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Scientific Reports Mar 2022Placental function requires organized growth, transmission of nutrients, and an anti-inflammatory milieu between the maternal and fetal interface, but placental factors...
Placental function requires organized growth, transmission of nutrients, and an anti-inflammatory milieu between the maternal and fetal interface, but placental factors important for its function remain unclear. Renalase is a pro-survival, anti-inflammatory flavoprotein found to be critical in other tissues. We examined the potential role of renalase in placental development. PCR, bulk RNA sequencing, immunohistochemistry, and immunofluorescence for renalase and its binding partners, PMCA4b and PZP, were performed on human placental tissue from second-trimester and full-term placentas separated into decidua, placental villi and chorionic plates. Quantification of immunohistochemistry was used to localize renalase across time course from 17 weeks to term. Endogenous production of renalase was examined in placental tissue and organoids. Renalase and its receptor PMCA4b transcripts and proteins were present in all layers of the placenta. Estimated RNLS protein levels did not change with gestation in the decidual samples. However, placental villi contained more renalase immunoreactive cells in fetal than full-term placental samples. RNLS co-labeled with markers for Hofbauer cells and trophoblasts within the placental villi. Endogenous production of RNLS, PMCA4b, and PZP by trophoblasts was validated in placental organoids. Renalase is endogenously expressed throughout placental tissue and specifically within Hofbauer cells and trophoblasts, suggesting a potential role for renalase in placental development and function. Future studies should assess renalase's role in normal and diseased human placenta.
Topics: Chorionic Villi; Decidua; Female; Humans; Monoamine Oxidase; Placenta; Placentation; Plasma Membrane Calcium-Transporting ATPases; Pregnancy; Trophoblasts
PubMed: 35322081
DOI: 10.1038/s41598-022-08817-6 -
Journal of Visualized Experiments : JoVE Apr 2023The placenta is an essential organ that regulates and maintains mammalian development in utero. The placenta is responsible for the transfer of nutrients and waste...
The placenta is an essential organ that regulates and maintains mammalian development in utero. The placenta is responsible for the transfer of nutrients and waste between the mother and fetus and the production and delivery of growth factors and hormones. Placental genetic manipulations in mice are critical for understanding the placenta's specific role in prenatal development. Placental-specific Cre-expressing transgenic mice have varying effectiveness, and other methods for placental gene manipulation can be useful alternatives. This paper describes a technique to directly alter placental gene expression using CRISPR gene manipulation, which can be used to modify the expression of targeted genes. Using a relatively advanced surgical approach, pregnant dams undergo a laparotomy on embryonic day 12.5 (E12.5), and a CRISPR plasmid is delivered by a glass micropipette into the individual placentas. The plasmid is immediately electroporated after each injection. After dam recovery, the placentas and embryos can continue development until assessment at a later time point. The evaluation of the placenta and offspring after the use of this technique can determine the role of time-specific placental function in development. This type of manipulation will allow for a better understanding of how placental genetics and function impact fetal growth and development in multiple disease contexts.
Topics: Pregnancy; Female; Mice; Animals; Placenta; Clustered Regularly Interspaced Short Palindromic Repeats; Fetal Development; Fetus; Mammals
PubMed: 37125793
DOI: 10.3791/64760 -
Reproductive Sciences (Thousand Oaks,... Aug 2021Preeclampsia complicates 5-8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress and mitochondrial abnormalities...
Preeclampsia complicates 5-8% of all pregnancies worldwide, and although its pathophysiology remains obscure, placental oxidative stress and mitochondrial abnormalities are considered to play a key role. Mitochondrial abnormalities in preeclamptic placentae have been described, but the extent to which mitochondrial content and the molecular pathways controlling this (mitochondrial biogenesis and mitophagy) are affected in preeclamptic placentae is unknown. Therefore, in preeclamptic (n = 12) and control (n = 11) placentae, we comprehensively assessed multiple indices of placental antioxidant status, mitochondrial content, mitochondrial biogenesis, mitophagy, and mitochondrial fusion and fission. In addition, we also explored gene expression profiles related to inflammation and apoptosis. Preeclamptic placentae were characterized by higher levels of oxidized glutathione, a higher total antioxidant capacity, and higher mRNA levels of the mitochondrial-located antioxidant enzyme manganese-dependent superoxide dismutase 2 compared to controls. Furthermore, mitochondrial content was significantly lower in preeclamptic placentae, which was accompanied by an increased abundance of key constituents of glycolysis. Moreover, mRNA and protein levels of key molecules involved in the regulation of mitochondrial biogenesis were lower in preeclamptic placentae, while the abundance of constituents of the mitophagy, autophagy, and mitochondrial fission machinery was higher compared to controls. In addition, we found evidence for activation of apoptosis and inflammation in preeclamptic placentae. This study is the first to comprehensively demonstrate abnormalities at the level of the mitochondrion and the molecular pathways controlling mitochondrial content/function in preeclamptic placentae. These aberrations may well contribute to the pathophysiology of preeclampsia by upregulating placental inflammation, oxidative stress, and apoptosis. Graphical Abstract.
Topics: Adult; Antioxidants; Apoptosis; Female; Humans; Inflammation; Mitochondria; Oxidative Stress; Placenta; Pre-Eclampsia; Pregnancy; Superoxide Dismutase; Trophoblasts
PubMed: 33523425
DOI: 10.1007/s43032-021-00464-y -
Biology of Reproduction Jun 2021Since the beginning of the current coronavirus outbreak (COVID-19), there has been great concern over a disease that has spread rapidly in several countries worldwide,... (Review)
Review
Since the beginning of the current coronavirus outbreak (COVID-19), there has been great concern over a disease that has spread rapidly in several countries worldwide, with the result of several deaths, including deaths of pregnant women. Therefore, the aim of this study was to conduct a literature review on placental changes in infected pregnant women and/or asymptomatic carriers of COVID-19 during pregnancy, aiming at the possible vertical transmission. A systematic collection was carried out on the effects of that COVID-19 can cause directly and/or indirectly to pregnancy and the placenta in the following databases: Pubmed, Science Direct, Scielo, Lilacs, and Web of Science. For search, the following descriptors were used: placenta, pregnant woman, COVID-19, maternal-fetal. The results indicate transplacental transmission in some cases reviewed in many reports from this study. The presence of the virus was seen in the amniotic fluid, umbilical cord, and peripheral blood. Finally, pathological studies suggest that there are morphological changes related to infection in the placentas. We can conclude that, based on the researched material, there is little evidence of transplacental vertical viral transmission and its respective morphological changes related to viral infection in the placenta.
Topics: COVID-19; Female; Humans; Infectious Disease Transmission, Vertical; Placenta; Pregnancy; Pregnancy Complications, Infectious; SARS-CoV-2
PubMed: 33677519
DOI: 10.1093/biolre/ioab037 -
American Journal of Clinical Pathology Jun 2020To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy.
OBJECTIVES
To describe histopathologic findings in the placentas of women with coronavirus disease 2019 (COVID-19) during pregnancy.
METHODS
Pregnant women with COVID-19 delivering between March 18, 2020, and May 5, 2020, were identified. Placentas were examined and compared to historical controls and women with placental evaluation for a history of melanoma.
RESULTS
Sixteen placentas from patients with severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) were examined (15 with live birth in the third trimester, 1 delivered in the second trimester after intrauterine fetal demise). Compared to controls, third trimester placentas were significantly more likely to show at least one feature of maternal vascular malperfusion (MVM), particularly abnormal or injured maternal vessels, and intervillous thrombi. Rates of acute and chronic inflammation were not increased.The placenta from the patient with intrauterine fetal demise showed villous edema and a retroplacental hematoma.
CONCLUSIONS
Relative to controls, COVID-19 placentas show increased prevalence of decidual arteriopathy and other features of MVM, a pattern of placental injury reflecting abnormalities in oxygenation within the intervillous space associated with adverse perinatal outcomes. Only 1 COVID-19 patient was hypertensive despite the association of MVM with hypertensive disorders and preeclampsia. These changes may reflect a systemic inflammatory or hypercoagulable state influencing placental physiology.
Topics: Adult; Betacoronavirus; COVID-19; Case-Control Studies; Coronavirus Infections; Female; Humans; Pandemics; Placenta; Pneumonia, Viral; Pregnancy; Pregnancy Complications, Infectious; Pregnancy Trimester, Third; SARS-CoV-2
PubMed: 32441303
DOI: 10.1093/ajcp/aqaa089 -
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 -
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 -
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