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Seminars in Reproductive Medicine May 2011Normal function of the placenta is pivotal for optimal fetal growth and development. Fetal programming commonly is associated with placental dysfunction that predisposes... (Review)
Review
Normal function of the placenta is pivotal for optimal fetal growth and development. Fetal programming commonly is associated with placental dysfunction that predisposes to obstetric complications and suboptimal fetal outcomes. We consider several clinical phenotypes for placental dysfunction that likely predispose to fetal programming. Some of these reflect abnormal development of the chorioallantoic placenta in size, shape, or histopathology. Others result when exogenous stressors in the maternal environment combine with maladaptation of the placental response to yield small placentas with limited reserve, as typical of early-onset intrauterine growth restriction and preeclampsia. Still others reflect epigenetic changes, including altered expression of imprinted genes, altered enzymatic activity, or altered efficiencies in nutrient transport. Although the human placenta is a transient organ that persists only 9 months, the effects of this organ on the offspring remain for a lifetime.
Topics: Adult; Animals; Female; Fetal Development; Fetal Growth Retardation; Genomic Imprinting; Humans; Male; Maternal-Fetal Exchange; Organ Size; Placenta; Placenta Diseases; Placentation; Pre-Eclampsia; Pregnancy; Prenatal Exposure Delayed Effects
PubMed: 21710395
DOI: 10.1055/s-0031-1275515 -
PloS One 2019Plasmodium (P.) falciparum malaria during pregnancy has been frequently associated with severe consequences such as maternal anemia, abortion, premature birth, and...
Plasmodium (P.) falciparum malaria during pregnancy has been frequently associated with severe consequences such as maternal anemia, abortion, premature birth, and reduced birth weight. Placental damage promotes disruption of the local homeostasis; though, the mechanisms underlying these events are still to be elucidated. Autophagy is a fundamental homeostatic mechanism in the natural course of pregnancy by which cells self-recycle in order to survive in stressful environments. Placentas from non-infected and P. falciparum-infected women during pregnancy were selected from a previous prospective cohort study conducted in the Brazilian Amazon (Acre, Brazil). Newborns from infected women experienced reduced birth weight (P = 0.0098) and placental immunopathology markers such as monocyte infiltrate (P < 0.0001) and IL-10 production (P = 0.0122). The placentas were evaluated for autophagy-related molecules. As a result, we observed reduced mRNA levels of ULK1 (P = 0.0255), BECN1 (P = 0.0019), and MAP1LC3B (P = 0.0086) genes in placentas from P. falciparum-infected, which was more striking in those diagnosed with placental malaria. Despite the protein levels of these genes followed the same pattern, the observed reduction was not statistically significant in placentas from P. falciparum-infected women. Nevertheless, our data suggest that chronic placental immunopathology due to P. falciparum infection leads to autophagy dysregulation, which might impair local homeostasis during malaria in pregnancy that may result in poor pregnancy outcomes.
Topics: Adolescent; Adult; Autophagy; Down-Regulation; Female; Humans; Placenta; Plasmodium falciparum; Pregnancy; RNA, Messenger; Young Adult
PubMed: 31805150
DOI: 10.1371/journal.pone.0226117 -
Frontiers in Immunology 2021Since the beginning of the pandemic, few papers describe the placenta's morphological and morphometrical features in SARS-CoV-2-positive pregnant women. Alterations,...
UNLABELLED
Since the beginning of the pandemic, few papers describe the placenta's morphological and morphometrical features in SARS-CoV-2-positive pregnant women. Alterations, such as low placental weight, accelerated villous maturation, decidual vasculopathy, infarcts, thrombosis of fetal placental vessels, and chronic histiocytic intervillositis (CHI), have been described.
OBJECTIVE
To analyze clinical data and the placental morphological and morphometric changes of pregnant women infected with SARS-CoV-2 (COVID-19 group) in comparison with the placentas of non-infected pregnant women, matched for maternal age and comorbidities, besides gestational age of delivery (Control group).
METHOD
The patients in the COVID-19 and the Control group were matched for maternal age, gestational age, and comorbidities. The morphological analysis of placentas was performed using Amsterdam Placental Workshop Group Consensus Statement. The quantitative morphometric evaluation included perimeter diameter and number of tertiary villi, number of sprouts and knots, evaluation of deposition of villous fibrin, and deposition of intra-villous collagen I and III by Sirius Red. Additionally, Hofbauer cells (HC) were counted within villi by immunohistochemistry with CD68 marker.
RESULTS
Compared to controls, symptomatic women in the COVID-19 group were more likely to have at least one comorbidity, to evolve to preterm labor and infant death, and to have positive SARS-CoV-2 RNA testing in their concepts. Compared to controls, placentas in the COVID-19 group were more likely to show features of maternal and fetal vascular malperfusion. In the COVID-19 group, placentas of symptomatic women were more likely to show CHI. No significant results were found after morphometric analysis.
CONCLUSION
Pregnant women with symptomatic SARS-CoV-2 infection, particularly with the severe course, are more likely to exhibit an adverse fetal outcome, with slightly more frequent histopathologic findings of maternal and fetal vascular malperfusion, and CHI. The morphometric changes found in the placentas of the COVID-19 group do not seem to be different from those observed in the Control group, as far as maternal age, gestational age, and comorbidities are paired. Only the deposition of villous fibrin could be more accentuated in the COVID-19 group (p = 0.08 borderline). The number of HC/villous evaluated with CD68 immunohistochemistry did not show a difference between both groups.
Topics: Adult; Brazil; COVID-19; Case-Control Studies; Female; Gestational Age; Host-Pathogen Interactions; Humans; Immunohistochemistry; Infectious Disease Transmission, Vertical; Placenta; Pregnancy; Pregnancy Complications, Infectious; RNA, Viral; SARS-CoV-2; Viral Load
PubMed: 34122449
DOI: 10.3389/fimmu.2021.685919 -
The Journal of Clinical Endocrinology... Sep 2023Pregnant women with mutations in the thyroid hormone receptor beta (THRB) gene expose their fetuses to high thyroid hormone (TH) levels shown to be detrimental to a...
CONTEXT
Pregnant women with mutations in the thyroid hormone receptor beta (THRB) gene expose their fetuses to high thyroid hormone (TH) levels shown to be detrimental to a normal fetus (NlFe) but not to an affected fetus (AfFe). However, no information is available about differences in placental TH regulators.
OBJECTIVE
To investigate whether there are differences in placentas associated with a NlFe compared with an AfFe, we had the unique opportunity to study placentas from 2 pregnancies of the same woman with THRB mutation G307D. One placenta supported a NlFe while the other an AfFe.
METHODS
Sections of placentas were collected and frozen at -80 °C after term delivery of a NlFe and an AfFe. Two placentas from healthy women of similar gestational age were also obtained. The fetal origin of the placental tissues was established by gDNA quantitation of genes on the X and Y chromosomes and THRB gene. Expression and enzymatic activity of deiodinases 2 and 3 were measured. Expression of following genes was also quantitated: MCT10, MCT8, LAT1, LAT2, THRB, THRA.
RESULTS
The placenta carrying the AfFe exhibited a significant reduction of deiodinase 2 and 3 activities as well as the expression of the TH transporters MCT10, LAT1 and LAT2, and THRA.
CONCLUSION
We present the first study of the effect of the fetal THRB genotype on the placenta. Though limited by virtue of the rarity of THRB mutations and sample availability, we show that the fetal THRB genotype influences the levels of TH regulators in the placenta.
Topics: Female; Pregnancy; Humans; Placenta; Genes, erbA; Thyroid Hormone Receptors beta; Thyroid Hormones; Fetus; Genotype
PubMed: 37149816
DOI: 10.1210/clinem/dgad243 -
Placenta Nov 2021The mouse placenta accumulates and possibly produces serotonin (5-hydroxytryptamine; 5-HT) in parietal trophoblast giant cells (pTGC) located at the interface between...
INTRODUCTION
The mouse placenta accumulates and possibly produces serotonin (5-hydroxytryptamine; 5-HT) in parietal trophoblast giant cells (pTGC) located at the interface between the placenta and maternal deciduum. However, the roles of 5-HT in placental function are unclear. This lack of information is unfortunate, given that selective serotonin-reuptake inhibitors are commonly used to combat depression in pregnant women. The high affinity 5-HT transporter SLC6A4 (also known as SERT) is the target of such drugs and likely controls much of 5-HT uptake into pTGC and other placental cells. We hypothesized that ablation of the Slc6a4 gene would result in morphological changes correlated with placental gene expression changes, especially for those involved in nutrient acquisition and metabolism, and thereby, provide insights into 5-HT placental function.
METHODS
Placentas were collected at embryonic age (E) 12.5 from Slc6a4 knockout (KO) and wild-type (WT) conceptuses. Histological analyses, RNAseq, qPCR, and integrative correlation analyses were performed.
RESULTS
Slc6a4 KO placentas had a considerable increased pTGC to spongiotrophoblast area ratio relative to WT placentas and significantly elevated expression of genes associated with intestinal functions, including nutrient sensing, uptake, and catabolism, and blood clotting. Integrative correlation analyses revealed upregulation of many of these genes was correlated with pTGC layer expansion. One other key gene was dopa decarboxylase (Ddc), which catalyzes conversion of L-5-hydroxytryptophan to 5-HT.
DISCUSSION
Our studies possibly suggest a new paradigm relating to how 5-HT operates in the placenta, namely as a factor regulating metabolic functions and blood coagulation. We further suggest that pTGC might be functional analogs of enterochromaffin 5-HT-positive cells of the intestinal mucosa, which regulate similar activities within the gut. Further work, including proteomics and metabolomic studies, are needed to buttress our hypothesis.
Topics: Animals; Dopa Decarboxylase; Female; Giant Cells; Intestines; Mice; Mice, Inbred C57BL; Mice, Knockout; Placenta; Pregnancy; RNA; Sequence Analysis, RNA; Serotonin; Serotonin Plasma Membrane Transport Proteins; Trophoblasts; Up-Regulation
PubMed: 34649169
DOI: 10.1016/j.placenta.2021.09.021 -
Molecules (Basel, Switzerland) Sep 2021Animal placentae can be used as health-promoting food ingredients with various therapeutic efficacies, but their use is limited by their unpleasant odor and taste. This...
Animal placentae can be used as health-promoting food ingredients with various therapeutic efficacies, but their use is limited by their unpleasant odor and taste. This study aimed to investigate the possibility of deodorization of sheep placenta via yeast fermentation. A yeast strain was successfully isolated and identified as a novel strain ( kh3). The deodorizing efficacy of fermentation of the sheep placenta with kh3 was evaluated by 42 panels, based on evaluation of preference, ranking, and aroma profiles, and compared with normal placenta and placenta fermented with . The results of the sensory evaluation indicated that fermentation of the sheep placenta with kh3 may improve its palatability by increasing flavors such as that of grass (tree), rubber, and burnt, and by decreasing the odor and soy sauce flavor. Solid-phase microextraction-gas chromatography (SPME-GC) showed that major off-flavors in sheep placenta, such as ammonia, dimethyl disulfide, and 1,3-dioxolane, were completely diminished in the sheep placenta fermented with kh3. This study presents those major volatile compounds, including 2-isobutyl\-4,4-dimethyl-1,3-dioxane, and 3-methyl-1-butanol, could be crucial in improving the palatability of the sheep placentae fermented with kh3. This study provides a good starting point for the industrial application of a new deodorization method.
Topics: Animals; Brettanomyces; Female; Fermentation; Flavoring Agents; Gas Chromatography-Mass Spectrometry; Malus; Odorants; Placenta; Pregnancy; Sheep; Solid Phase Microextraction; Volatile Organic Compounds
PubMed: 34641377
DOI: 10.3390/molecules26195835 -
Annals of Nutrition & Metabolism 2017Gestational diabetes mellitus (GDM) is associated with increased fetal adiposity, which may increase the risk of obesity in adulthood. The placenta has insulin receptors... (Review)
Review
BACKGROUND
Gestational diabetes mellitus (GDM) is associated with increased fetal adiposity, which may increase the risk of obesity in adulthood. The placenta has insulin receptors and maternal insulin can activate its signaling pathways, affecting the transport of nutrients to the fetus. However, the effects of diet or insulin treatment on the placental pathophysiology of GDM are unknown.
SUMMARY
There are very few studies on possible defects in the insulin signaling pathway in the GDM placenta. Such defects could influence the placental transport of nutrients to the fetus. In this review we discuss the state of insulin signaling pathways in placentas of women with GDM, as well as the role of exogenous insulin in placental nutrient transport to the fetus, and fetal adiposity. Key Messages: Maternal insulin in the third trimester is correlated with fetal abdominal circumference at that time, suggesting the important role of insulin in this process. Since treatment with insulin at the end of pregnancy may activate placental nutrient transport to the fetus and promote placental fatty acid transfer, it would be interesting to improve maternal hyperlipidemia control in GDM subjects treated with this hormone. More research in this area with high number of subjects is necessary.
Topics: Birth Weight; Diabetes, Gestational; Female; Humans; Infant, Newborn; Insulin; Placenta; Pregnancy; Signal Transduction
PubMed: 28110332
DOI: 10.1159/000455904 -
Analyses of selected tumour-associated factors expression in normotensive and preeclamptic placenta.Pregnancy Hypertension Aug 2022Human placenta is often considered a controlled-tumour because of shared properties such as invasion and angiogenesis. We assessed the status of a few selected...
INTRODUCTION
Human placenta is often considered a controlled-tumour because of shared properties such as invasion and angiogenesis. We assessed the status of a few selected tumour-associated factors (TAFs) in late onset pre-eclamptic (PE) and normotensive (NT) placentae, to understand their involvement in trophoblast invasion. These molecules include aldehyde dehydrogenase (ALDH3A1), aurora kinases (AURK-A/C), platelet derived growth factor receptor-α (PDGFRα), jagged-1 (JAG1) and twist related protein-1 (TWIST1).
METHODS
The expression of TAF was compared in 13 NT and 11 PE (late onset) placentae using immunoblotting/immunohistochemistry. We then used a novel spheroidal cell model developed from transformed human first trimester trophoblast cell lines HTR8/SVneo and TEV-1 to determine the expression and localization of these six factors during invasion. We also compared the expression of these TAFs during migration and invasion.
RESULTS
Our results suggest that expressions of ALDH3A1, AURK-A, PDGFRα, and TWIST1 are significantly upregulated in PE placentae (p < 0.05) when compared to NT placentae, whereas AURK-C and JAG1 are down-regulated (p < 0.05). The protein expression pattern of all the six factors were found to be similar in spheroids in comparison to their parental counterparts. The invasive potential of the spheroids was also enhanced when compared with the parental cells.
DISCUSSION
Collectively, data from our present study suggests that these TAFs are involved in placental invasion and their altered expressions may be regarded as a compensatory mechanism against reduced invasion.
Topics: Female; Humans; Neoplasms; Placenta; Pre-Eclampsia; Pregnancy; Receptor, Platelet-Derived Growth Factor alpha; Trophoblasts
PubMed: 35717832
DOI: 10.1016/j.preghy.2022.06.001 -
Diabetes & Vascular Disease Research 2023Microvascular morphology and pathological changes in gestational diabetes mellitus (GDM) placentas and normal placentas were observed via vascular casting technology,...
AIMS
Microvascular morphology and pathological changes in gestational diabetes mellitus (GDM) placentas and normal placentas were observed via vascular casting technology, electron microscopy, and pathological detection technology. Vascular structure and histological morphology changes in GDM placentas were examined to generate basic experimental data for the diagnosis and prognostic determination of GDM.
METHODS
This case-control study involving 60 placentas, 30 from healthy controls and 30 from patients with GDM. Differences in size, weight, volume, umbilical cord diameter, and gestational age were assessed. Histological changes in the placentas in the two groups were analyzed and compared. A placental vessel casting model was constructed using a self-setting dental powder technique, to compare the two groups. The placental cast microvessels of the two groups were compared using scanning electron microscopy.
RESULTS
There were no significant differences in maternal age or gestational age between the GDM group and the control group ( > .05). The size, weight, volume, and thickness of the placentas in the GDM group were significantly greater than those in the control group, as was umbilical cord diameter ( < .05). Immature villus, fibrinoid necrosis, calcification, and vascular thrombosis were significantly greater in the placental mass in the GDM group ( < .05). The terminal branches of the microvessels in diabetic placenta casts were sparse, with significantly fewer ends and lower villous volume ( < .05).
CONCLUSION
Gestational diabetes can cause gross and histological changes in the placenta, particularly placental microvascular changes.
Topics: Pregnancy; Humans; Female; Placenta; Case-Control Studies; Diabetes, Gestational; Gestational Age
PubMed: 37186815
DOI: 10.1177/14791641231173627 -
American Journal of Physiology.... May 2012The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and... (Randomized Controlled Trial)
Randomized Controlled Trial
The human placenta is key to pregnancy outcome, and the elevated oxidative stress present in many complicated pregnancies contributes to placental dysfunction and suboptimal pregnancy outcomes. We tested the hypothesis that pomegranate juice, which is rich in polyphenolic antioxidants, limits placental trophoblast injury in vivo and in vitro. Pregnant women with singleton pregnancies were randomized at 35∼38 wk gestation to 8 oz/day of pomegranate juice or apple juice (placebo) until the time of delivery. Placental tissues from 12 patients (4 in the pomegranate group and 8 in the control group) were collected for analysis of oxidative stress. The preliminary in vivo results were extended to oxidative stress and cell death assays in vitro. Placental explants and cultured primary human trophoblasts were exposed to pomegranate juice or glucose (control) under defined oxygen tensions and chemical stimuli. We found decreased oxidative stress in term human placentas from women who labored after prenatal ingestion of pomegranate juice compared with apple juice as control. Moreover, pomegranate juice reduced in vitro oxidative stress, apoptosis, and global cell death in term villous explants and primary trophoblast cultures exposed to hypoxia, the hypoxia mimetic cobalt chloride, and the kinase inhibitor staurosporine. Punicalagin, but not ellagic acid, both prominent polyphenols in pomegranate juice, reduced oxidative stress and stimulus-induced apoptosis in cultured syncytiotrophoblasts. We conclude that pomegranate juice reduces placental oxidative stress in vivo and in vitro while limiting stimulus-induced death of human trophoblasts in culture. The polyphenol punicalagin mimics this protective effect. We speculate that antenatal intake of pomegranate may limit placental injury and thereby may confer protection to the exposed fetus.
Topics: Antioxidants; Apoptosis; Beverages; Cells, Cultured; Female; Humans; Hydrolyzable Tannins; In Vitro Techniques; Lythraceae; Oxidative Stress; Placenta; Polyphenols; Pregnancy; Trophoblasts
PubMed: 22374759
DOI: 10.1152/ajpendo.00003.2012