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Placenta Sep 2017Abnormal placental function in maternal diabetes affects fetal health and can predispose offspring to metabolic diseases in later life. There are fetal sex-specific...
Abnormal placental function in maternal diabetes affects fetal health and can predispose offspring to metabolic diseases in later life. There are fetal sex-specific differences in placenta structure and gene expression, which may affect placental responses to maternal diabetes. The present study examined the effects of maternal diabetes on indices of mitochondrial biogenesis in placentae from male and female offspring. Mitochondrial DNA (mtDNA) copy number and expression of key regulators of mitochondrial biogenesis were assessed in placentae from 19 diabetic and 23 non-diabetic women. The abundance of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α) and mitochondria transcription factor A (TFAM) were lower in female placentae compared to males, but not mtDNA content. In male offspring, maternal diabetes was associated with decreased placental PGC-1α and TFAM, and mitochondrial DNA (mtDNA) content. Male placental TFAM levels were highly correlated with PGC-1α and mtDNA content. However, despite decreased PGC-1α, concomitant changes in TFAM and mtDNA content by diabetes were not observed in females. In addition, TFAM abundance in female placentae was not correlated with PGC-1α or mtDNA content. In summary, placental PGC-1α/TFAM/mitochondrial biogenesis pathway is affected by maternal diabetes and offspring sex. Decreased PGC-1α in response to maternal diabetes plausibly contributes to impaired mitochondrial biogenesis in placentae of male offspring, which may affect long-term health and explain some of enhanced risk of future metabolic diseases in males.
Topics: Adult; Blood Glucose; DNA, Mitochondrial; DNA-Binding Proteins; Diabetes, Gestational; Female; Humans; Longitudinal Studies; Male; Mitochondrial Proteins; Organelle Biogenesis; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Placenta; Pregnancy; Sex Factors; Transcription Factors; Young Adult
PubMed: 28864016
DOI: 10.1016/j.placenta.2017.06.001 -
Placenta Apr 2011Preeclamptic women have increased plasma levels of free fetal hemoglobin (HbF), increased gene expression of placental HbF and accumulation of free HbF in the placental...
BACKGROUND
Preeclamptic women have increased plasma levels of free fetal hemoglobin (HbF), increased gene expression of placental HbF and accumulation of free HbF in the placental vascular lumen. Free hemoglobin (Hb) is pro-inflammatory, and causes oxidative stress and tissue damage.
METHODOLOGY
To show the impact of free Hb in PE, we used the dual ex vivo placental perfusion model. Placentas were perfused with Hb and investigated for physical parameters, Hb leakage, gene expression and morphology. The protective effects of α(1)-microglobulin (A1M), a heme- and radical-scavenger and antioxidant, was investigated.
RESULTS
Hb-addition into the fetal circulation led to a significant increase of the perfusion pressure and the feto-maternal leakage of free Hb. Morphological damages similar to the PE placentas were observed. Gene array showed up-regulation of genes related to immune response, apoptosis, and oxidative stress. Simultaneous addition of A1M to the maternal circulation inhibited the Hb leakage, morphological damage and gene up-regulation. Furthermore, perfusion with Hb and A1M induced a significant up-regulation of extracellular matrix genes.
SIGNIFICANCE
The ex vivo Hb-perfusion of human placenta resulted in physiological and morphological changes and a gene expression profile similar to what is observed in PE placentas. These results underline the potentially important role of free Hb in PE etiology. The damaging effects were counteracted by A1M, suggesting a role of this protein as a new potential PE therapeutic agent.
Topics: Alpha-Globulins; Female; Fetal Hemoglobin; Gene Expression Profiling; Hemoglobins; Humans; In Vitro Techniques; Oxidative Stress; Perfusion; Placenta; Pre-Eclampsia; Pregnancy; Up-Regulation
PubMed: 21356557
DOI: 10.1016/j.placenta.2011.01.017 -
Indian Journal of Pathology &... 2023Coronavirus 2019 infection (COVID 19) is an ongoing pandemic caused by pathogenic RNA viruses called severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). It has... (Observational Study)
Observational Study
BACKGROUND
Coronavirus 2019 infection (COVID 19) is an ongoing pandemic caused by pathogenic RNA viruses called severe acute respiratory syndrome coronavirus-2 (SARS-COV-2). It has affected people of all ages, with high morbidity and mortality among the elderly and immunocompromised population. Limited information is available on the effects of COVID-19 infection on pregnancy.
AIM
To describe the histopathological changes in the placental tissue of SARS-CoV-2 infected term mothers with no comorbidities and to correlate with neonatal outcome.
MATERIALS AND METHODS
This observational study was conducted in the Department of Pathology, KMCH institute of health sciences and research, Coimbatore from May 1, 2020 to November 30, 2020 for 6 months. Placental tissues of all COVID-19-positive term mothers with no comorbidities were included in this study. Histopathological examination of placentae was carried out and clinical data of mothers and newborn babies were obtained from medical records.
RESULTS
Histopathological examination of 64 placental tissue of COVID-19 mothers showed predominantly the features of fetal vascular malperfusion like stem villi vasculature thrombus, villous congestion, and avascular villi. No significant correlation was obtained in comparison with parity and symptomatic status of the mothers. However, histopathological changes were more prominent among symptomatic patients. The newborn babies born to these mothers showed no adverse outcome.
CONCLUSION
This study concluded that though COVID-19 infection in normal term pregnant women was associated with increased prevalence of features of fetal vascular malperfusion, there was no significant morbidity in the health status of both COVID-19 mothers and their neonates.
Topics: Placenta; COVID-19; Humans; Female; Pregnancy; Adult; Chorionic Villi; Infant, Newborn; Thrombosis; Pregnancy Complications, Infectious
PubMed: 37077072
DOI: 10.4103/ijpm.ijpm_237_21 -
Journal of Medicine and Life 2015Preeclampsia is a unique pregnancy-related disease that affects 5-7% pregnancies worldwide. Placental architecture is modified in PE and eclampsia. Placental morphology...
Preeclampsia is a unique pregnancy-related disease that affects 5-7% pregnancies worldwide. Placental architecture is modified in PE and eclampsia. Placental morphology and cellular arrangement are important for oxygen delivery from the mother to the fetus. Fetal growth and well-being after 20 weeks of gestation are dependent upon successful placental development. This, in turn, is achieved by an enhanced maternal blood supply to the placenta (normal uterine artery Doppler) and growth/ differentiation of the gas-exchanging placental villi. Conversely, pregnancy with severe placental insufficiency exhibits abnormalities both in uterine artery and in umbilical artery Doppler, and results in adverse perinatal outcome. The evaluation of placental functioning is possible nowadays through ultrasound examinations. Sonographic images associated with placental lesions include cystic areas, heterogeneous appearance of the placental mass, and thick or thin placentas. Sonographic evidence of destructive placental lesions is defined as the evolution of irregular cystic spaces with echogenic borders - the echogenic cystic lesions. Histological examinations of placenta may confirm these antepartum observations. Decidual vasculopathy and accelerated villous maturity are considered indicative of uteroplacental vascular insufficiency. Perivillous fibrin deposition and intervillous fibrin are considered indicative of intervillous coagulation. Detailed sonographic evaluation of the placenta and histopathological confirmation after birth are used to identify lesions associated with preeclampsia, intrauterine growth restriction and adverse short and long-term perinatal outcome, but the presence of cystic images in the placenta is not uniformly associated with adverse perinatal outcome. Combining Doppler studies with placental texture studies may lead to satisfactory results.
Topics: Female; Humans; Placenta; Pre-Eclampsia; Pregnancy; Ultrasonography
PubMed: 26366223
DOI: No ID Found -
Romanian Journal of Morphology and... 2022Maternal obesity is associated with increased maternal and fetal morbidity and mortality, with an increased risk of gestational diabetes mellitus (GDM) and preeclampsia...
Maternal obesity is associated with increased maternal and fetal morbidity and mortality, with an increased risk of gestational diabetes mellitus (GDM) and preeclampsia (PE). This prospective study histopathologically analyzes the placentas obtained from 34 pregnant obese women studied between October 2016 and May 2020. The 10 cases of term placentas from obese pregnancies with GDM and the 12 cases with PE were examined by the Hematoxylin-Eosin (HE), Masson's trichrome (MT) and Periodic Acid-Schiff-Hematoxylin (PAS-H) classical stainings, and by the immunohistochemical evaluation and compared to placentae from uncomplicated term obese pregnancies (12 cases). We did not meet placental histopathological (HP) abnormalities that we could classify as characteristic only for the state of obese pregnancy, but we did find placental changes associated with PE and GDM, in the context of obese pregnancy. In the case of association with PE, there were common lesions, manifested by intra- and perivillous fibrinoid deposition, calcification, and placental infarction area, to which were added numerous syncytial knots. In the case of obese pregnancy associated with GDM, we found, in addition to common placental lesions of obesity, intravillositary vascular edema and in the terminal villi appearing chorangiosis. This study revealed a number of HP changes that occur in maternal obesity, even in uncomplicated obese pregnancies. A characteristic of obese pregnancies associated with PE was the presence of numerous syncytial knots, and in obese pregnancies associated with GDM, the most common HP lesion was placental chorangiosis. Certainly, we cannot conclude that these HP lesions are specific to a particular pathology, but they belong primarily to the status of maternal obesity.
Topics: Diabetes, Gestational; Female; Hematoxylin; Humans; Obesity; Obesity, Maternal; Placenta; Pre-Eclampsia; Pregnancy; Pregnancy Outcome; Prospective Studies
PubMed: 36074672
DOI: 10.47162/RJME.63.1.09 -
Placenta Apr 2021Chronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of third trimester placenta, which contributes to major adverse obstetric outcomes. However,...
INTRODUCTION
Chronic villitis of unknown etiology (VUE) is a chronic inflammatory lesion of third trimester placenta, which contributes to major adverse obstetric outcomes. However, the inciting factors and mechanisms by which VUE contributes to adverse outcomes are poorly understood. This limits our ability to develop preventions or interventions. Our goals were to determine whether viruses can be detected in placental tissues with VUE and to determine whether gene expression profiles support an antiviral response.
METHODS
We extracted RNA and DNA from 20 placentas with high-grade chronic villitis and 20 control placentas without inflammation. Viruses were assessed using ViroCap viral nucleic acid enrichment coupled with metagenomic sequencing. RNA sequencing was used to evaluate the inflammatory gene expression profiles in each placenta.
RESULTS
We detected at least 1 virus in 50% of the samples tested. We found that herpesviruses, were found more frequently in cases compared with controls (P = 0.01). Antiviral pathways, including defense response to virus, interferon gamma response, and IFN alpha/beta response, were upregulated in cases. We observed two clusters of gene expression profiles in the VUE cases, suggesting multiple inflammatory profiles are associated with VUE.
DISCUSSION
These data support a viral etiology for some cases of VUE. Furthermore, gene expression profiles suggest the possibility of more than one cause or manifestation of VUE. Viral mechanisms should be explored as potential targets for prevention or intervention in VUE.
Topics: Adult; Case-Control Studies; Chorionic Villi; Female; Humans; Inflammation; Placenta; Placenta Diseases; Pregnancy; Retrospective Studies; Young Adult
PubMed: 33730616
DOI: 10.1016/j.placenta.2021.02.020 -
Placenta Mar 20233-dimensional trophoblast organoids (TB-ORG) represent a reliable model for studying extravillous trophoblast (EVT) lineage formation and differentiation. However,...
3-dimensional trophoblast organoids (TB-ORG) represent a reliable model for studying extravillous trophoblast (EVT) lineage formation and differentiation. However, restricted access to first trimester placentae requires alternative cell sources for establishing placental organoids. Recently, we demonstrated EVT differentiation in JEG-3-derived organoids. Consequently, we herein tested whether other commonly used trophoblastic cell lines, ACH-3P, HTR-8/SVneo, and SWAN-71 were capable of self-organizing into organoids and subsequent EVT differentiation. Notably, only ACH-3P formed organoids under stemness conditions mimicking TB-ORG architectures, and induction of EVT differentiation provoked formation of HLA-G areas. Hence ACH-3P-ORGs provide another organoid model for studying controlled EVT lineage formation and differentiation.
Topics: Pregnancy; Female; Humans; Trophoblasts; Placenta; Cell Line, Tumor; Pregnancy Trimester, First; Cell Differentiation; Organoids
PubMed: 36696785
DOI: 10.1016/j.placenta.2023.01.005 -
Materials Science & Engineering. C,... Apr 2019Scaffolds from healthy placentae offer advantages for tissue engineering with undamaged matrix, associated cytoprotective molecules, and embedded vessels for...
Scaffolds from healthy placentae offer advantages for tissue engineering with undamaged matrix, associated cytoprotective molecules, and embedded vessels for revascularization. As size disparities in human placenta and small recipients hamper preclinical studies, we studied alternative of bovine placentomes in smaller size ranges. Multiple cow placentomes were decellularized and anatomical integrity was analyzed. Tissue engineering used inbred donor rat livers. Placentomes were hepatized and immediately transplanted in rats with perfusion from portal vein and drainage into inferior vena cava. Cows yielded 99 ± 16 placentomes each. Of these, approximately 25% had 3 to 9 cm diameter and 7 to 63 ml volume, which was suitable for transplantation. After decellularization, angiography and casts documented 100% of vessels and vascular networks were well-perfused without disruptions or leaks. The residual matrix also remained intact for transplantation of placentomes. Perfusion in transplanted placentomes was maintained over up to 30 days. Liver tissue reassembled with restoration of hepatic acinar and sinusoidal structure. Transplanted tissue was intact without apoptosis, or necrosis. Hepatic functions were maintained. Preservation of hepatic homeostasis was verified by cytofluorimetric analysis of hepatocyte ploidy. The prevalence in healthy and transplanted liver of diploid, tetraploid and higher ploidy classes was similar with 57%, 41% and 2% versus 51%, 46.5% and 2.6%, respectively, p = 0.77, ANOVA. CONCLUSIONS: Cow placentomes will allow therapeutic development with disease models in small animals. This will also advance drug or toxicology studies. Portasystemic interposition of engineered liver will be particularly suitable for treating hepatic insufficiencies (metabolic, secretory or detoxification needs), including for children or smaller adults.
Topics: Animals; Cattle; Female; Freeze Drying; Liver; Liver Transplantation; Perfusion; Placenta; Portal Vein; Pregnancy; Rats, Inbred Lew; Tissue Engineering; Tissue Scaffolds; Vena Cava, Inferior
PubMed: 30678914
DOI: 10.1016/j.msec.2018.12.025 -
Placenta Jan 2021We sought to examine placentas enriched for trophoblast inclusions (TIs) in order to characterize, quantify, and examine the interrelations between subtypes of TIs to...
We sought to examine placentas enriched for trophoblast inclusions (TIs) in order to characterize, quantify, and examine the interrelations between subtypes of TIs to better understand their underlying biology. We examined a cohort of 600 placentas from deliveries between 20 and 43 weeks of gestation. Forty-five percent of the placentas had at least one TI in the two slides examined. Four percent of the placentas had 10 or more TIs and two placentas had more than 70 TIs. Four distinct TI subtypes were observed: inclusionoids (early forming inclusions), inclusions, calcified inclusions, and calcified bodies. We suggest this reflects a developmental trajectory of TI maturation, the timing of which might be useful when comparing TI expression to clinical outcomes.
Topics: Adult; Biomarkers; Calcinosis; Female; Gestational Age; Humans; Image Processing, Computer-Assisted; Inclusion Bodies; Placenta; Pregnancy; Pregnancy Outcome; Trophoblasts; Young Adult
PubMed: 33152642
DOI: 10.1016/j.placenta.2020.10.014 -
Medicine Aug 2023Preeclampsia is a pregnancy complication Aim of this study was to investigate expression of Beclin1 and tumor necrosis factor (TNF)-α in normotensive and preeclamptic...
BACKGROUND
Preeclampsia is a pregnancy complication Aim of this study was to investigate expression of Beclin1 and tumor necrosis factor (TNF)-α in normotensive and preeclamptic placentas of pregnant women patients.
METHODS
Twenty normotensive and 20 preeclamptic patients placentas were dissected for paraffin- wax processing. Placental samples were embedded in parafin blocks. Sections were stained with Hematoxylin-Eosin staining and TNF-α and Beclin1 immunostaining.
RESULTS
In control group, root and floating villi were normal in histological perspectives, syncytial node number was low, vessels were normal with connective tissue. No hemorrhage was observed in the intervillous area. In preeclampsia group, decidual cell degeneration and fibrinoid accumulation increased. Vascular dilatation and congestion with mononuclear cell infiltration were observed. Beclin1 reaction was generally negative in control group. In preeclampsia group, Beclin1 reaction was increased in decidual cells, syncytial nodes and bridges and in chorionic villi and in some Hoffbauer cells. In control group, TNF-α expression was mainly negative but only in some decidual cells. In preeclampsia, TNF-α reaction was observed in degenerated decidua cells, in leukocytes and in villi.
CONCLUSION
In preeclampsia placentas, degenerated decidua cells and inflammation increased. It was thought that Beclin1 and TNF-α signals could be used as a marker in affecting the fetal structure of blood flow in preeclamptic placentas.
Topics: Female; Humans; Pregnancy; Beclin-1; Chorionic Villi; Placenta; Pre-Eclampsia; Tumor Necrosis Factor-alpha
PubMed: 37603530
DOI: 10.1097/MD.0000000000034757