furthermore, developmental differences early in life can have lifelong health outcomes. Yet, sex differences in gene expression within the placenta at different timepoints throughout pregnancy and comparisons to adult tissues remains poorly characterized.
METHODS
Here, we collect and characterize sex differences in gene expression in term placentas (≥ 36.6 weeks; 23 male XY and 27 female XX). These are compared with sex differences in previously collected first trimester placenta samples and 42 non-reproductive adult tissues from GTEx.
RESULTS
We identify 268 and 53 sex-differentially expressed genes in the uncomplicated late first trimester and term placentas, respectively. Of the 53 sex-differentially expressed genes observed in the term placentas, 31 are also sex-differentially expressed genes in the late first trimester placentas. Furthermore, sex differences in gene expression in term placentas are highly correlated with sex differences in the late first trimester placentas. We found that sex-differential gene expression in the term placenta is significantly correlated with sex differences in gene expression in 42 non-reproductive adult tissues (correlation coefficient ranged from 0.892 to 0.957), with the highest correlation in brain tissues. Sex differences in gene expression were largely driven by gene expression on the sex chromosomes. We further show that some gametologous genes (genes with functional copies on X and Y) will have different inferred sex differences if the X-linked gene expression in females is compared to the sum of the X-linked and Y-linked gene expression in males.
CONCLUSIONS
We find that sex differences in gene expression are conserved in late first trimester and term placentas and that these sex differences are conserved in adult tissues. We demonstrate that there are sex differences associated with innate immune response in late first trimester placentas but there is no significant difference in gene expression of innate immune genes between sexes in healthy full-term placentas. Finally, sex differences are predominantly driven by expression from sex-linked genes.
Topics: Pregnancy; Female; Male; Adult; Humans; Sex Characteristics; Placenta; Pregnancy Trimester, First
PubMed: 36550527
DOI: 10.1186/s13293-022-00470-y -
International Journal of Molecular... Feb 2021Aggrephagy is defined as the selective degradation of aggregated proteins by autophagosomes. Protein aggregation in organs and cells has been highlighted as a cause of... (Review)
Review
Aggrephagy is defined as the selective degradation of aggregated proteins by autophagosomes. Protein aggregation in organs and cells has been highlighted as a cause of multiple diseases, including neurodegenerative diseases, cardiac failure, and renal failure. Aggregates could pose a hazard for cell survival. Cells exhibit three main mechanisms against the accumulation of aggregates: protein refolding by upregulation of chaperones, reduction of protein overload by translational inhibition, and protein degradation by the ubiquitin-proteasome and autophagy-lysosome systems. Deletion of autophagy-related genes reportedly contributes to intracellular protein aggregation in vivo. Some proteins recognized in aggregates in preeclamptic placentas include those involved in neurodegenerative diseases. As aggregates are derived both intracellularly and extracellularly, special endocytosis for extracellular aggregates also employs the autophagy machinery. In this review, we discuss how the deficiency of aggrephagy and/or macroautophagy leads to poor placentation, resulting in preeclampsia or fetal growth restriction.
Topics: Animals; Female; Humans; Lysosomes; Macroautophagy; Placenta; Pre-Eclampsia; Pregnancy; Protein Aggregation, Pathological
PubMed: 33670947
DOI: 10.3390/ijms22052432 -
American Journal of Obstetrics and... May 2023Pathologic examination of the placenta can provide insight into likely (and unlikely) causes of antepartum and intrapartum events, diagnoses with urgent clinical...
Pathologic examination of the placenta can provide insight into likely (and unlikely) causes of antepartum and intrapartum events, diagnoses with urgent clinical relevance, prognostic information for mother and infant, support for practice evaluation and improvement, and insight into advancing the sciences of obstetrics and neonatology. Although it is true that not all placentas require pathologic examination (although alternative opinions have been expressed), prioritization of placentas for pathologic examination should be based on vetted indications such as maternal comorbidities or pregnancy complications in which placental pathology is thought to be useful for maternal or infant care, understanding pathophysiology, or practice modifications. Herein we provide placental triage criteria for the obstetrical and neonatal provider based on publications and expert opinion of 16 placental pathologists and a pathologists' assistant, formulated using a modified Delphi approach. These criteria include indications in which placental pathology has clinical relevance, such as pregnancy loss, maternal infection, suspected abruption, fetal growth restriction, preterm birth, nonreassuring fetal heart testing requiring urgent delivery, preeclampsia with severe features, or neonates with early evidence of multiorgan system failure including neurologic compromise. We encourage a focused gross examination by the provider or an attendant at delivery for all placentas and provide guidance for this examination. We recommend that any placenta that is abnormal on gross examination undergo a complete pathology examination. In addition, we suggest practice criteria for placental pathology services, including a list of critical values to be used by the relevant provider. We hope that these sets of triage indications, criteria, and practice suggestions will facilitate appropriate submission of placentas for pathologic examination and improve its relevance to clinical care.
Topics: Pregnancy; Infant, Newborn; Female; Humans; Placenta; Premature Birth; Pregnancy Complications; Obstetrics; Fetal Growth Retardation
PubMed: 36549567
DOI: 10.1016/j.ajog.2022.12.017