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Reproduction (Cambridge, England) Jul 2020Appropriate human trophoblast lineage specification and differentiation is crucial for the establishment of normal placentation and maintenance of pregnancy. However,... (Review)
Review
Appropriate human trophoblast lineage specification and differentiation is crucial for the establishment of normal placentation and maintenance of pregnancy. However, due to the lack of proper modeling systems, the molecular mechanisms of these processes are still largely unknown. Much of the early studies in this area have been based on animal models and tumor-derived trophoblast cell lines, both of which are suboptimal for modeling this unique human organ. Recent advances in regenerative and stem cell biology methods have led to development of novel in vitro model systems for studying human trophoblast. These include derivation of human embryonic and induced pluripotent stem cells and establishment of methods for the differentiation of these cells into trophoblast, as well as the more recent derivation of human trophoblast stem cells. In addition, advances in culture conditions, from traditional two-dimensional monolayer culture to 3D culturing systems, have led to development of trophoblast organoid and placenta-on-a-chip model, enabling us to study human trophoblast function in context of more physiologically accurate environment. In this review, we will discuss these various model systems, with a focus on human trophoblast, and their ability to help elucidate the key mechanisms underlying placental development and function. This review focuses on model systems of human trophoblast differentiation, including advantages and limitations of stem cell-based culture, trophoblast organoid, and organ-on-a-chip methods and their applications in understanding placental development and disease.
Topics: Cell Differentiation; Epithelium; Female; Humans; Maternal-Fetal Exchange; Models, Biological; Placenta; Placentation; Pregnancy; Trophoblasts
PubMed: 32485667
DOI: 10.1530/REP-19-0428 -
Placenta Sep 2023To investigate the role of claudin-1 (CLDN1) in trophoblast invasion and endovascular trophoblast (enEVT) differentiation in early-onset preeclampsia (EOPE).
INTRODUCTION
To investigate the role of claudin-1 (CLDN1) in trophoblast invasion and endovascular trophoblast (enEVT) differentiation in early-onset preeclampsia (EOPE).
METHODS
The expression and localization of CLDN1 in normal (n = 18) and EOPE (n = 20) placental tissues were detected by immunohistochemical (IHC) staining, quantitative real-time polymerase chain reaction (qRT‒PCR) and Western blotting. Next, invasion, migration and tube formation assays were performed to explore the involvement of CLDN1 in trophoblast invasion and enEVT differentiation in trophoblast cell lines (HTR8/SVneo). Then, invasion and enEVT markers were analyzed via Western blotting and qRT‒PCR, respectively. Finally, we established an EOPE mouse model to detect the Cldn1 protein level.
RESULTS
CLDN1 expression was significantly decreased in EOPE placental tissues. Knockdown of CLDN1 suppressed HTR8/SVneo cell invasion, migration and the ability to penetrate the endothelial tube. Conversely, overexpression of CLDN1 promoted trophoblast invasion and the ability to invade the endothelial tube. Inhibition of CLDN1 decreased the protein expression of VIM and SNAIL along with downregulating IL1B and PECAM1 mRNA levels, while overexpression of CLDN1 gave the opposite results. In the EOPE mouse model, we found a decrease in Cldn1 expression in EOPE mouse placentas.
DISCUSSION
These results suggest that the downregulation of CLDN1 in trophoblast cells is involved in the pathogenesis of early-onset preeclampsia by affecting trophoblast invasion and enEVT differentiation.
Topics: Humans; Animals; Mice; Pregnancy; Female; Trophoblasts; Placenta; Claudin-1; Down-Regulation; Pre-Eclampsia; Cell Movement; Cell Differentiation
PubMed: 37523840
DOI: 10.1016/j.placenta.2023.07.010 -
Frontiers in Cellular and Infection... 2023is a ubiquitous apicomplexan parasite that can infect virtually any warm-blooded animal. Acquired infection during pregnancy and the placental breach, is at the core of... (Review)
Review
is a ubiquitous apicomplexan parasite that can infect virtually any warm-blooded animal. Acquired infection during pregnancy and the placental breach, is at the core of the most devastating consequences of toxoplasmosis. can severely impact the pregnancy's outcome causing miscarriages, stillbirths, premature births, babies with hydrocephalus, microcephaly or intellectual disability, and other later onset neurological, ophthalmological or auditory diseases. To tackle vertical transmission, it is important to understand the mechanisms underlying host-parasite interactions at the maternal-fetal interface. Nonetheless, the complexity of the human placenta and the ethical concerns associated with its study, have narrowed the modeling of parasite vertical transmission to animal models, encompassing several unavoidable experimental limitations. Some of these difficulties have been overcome by the development of different human cell lines and a variety of primary cultures obtained from human placentas. These cellular models, though extremely valuable, have limited ability to recreate what happens . During the last decades, the development of new biomaterials and the increase in stem cell knowledge have led to the generation of more physiologically relevant models. These cell cultures incorporate new dimensions and cellular diversity, emerging as promising tools for unraveling the poorly understood ´s infection mechanisms during pregnancy. Herein, we review the state of the art of 2D and 3D cultures to approach the biology of pertaining to vertical transmission, highlighting the challenges and experimental opportunities of these up-and-coming experimental platforms.
Topics: Animals; Humans; Pregnancy; Female; Placenta; Toxoplasma; Toxoplasmosis; Infectious Disease Transmission, Vertical; Models, Animal
PubMed: 36968102
DOI: 10.3389/fcimb.2023.1130901 -
Reproduction & Fertility Oct 2022The placenta plays an essential role at the beginning of life, nourishing and supporting the fetus, but its life span is limited. In late pregnancy, the placenta...
The placenta plays an essential role at the beginning of life, nourishing and supporting the fetus, but its life span is limited. In late pregnancy, the placenta develops signs of aging, including inflammation and impaired function, which may complicate pregnancy. Placentas also show another sign of aging - cells with extra or missing chromosomes. Chromosomally abnormal cells could gather in the placenta if they get stranded there and/or if the cells do not separate normally. Chromosome separation goes wrong in aging cells when the DNA sequences, which protect the ends of the chromosomes, erode. When chromosomes lose their protective caps, they fuse which leads to abnormal numbers of chromosomes. In this pilot study, for the first time, we found fusions between the caps in a human placenta when it reaches full term. More studies are needed to decide whether this has an influence on how the placenta works and outcomes of pregnancy.
Topics: Animals; Humans; Female; Pregnancy; Pilot Projects; Placenta
PubMed: 36374285
DOI: 10.1530/RAF-22-0065 -
Reproduction in Domestic Animals =... Sep 2021Retention of foetal membranes (RFM) is a major reproductive disorder in dairy cows. An appropriate immune response is important for a physiological expulsion of the...
Retention of foetal membranes (RFM) is a major reproductive disorder in dairy cows. An appropriate immune response is important for a physiological expulsion of the foetal membranes at parturition. Our study aims to provide a deeper insight into characteristics of foetal and maternal macrophages in bovine term placenta. We used transmission electron microscopy (TEM), immunohistochemistry and semi-quantitative RT-PCR to provide a deeper insight into characteristics of foetal and maternal macrophages in bovine term placenta. Semi-quantitative RT-PCR was used to define macrophage polarization in foetal and maternal compartments of normal term placenta. Gene expression of factors involved in M1 polarization [interferon regulatory factor-5 (IRF5), interleukin (IL)-12A, IL12B] and in M2 polarization (IL10) were studied. Ultrastructurally, foetal macrophages showed an irregular shape and large vacuoles, whereas the maternal macrophages were spindle shaped. By immunohistochemistry, macrophages were identified by a strong staining with the lysosomal marker Lysosome-associated membrane glycoprotein 1 (LAMP-1), while myofibroblast in the maternal stroma was positive for alpha-smooth muscle actin. We used the LAMP-1 marker to compare the density of foetal stromal macrophages in placentas of cows with RFM and in controls, but no statistically significant difference was observed. RT-PCR showed a higher expression of all studied genes in the maternal compartment of the placenta and generally a higher expression of M1-, compared to M2-associated genes. Our results indicated that at parturition placental macrophages predominantly show the pro-inflammatory M1 polarization. The higher expression of all the target genes in the maternal compartment may denote that maternal macrophages in bovine term placenta are more frequent than foetal macrophages.
Topics: Animals; Cattle; Female; Fetus; Macrophages; Parturition; Placenta; Pregnancy; Transcriptome
PubMed: 34174122
DOI: 10.1111/rda.13983 -
Journal of Pregnancy 2021Senescent cells have been demonstrated to release High Mobility Group Box 1 (HMGB1) which induces labor through an inflammatory pathway. This research is aimed at...
INTRODUCTION
Senescent cells have been demonstrated to release High Mobility Group Box 1 (HMGB1) which induces labor through an inflammatory pathway. This research is aimed at demonstrating whether telomere shortening, proinflammatory HMGB1, and oxidative damage marker 8-OHdG play a role in the placenta of preterm birth in comparison to term birth.
METHOD
A cross-sectional study on 67 full thickness of the placenta obtained from mothers with term and preterm birth. Mothers with clinical signs of infection (fever > 38°C, leukocytosis > 18000/L, or abnormal vaginal discharge) and other pregnancy complications were excluded. Real-time polymerase chain reaction was performed to measure T/S ratio and ELISA quantification to measure the amount of HMGB1 and 8-OHdG.
RESULT
A total of 34 placentas from preterm and 33 placentas from term birth were examined. Maternal characteristics were comparable between the two groups. There were no statistical difference of T/S ratio ( = 0.181), HMGB1 ( = 0.119), and 8-OHdG ( = 0.144) between the preterm and term groups. HMGB1 was moderately correlated with 8-OHdG ( = 0.314). Telomere T/S ratio of the placenta did not differ between preterm and term labor despite difference in gestational age, suggesting earlier shortening in the preterm group. It is possible that critical telomere length has been achieved in both term and preterm placenta that warrants labor through senescence process. The result of our study also showed that HMGB1 was not correlated to telomere length, due to the fact that HMGB1 is not upregulated until the critical length of telomere for senescence is exhibited.
CONCLUSION
Similar telomere length might be exhibited due to early telomere shortening in preterm birth that mimics the term placenta. The relationship between placental telomere shortening and HMGB1 release remains to be uncovered. Further research is needed to discover the factors leading to early telomere shortening in the placenta of preterm birth.
Topics: Cross-Sectional Studies; Female; Humans; Infant, Newborn; Oxidative Stress; Placenta; Pregnancy; Premature Birth; Telomere Shortening
PubMed: 34258068
DOI: 10.1155/2021/9923761 -
PloS One 2024The impact of COVID-19 on the placenta is poorly described, particularly among minority women.
INTRODUCTION
The impact of COVID-19 on the placenta is poorly described, particularly among minority women.
MATERIALS AND METHODS
This is a retrospective case-control study. Micro- and macroscopic placental pathologic findings were compared for 15 COVID-19 positive and 36 negative mothers. Cases and controls were frequency matched on gestational age, race, maternal comorbidities, and delivery type. Data from the electronic medical record were supplemented with independent review of microscopic slides.
RESULTS
Placentas from cases and controls were similar except the median distance from the site of the cord insertion to the nearest disk margin was statistically significantly shorter among placentas from COVID-19 positive cases (3.5 versus 6.0 cm, p = 0.006). Case status was not associated with an increased risk of placental pathologies.
CONCLUSION
There are few pathologic differences between placentas of COVID-19 positive and negative mothers. Additional studies are needed to investigate the role of timing of infection.
Topics: Humans; Female; COVID-19; Pregnancy; Placenta; Adult; Retrospective Studies; Case-Control Studies; Pregnancy Complications, Infectious; SARS-CoV-2
PubMed: 38781150
DOI: 10.1371/journal.pone.0302682 -
Placenta Jan 2021Women living with HIV experience more adverse birth outcomes; the mechanisms are not fully understood. We examined placenta morphology and associations with birth...
INTRODUCTION
Women living with HIV experience more adverse birth outcomes; the mechanisms are not fully understood. We examined placenta morphology and associations with birth outcomes in a Canadian cohort of women living with HIV (HIV) on antiretroviral therapy (ART) from conception and HIV-uninfected (HIV) women.
METHODS
Term placentas from 94 women (40 HIV, 54 HIV) were studied. Trimmed placenta weight was collected. Placenta digital photos were used to compute morphometric parameters. Regression models investigated associations between log-transformed placenta parameters and birth outcomes.
RESULTS
We observed a trend towards lower placenta weight and smaller placenta area in the HIV group, both of which were significantly associated with small for gestational age births. HIV serostatus was associated with 6-fold (95%CI 2-20) greater odds of having placenta area in the lowest quartile (<236 cm). Cord marginality (distance from the edge) was significantly lower in the HIV group (p = 0.004), with 35% of placenta having an abnormal (marginal or velamentous) cord insertion vs. 12.5% in the HIV group (p = 0.01). Velamentous cord insertion was seen in 13% of placentas in the HIV vs. 0% in HIV group (p = 0.02). A significant correlation between cord marginality and placenta thickness was observed in the HIV group, with a more marginal cord being associated with a thicker placenta. This correlation was not observed in the HIV group. HIV placentas exposed to protease inhibitors were significantly less circular compared to the HIV group (p = 0.03).
CONCLUSION
Our data suggest that HIV/ART exposure affects placenta morphology and is associated with higher rates of abnormal cord insertion.
Topics: Adult; Anti-Retroviral Agents; Female; HIV Infections; Humans; Infant, Newborn; Placenta; Pregnancy; Umbilical Cord
PubMed: 33310298
DOI: 10.1016/j.placenta.2020.12.004 -
Rapid Communications in Mass... Feb 2023We describe a label-free proteomics protocol for the interrogation of the placental proteome. Step-by-step directions, including tissue cleanup and preparation,...
We describe a label-free proteomics protocol for the interrogation of the placental proteome. Step-by-step directions, including tissue cleanup and preparation, proteolytic digestion, nanoLC-MS/MS data collection and data analysis, are provided. The workflow has been applied toward exploring differential protein expression patterns in placentas from women who have been exposed to drugs during pregnancy relative to those who have not. We collected 20 tissue specimens, each representing a combination of spatially diverse sections across the placenta. These specimens were analyzed in the work described here, to survey information across the entire organ. This protocol can be scaled up or down as needed.
Topics: Humans; Pregnancy; Female; Placenta; Tandem Mass Spectrometry; Proteomics; Proteolysis; Proteome
PubMed: 34486781
DOI: 10.1002/rcm.9189 -
Circulation Journal : Official Journal... Dec 2021Pregnant women with a Fontan circulation have a high risk of obstetric complications, such as preterm delivery and small for gestational age (SGA), which may be affected...
BACKGROUND
Pregnant women with a Fontan circulation have a high risk of obstetric complications, such as preterm delivery and small for gestational age (SGA), which may be affected by low blood flow to the placenta and hypoxia. This study investigated placental pathology in a Fontan circulation.Methods and Results:Eighteen pregnancies in 11 women with a Fontan circulation were reviewed. Pregnancy outcomes showed 9 miscarriages and 9 live births, with 4 preterm deliveries. Five neonates were SGA (<5th percentile). Eight placentas from live births in 7 women were available for the study. Five placentas had low weight placenta for gestational age, and 7 grossly showed a chronic subchorionic hematoma. Histological examination revealed all placentas had some form of histological hypoxic lesions: maternal vascular malperfusion in 7, fetal vascular malperfusion in 1, and other hypoxia-related lesions in 8. Quantitative analyses, including immunohistochemistry (CD31, CD68, and hypoxia inducible factor-1α antibodies) and Masson's trichrome staining, were also performed and compared with 5 control placentas. Capillary density and the area of fibrosis were significantly greater in placentas from women with a Fontan circulation than in control placentas.
CONCLUSIONS
Placentas in a Fontan circulation were characterized by a high frequency of low placental weight, chronic subchorionic hematoma, and constant histological hypoxic changes, which could reflect altered maternal cardiac conditions and lead to poor pregnancy outcomes.
Topics: Child; Female; Fetal Growth Retardation; Fontan Procedure; Hematoma; Humans; Hypoxia; Infant, Newborn; Infant, Small for Gestational Age; Placenta; Pregnancy
PubMed: 34497162
DOI: 10.1253/circj.CJ-21-0133