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PloS One 2011The uptake and trans-placental trafficking of fatty acids from the maternal blood into the fetal circulation are essential for embryonic development, and involve several...
BACKGROUND
The uptake and trans-placental trafficking of fatty acids from the maternal blood into the fetal circulation are essential for embryonic development, and involve several families of proteins. Fatty acid transport proteins (FATPs) uniquely transport fatty acids into cells. We surmised that placental FATPs are germane for fetal growth, and are regulated during hypoxic stress, which is associated with reduced fat supply to the fetus.
METHODOLOGY/PRINCIPAL FINDINGS
Using cultured primary term human trophoblasts we found that FATP2, FATP4 and FATP6 were highly expressed in trophoblasts. Hypoxia enhanced the expression of trophoblastic FATP2 and reduced the expression of FATP4, with no change in FATP6. We also found that Fatp2 and Fatp4 are expressed in the mouse amnion and placenta, respectively. Mice deficient in Fatp2 or Fatp4 did not deviate from normal Mendelian distribution, with both embryos and placentas exhibiting normal weight and morphology, triglyceride content, and expression of genes related to fatty acid mobilization.
CONCLUSIONS/SIGNIFICANCE
We conclude that even though hypoxia regulates the expression of FATP2 and FATP4 in human trophoblasts, mouse Fatp2 and Fatp4 are not essential for intrauterine fetal growth.
Topics: Animals; Cell Hypoxia; Coenzyme A Ligases; Fatty Acid Transport Proteins; Female; Gene Expression Regulation; Humans; Mice; Mutation; Placenta; Pregnancy; Trophoblasts
PubMed: 22028793
DOI: 10.1371/journal.pone.0025865 -
Journal of Biomedical Optics Nov 2020Placenta is an essential organ for fetal development and successful reproduction. Placental insufficiency can lead to fetal hypoxia and, in extreme cases anoxia, leading...
SIGNIFICANCE
Placenta is an essential organ for fetal development and successful reproduction. Placental insufficiency can lead to fetal hypoxia and, in extreme cases anoxia, leading to fetal death. Of the 145 million deliveries per year worldwide, ∼15 million neonates are small for gestational age and, therefore, at risk for antepartum and intrapartum hypoxia. Clinical methods to assess placental function largely rely on the assessment of fetal heart rate changes but do not assess placental oxygenation. Near-infrared spectroscopy (NIRS) allows non-invasive, real-time assessment of tissue oxygenation in intact organs, which can be used to assess placental oxygenation. However, tissue optical properties can affect the accuracy of methods to measure tissue oxygenation.
AIM
This study was performed to estimate the scattering coefficient of the human placenta. We have computed the scattering coefficients of the human placenta for the range of 659 to 840 nm using two methods of diffuse reflectance spectroscopy (DRS).
APPROACH
Measurements were performed using an in-house DRS device and a well-established frequency-domain diffuse optical spectroscopic system (DOSI). Measurements were performed in eight placentas obtained after cesarean deliveries. Placentas were perfused with normal saline to minimize the effects of absorption due to blood. Three sites per placenta were measured. Absorption and scattering coefficients were then calculated from the measured reflectance using the random walk theory for DRS and frequency-domain algorithm for DOSI.
RESULTS
Average reduced scattering coefficient (μs ' ) was 0.943 ± 0.015 mm - 1 at 760 nm and 0.831 ± 0.009 mm - 1 at 840 nm, and a power function μs ' = 1.6619 (λ/500 nm) - 1.426 was derived for the human placental scattering coefficient.
CONCLUSION
We report for the first time the scattering coefficient of the human placenta. This information can be used to assess baseline scattering and improve measurements of placental oxygen saturation with NIRS.
Topics: Algorithms; Female; Humans; Infant, Newborn; Optical Devices; Placenta; Pregnancy; Spectroscopy, Near-Infrared
PubMed: 33155452
DOI: 10.1117/1.JBO.25.11.116001 -
American Journal of Obstetrics and... Mar 2017Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with...
BACKGROUND
Failure of physiologic transformation of spiral arteries has been reported in preeclampsia, fetal growth restriction, fetal death, and spontaneous preterm labor with intact or ruptured membranes. Spiral arteries with failure of physiologic transformation are prone to develop atherosclerotic-like lesions of atherosis. There are striking parallels between preeclampsia and atherosclerotic disease, and between lesions of atherosis and atherosclerosis. Endothelial activation, identified by intercellular adhesion molecule-1 expression, is present in atherosclerotic-like lesions of heart transplantation, and is considered a manifestation of rejection. Similarly, endothelial activation/dysfunction has been implicated in the pathophysiology of atherosclerosis and preeclampsia. Intercellular adhesion molecule-1-overexpressing-activated endothelial cells are more resistant to trophoblast displacement than nonactivated endothelium, and may contribute to shallow spiral artery trophoblastic invasion in obstetrical syndromes having failure of physiologic transformation.
OBJECTIVE
We sought to determine whether failure of spiral artery physiologic transformation was associated with activation of interstitial extravillous trophoblasts and/or spiral artery endothelium and presence of acute atherosis in the placental basal plate.
STUDY DESIGN
A cross-sectional study of 123 placentas (19-42 weeks' gestation) obtained from normal pregnancies (n = 22), preterm prelabor rupture of membranes (n = 26), preterm labor (n = 23), preeclampsia (n = 27), intrauterine fetal death (n = 15), and small for gestational age (n = 10) was performed. Failure of spiral artery physiologic transformation and presence of cell activation was determined using immunohistochemistry of placental basal plates containing a median of 4 (minimum: 1; maximum: 9) vessels per placenta. Endothelial/trophoblast cell activation was defined by the expression of intercellular adhesion molecule-1. Investigators examining microscopic sections were blinded to clinical diagnosis. Pairwise comparisons among placenta groups were performed with Fisher exact test and Wilcoxon rank sum test using a Bonferroni-adjusted level of significance (.025).
RESULTS
We found that 87% (94/108) of placentas having spiral arteries with failure of physiologic transformation (actin-positive and cytokeratin-negative) in the basal plate, and 0% (0/15) of placentas having only spiral arteries with complete physiologic transformation (cytokeratin-positive and actin-negative), had arterial endothelial and/or interstitial extravillous trophoblasts reactive with the intercellular adhesion molecule-1 activation marker (P < .001). A significant correlation (R = 0.84) was found between expression of spiral artery endothelial and interstitial extravillous trophoblast intercellular adhesion molecule-1 (P < .001) in activated placentas. Lesions of atherosis were found in 31.9% (30/94) of placentas with complete and/or partial failure of physiologic transformation of spiral arteries that were intercellular adhesion molecule-1-positive, in none of the 14 placentas with failure of physiologic transformation that were intercellular adhesion molecule-1-negative, and in none of the 15 placentas with complete spiral artery physiologic transformation without failure (P = .001). All placentas (30/30, 100%) with atherosis were identified in placentas having concomitant spiral artery endothelial and interstitial extravillous trophoblast activation.
CONCLUSION
Failure of spiral artery physiologic transformation in the placental basal plate is associated with interstitial extravillous trophoblast and arterial endothelial activation along with increased frequency of spiral artery atherosis. These findings may be used to improve the characterization of different disorders of the placental bed such as in refining the existing tools for the early prediction of risk for preterm, preeclamptic, and other abnormal pregnancies.
Topics: Acute Disease; Arteries; Cross-Sectional Studies; Endothelium, Vascular; Female; Humans; Placenta; Pregnancy; Pregnancy Complications, Cardiovascular; Trophoblasts; Vascular Diseases
PubMed: 28034657
DOI: 10.1016/j.ajog.2016.12.029 -
Proceedings of the National Academy of... Apr 2006The placenta is the principal metabolic, respiratory, excretory, and endocrine organ for the first 9 months of fetal life. Its role in fetal and maternal physiology is...
The placenta is the principal metabolic, respiratory, excretory, and endocrine organ for the first 9 months of fetal life. Its role in fetal and maternal physiology is remarkably diverse. Because of the central role that the placenta has in fetal and maternal physiology and development, the possibility that variation in placental gene expression patterns might be linked to important abnormalities in maternal or fetal health, or even variations in later life, warrants investigation. As an initial step, we used DNA microarrays to analyze gene expression patterns in 72 samples of amnion, chorion, umbilical cord, and sections of villus parenchyma from 19 human placentas from successful full-term pregnancies. The umbilical cord, chorion, amnion, and villus parenchyma samples were readily distinguished by differences in their global gene-expression patterns, many of which seemed to be related to physiology and histology. Differentially expressed genes have roles that include placental trophoblast secretion, signal transduction, metabolism, immune regulation, cell adhesion, and structure. We found interindividual differences in expression patterns in villus parenchyma and systematic differences between the maternal, fetal, and intermediate layers. A group of genes that was expressed in both the maternal and fetal villus parenchyma sections of placenta included genes that may be associated with preeclampsia. We identified sets of genes whose expression in placenta was significantly correlated with the sex of the fetus. This study provides a rich and diverse picture of the molecular variation in the placenta from healthy pregnancies.
Topics: Female; Gene Expression; Humans; Male; Oligonucleotide Array Sequence Analysis; Placenta
PubMed: 16567644
DOI: 10.1073/pnas.0508035103 -
The Malaysian Journal of Pathology Jun 2010The placenta constitutes a physical and immunological barrier against infectious agents. Toll-like receptors (TLRs) are essential components for the induction of innate...
OBJECTIVE
The placenta constitutes a physical and immunological barrier against infectious agents. Toll-like receptors (TLRs) are essential components for the induction of innate immunity responses in different human tissues including the placenta. We investigated the expressions of TLR2 and TLR4 in the decidua and amniotic cells in non-inflamed placenta and placenta with infection.
MATERIALS AND METHODS
There were a total 74 placentas (37 with infection and 37 without infection- 25 bacterial, 10 viral and 2 toxoplasma). TLR2 and TLR4 expressions were assessed using immunohistochemical technique. Positive cells were indicated by cytoplasmic staining and the percentage of positive in 100 cells was recorded and graded. The grades were 1+ (< 25%), 2+ (25-75%) and 3+ (> 75%).
RESULTS
We found significantly higher expression of TLR2 in the amniotic cells and decidua cells in infected placentas as compared to non-inflamed placentas among the preterm placenta. A higher number of cases have TLR4 expression in the amnion of preterm infected placenta than in term placenta. This, however, is not statistically significant.
CONCLUSION
Our findings suggest that TLR2 plays a role in the innate immunity in bacterial and viral infection in the placenta, however, their role in protection against toxoplasma may be limited. This study further supports the observations that TLR2 expression was higher in placenta with infection which strengthened the role of TLR2 in the protection of preterm placenta against infection.
Topics: Chorioamnionitis; Female; Humans; Immunohistochemistry; Placenta; Pregnancy; Premature Birth; Retrospective Studies; Toll-Like Receptor 2; Toll-Like Receptor 4
PubMed: 20614721
DOI: No ID Found -
International Journal of Molecular... Jun 2021The road to low-dose aspirin therapy for the prevention of preeclampsia began in the 1980s with the discovery that there was increased thromboxane and decreased... (Review)
Review
The road to low-dose aspirin therapy for the prevention of preeclampsia began in the 1980s with the discovery that there was increased thromboxane and decreased prostacyclin production in placentas of preeclamptic women. At the time, low-dose aspirin therapy was being used to prevent recurrent myocardial infarction and other thrombotic events based on its ability to selectively inhibit thromboxane synthesis without affecting prostacyclin synthesis. With the discovery that thromboxane was increased in preeclamptic women, it was reasonable to evaluate whether low-dose aspirin would be effective for preeclampsia prevention. The first clinical trials were very promising, but then two large multi-center trials dampened enthusiasm until meta-analysis studies showed aspirin was effective, but with caveats. Low-dose aspirin was most effective when started <16 weeks of gestation and at doses >100 mg/day. It was effective in reducing preterm preeclampsia, but not term preeclampsia, and patient compliance and patient weight were important variables. Despite the effectiveness of low-dose aspirin therapy in correcting the placental imbalance between thromboxane and prostacyclin and reducing oxidative stress, some aspirin-treated women still develop preeclampsia. Alterations in placental sphingolipids and hydroxyeicosatetraenoic acids not affected by aspirin, but with biologic actions that could cause preeclampsia, may explain treatment failures. Consideration should be given to aspirin's effect on neutrophils and pregnancy-specific expression of protease-activated receptor 1, as well as additional mechanisms of action to prevent preeclampsia.
Topics: Animals; Aspirin; Biomarkers; Disease Management; Disease Susceptibility; Female; Gene Expression; Humans; Leukocytes; Placenta; Pre-Eclampsia; Pregnancy; Stromal Cells; Trophoblasts
PubMed: 34209594
DOI: 10.3390/ijms22136985 -
Autoimmunity Dec 2024Autoimmune diseases (AIDs) alter the placental immune environment leading to fetal loss. This study investigated the effects of AIDs on pregnancy and the placenta in...
Autoimmune diseases (AIDs) alter the placental immune environment leading to fetal loss. This study investigated the effects of AIDs on pregnancy and the placenta in AID-prone MRL/MpJ- mice and wild-type MRL/MpJ, which were mated with male MRL/MpJ and MRL/MpJ- at five months and defined as moLpr and moMpJ, respectively. AID indices (spleen weight and serum autoantibody levels) and fertility status (number and size of fetuses, morphology, and comprehensive gene expression of placentas) were evaluated on gestational day 15.5. Both strains showed equivalent fertility, but moLpr showed lighter placentas and fetuses than moMpJ, and decreased fertility with AID severity. moLpr placentas had a higher number of T cells, higher expression of genes associated with T helper 2 and T follicular helper functions, and altered expression of genes (, ) that significantly regulate pregnancy or immunity. The gene expression of T cell migration-associated chemokines (, ) was significantly increased in moLpr placentas, and CCL5 and CXCL9 were detected in moLpr placentas, particularly in T cells and placenta-component cells, respectively. Thus, AID altered placental morphofunction and fertility in mice; however, fertility was maintained at the examined time points. This study enhances our understanding of placental alterations and gestational risk due to AIDs.
Topics: Pregnancy; Mice; Female; Male; Animals; Mice, Inbred MRL lpr; Placenta; Autoimmune Diseases; T-Lymphocytes; Fertility; Amino Acid Transport Systems, Basic
PubMed: 38389171
DOI: 10.1080/08916934.2024.2319209 -
Placenta Apr 2018Bone marrow cells (BMC) from obese adult mice display an increased apoptosis rate over proliferation. Hematopoietic stem cells (HSC) form all blood cells and are...
INTRODUCTION
Bone marrow cells (BMC) from obese adult mice display an increased apoptosis rate over proliferation. Hematopoietic stem cells (HSC) form all blood cells and are important BMC used in cell therapy. Because it is known that prenatal development can be affected by adverse metabolic epigenetic programming from the maternal organism, this work aimed to investigate the effects of maternal overweight on placenta and fetal liver hematopoietic niches.
METHODS
Overweight was induced in female mice by overfeeding during lactation. After Swiss females were mated with healthy males, fetuses at 19 dpc (day post conception) and placentas were analyzed. Maternal biometric parameters were compared, and hematopoiesis in the dissociated placenta and fetal liver cells was analyzed by flow cytometry. Placenta morphology and protein content were also studied.
RESULTS
The model induced accumulation of adipose tissue, weight gain, and maternal hyperglycemia. Placentas from the overfed group (OG) displayed altered morphology, higher carbohydrate and lipid deposition, and increased protein content of fibronectin and PGC-1α. Cytometric analysis showed that placentas from OG presented a higher percentage of circulating macrophages, endothelial progenitor cells, HSC, and progenitor cells. No difference was detected in the percentage of neutrophil granulocytes and total leukocytes or in the proliferation of total cells, HSC, or total leukocytes. With regard to liver analysis of the OG group, there was a significant increase in circulating macrophages, primitive HSC, and oval cells but no difference in hematopoietic progenitor cells, total leukocytes, or leukocyte or total cell proliferation.
CONCLUSION
Unregulated maternal metabolism can affect hematopoietic populations within the placenta and fetal liver.
Topics: Animals; Animals, Newborn; Biometry; Female; Fetus; Hematopoiesis; Liver; Male; Mice; Overweight; Placenta; Pregnancy; Pregnancy Complications
PubMed: 29626983
DOI: 10.1016/j.placenta.2018.02.001 -
Biochemical and Biophysical Research... Sep 2022Preeclampsia (PE) is a multisystem progressive hypertensive disorder unique to human pregnancy. The placenta is fundamental to its pathogenesis and releases placental...
UNLABELLED
Preeclampsia (PE) is a multisystem progressive hypertensive disorder unique to human pregnancy. The placenta is fundamental to its pathogenesis and releases placental factors as well as extracellular vesicles (small and medium/large syncytiotrophoblast extracellular vesicles (STB-EVs)) as a response to syncytiotrophoblast stress such as tissue factor and plasminogen activator inhibitors 1. Neuropilin 1 (NRP-1) is an anti-angiogenic factor involved in development, angiogenesis, arteriogenesis, and vascular permeability. NRP-1 acts as a co-receptor for growth factors such as vascular endothelial growth factor (VEGF), placenta growth factor (PLGF), and epidermal growth factor (EGF). Given the documented pro and anti-angiogenic roles of STB-EVs, we hypothesized that 1) STB-EVs might express NRP-1; and 2) the expression of NRP-1 might differ between normal and preeclampsia STB-EVs.
METHODS
We isolated STB-EVs (both small and medium/large) from PE and NP placentae using the physiologic ex vivo dual lobe perfusion model. The enriched STB-EVs were characterized by Western blot, transmission electron microscopy (TEM), and nanoparticle tracking analysis (NTA) according to the international society of extracellular vesicles (ISEV) guidelines. We assessed for NRP-1 expression with Western blot (placenta and STB-EVs) and immunohistochemistry (placenta). We performed co-expression analysis for placenta alkaline phosphatase (PLAP - a known STB-EV marker) and NRP-1 with immunoprecipitation followed by Western blot.
RESULTS
We confirmed NRP-1 expression in NP and PE placenta. We showed that NRP-1 Expression was limited to small syncytiotrophoblast membrane extracellular vesicles (S STB-EVs) but not medium/large STB-EVs and that NRP-1 is co-expressed with PLAP.
CONCLUSION
Neuropilin-1 is uniquely expressed on small syncytiotrophoblast extracellular vesicles but not on medium/large vesicles from preeclampsia and normal placentae.
Topics: Extracellular Vesicles; Female; Humans; Neuropilin-1; Placenta; Pre-Eclampsia; Pregnancy; Trophoblasts; Vascular Endothelial Growth Factor A
PubMed: 35760012
DOI: 10.1016/j.bbrc.2022.06.041 -
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