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The Journal of Maternal-fetal &... Dec 2023Ultrasound is key to evaluating placental function. However, traditional ultrasound examinations cannot evaluate the changes in the biomechanical properties of the... (Review)
Review
Ultrasound is key to evaluating placental function. However, traditional ultrasound examinations cannot evaluate the changes in the biomechanical properties of the placenta in vivo. As a non-invasive technique, shear wave elastography (SWE) can be used analyze the physiological and biomechanical properties of the placenta. Moreover, it can evaluate the pathological changes in early placental insufficiency in a more direct and sensitive manner. This study aimed to systematically introduce SWE in placental function evaluations. The terms 'placenta', 'ultrasound', and 'elastography' were searched on Pubmed, Embase, and CNKI databases (Apr 2023); this review was limited to results including placental sonoelastography. Twenty-six studies satisfied the inclusion criteria and were included in this review. Herein, we introduce the basic principle of SWE, analyze the factors affecting placental measurements, and summarize the prospects of clinical applications of SWE in the field of obstetrical diseases. The SWE technology demonstrates excellent clinical application value and research prospects in obstetrics, particularly in placental function evaluation, owing to its objective and repeatable quantitative operation.
Topics: Pregnancy; Humans; Female; Elasticity Imaging Techniques; Placenta; Ultrasonography
PubMed: 37121902
DOI: 10.1080/14767058.2023.2203792 -
Diabetologia Dec 2023Metformin is increasingly used therapeutically during pregnancy worldwide, particularly in the treatment of gestational diabetes, which affects a substantial proportion...
AIMS/HYPOTHESIS
Metformin is increasingly used therapeutically during pregnancy worldwide, particularly in the treatment of gestational diabetes, which affects a substantial proportion of pregnant women globally. However, the impact on placental metabolism remains unclear. In view of the association between metformin use in pregnancy and decreased birthweight, it is essential to understand how metformin modulates the bioenergetic and anabolic functions of the placenta.
METHODS
A cohort of 55 placentas delivered by elective Caesarean section at term was collected from consenting participants. Trophoblasts were isolated from the placental samples and treated in vitro with clinically relevant doses of metformin (0.01 mmol/l or 0.1 mmol/l) or vehicle. Respiratory function was assayed using high-resolution respirometry to measure oxygen concentration and calculated [Formula: see text]. Glycolytic rate and glycolytic stress assays were performed using Agilent Seahorse XF assays. Fatty acid uptake and oxidation measurements were conducted using radioisotope-labelled assays. Lipidomic analysis was conducted using LC-MS. Gene expression and protein analysis were performed using RT-PCR and western blotting, respectively.
RESULTS
Complex I-supported oxidative phosphorylation was lower in metformin-treated trophoblasts (0.01 mmol/l metformin, 61.7% of control, p<0.05; 0.1 mmol/l metformin, 43.1% of control, p<0.001). The proton efflux rate arising from glycolysis under physiological conditions was increased following metformin treatment, up to 23±5% above control conditions following treatment with 0.1 mmol/l metformin (p<0.01). There was a significant increase in triglyceride concentrations in trophoblasts treated with 0.1 mmol/l metformin (p<0.05), particularly those of esters of long-chain polyunsaturated fatty acids. Fatty acid oxidation was reduced by ~50% in trophoblasts treated with 0.1 mmol/l metformin compared with controls (p<0.001), with no difference in uptake between treatment groups.
CONCLUSIONS/INTERPRETATION
In primary trophoblasts derived from term placentas metformin treatment caused a reduction in oxidative phosphorylation through partial inactivation of complex I and potentially by other mechanisms. Metformin-treated trophoblasts accumulate lipids, particularly long- and very-long-chain polyunsaturated fatty acids. Our findings raise clinically important questions about the balance of risk of metformin use during pregnancy, particularly in situations where the benefits are not clear-cut and alternative therapies are available.
Topics: Humans; Female; Pregnancy; Placenta; Metformin; Trophoblasts; Cesarean Section; Fatty Acids; Fatty Acids, Unsaturated
PubMed: 37670017
DOI: 10.1007/s00125-023-05996-3 -
Frontiers in Immunology 2024The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced the placenta as the major anatomical site to provide... (Review)
Review
The transition from oviparity to viviparity and the establishment of feto-maternal communications introduced the placenta as the major anatomical site to provide nutrients, gases, and hormones to the developing fetus. The placenta has endocrine functions, orchestrates maternal adaptations to pregnancy at different periods of pregnancy, and acts as a selective barrier to minimize exposure of developing fetus to xenobiotics, pathogens, and parasites. Despite the fact that this ancient organ is central for establishment of a normal pregnancy in eutherians, the placenta remains one of the least studied organs. The first step of pregnancy, embryo implantation, is finely regulated by the trophoectoderm, the precursor of all trophoblast cells. There is a bidirectional communication between placenta and endometrium leading to decidualization, a critical step for maintenance of pregnancy. There are three-direction interactions between the placenta, maternal immune cells, and the endometrium for adaptation of endometrial immune system to the allogeneic fetus. While 65% of all systemically expressed human proteins have been found in the placenta tissues, it expresses numerous placenta-specific proteins, whose expression are dramatically changed in gestational diseases and could serve as biomarkers for early detection of gestational diseases. Surprisingly, placentation and carcinogenesis exhibit numerous shared features in metabolism and cell behavior, proteins and molecular signatures, signaling pathways, and tissue microenvironment, which proposes the concept of "cancer as ectopic trophoblastic cells". By extensive researches in this novel field, a handful of cancer biomarkers has been discovered. This review paper, which has been inspired in part by our extensive experiences during the past couple of years, highlights new aspects of placental functions with emphasis on its immunomodulatory role in establishment of a successful pregnancy and on a potential link between placentation and carcinogenesis.
Topics: Humans; Pregnancy; Female; Placenta; Animals; Placentation; Endometrium; Neoplasms; Embryo Implantation
PubMed: 38707901
DOI: 10.3389/fimmu.2024.1385762 -
FASEB Journal : Official Publication of... Dec 2023Glucose metabolism is vital to the survival of living organisms. Since the discovery of the Warburg effect in the 1920s, glycolysis has become a major research area in... (Review)
Review
Glucose metabolism is vital to the survival of living organisms. Since the discovery of the Warburg effect in the 1920s, glycolysis has become a major research area in the field of metabolism. Glycolysis has been extensively studied in the field of cancer and is considered as a promising therapeutic target. However, research on the role of glycolysis in pregnancy is limited. Recent evidence suggests that blastocysts, trophoblasts, decidua, and tumors all acquire metabolic energy at specific stages in a highly similar manner. Glycolysis, carefully controlled throughout pregnancy, maintains a dynamic and coordinated state, so as to maintain the homeostasis of the maternal-fetal interface and ensure normal gestation. In the present review, we investigate metabolic remodeling and the selective propensity of the embryo and placenta for glycolysis. We then address dysregulated glycolysis that occurs in the cellular interactive network at the maternal-fetal interface in miscarriage, preeclampsia, fetal growth restriction, and gestational diabetes mellitus. We provide new insights into the field of maternal-fetal medicine from a metabolic perspective, thus revealing the mystery of human pregnancy.
Topics: Pregnancy; Female; Humans; Decidua; Placenta; Trophoblasts; Abortion, Spontaneous; Glycolysis
PubMed: 37889786
DOI: 10.1096/fj.202301230R -
Environmental Research Jul 2023Placenta mediates the transfer of nutrients, oxygen and drugs from mother to fetus. It is constituted by two cellular layers separated by the intervillous space: the...
Placenta mediates the transfer of nutrients, oxygen and drugs from mother to fetus. It is constituted by two cellular layers separated by the intervillous space: the outer is in direct contact with maternal blood (decidua placenta), and the inner (villi) directly in contact with the fetus. Environmental contaminants, such as per- and polyfluoroalkyl substances (PFAS) also demonstrated the ability to cross the tissue multiple layers, posing at risk the health of the fetus. The aim of the present study was to analyse the PFAS amount in decidua and villi placenta explants and to study differences in their distribution among the two side of this organ. The determination of 23 PFAS was carried out by liquid chromatography coupled to high-resolution accurate mass spectrometry (LC-HRAM). Our research included women who delivered at term between 2021 and 2022. Our data indicated that all samples contained at least one PFAS, demonstrating the ubiquitarian presence of these compounds in our population. A high occurrence of PFOS, PFOA and PFHxS, followed by PFHxA, PFBS and PFUnA was found. The fluorotelomer 6:2 FTS was also present in more than 40% of samples and this represent the first data on placenta explants. Mean and median PFAS values for decidual explants were 0.5 ng/g and 0.4 ng/g (SD 0.3), while for villi explants mean and median values were 0.6 ng/g and 0.4 ng/g (SD 0.4). A different pattern of accumulation was observed between villi and decidual explants for PFOS, PFOA and PFUnA (villi > decidua) and PFHxA, PFHxS, PFBS and 6:2 FTS (decidua > villi). Even if the mechanism of this selectively accumuation is not yet understood, molecular degree of ionization and its lipophilicity could at least in part explain this difference. This study expands the limited data describing PFAS levels in the placenta and pose attention on PFAS exposure during pregnancy.
Topics: Pregnancy; Humans; Female; Placenta; Fluorocarbons; Mothers; Decidua; Alkanesulfonic Acids; Environmental Pollutants
PubMed: 37119845
DOI: 10.1016/j.envres.2023.115955 -
The Indian Journal of Medical Research Oct 2023Pre-eclampsia (PE), a multifactorial de novo hypertensive pregnancy disorder, is one of the leading causes of foeto-maternal morbidity and mortality. Currently,... (Review)
Review
Pre-eclampsia (PE), a multifactorial de novo hypertensive pregnancy disorder, is one of the leading causes of foeto-maternal morbidity and mortality. Currently, antihypertensive drugs are the first-line therapy for PE and evidence suggests that low-dose aspirin initiated early in high risk pregnancies may reduce the risk of development or severity of PE. However, an early prediction of this disorder remains an unmet clinical challenge. Several potential serum biomarkers associated with maternal immunoregulation and placental angiogenesis have been evaluated but are ineffective and inconsistent for early prediction. Although placental biomarkers would be more specific and sensitive in predicting the risk of PE, accessing the placenta during pregnancy is not feasible. Circulating placental exosomes (pEXO), originating from foeto-maternal interface, are being evaluated as the placenta's surrogate and the best source of non-invasive placental biomarkers. pEXO appear in the maternal circulation starting from six weeks of gestation and its dynamic biological cargo across pregnancy is associated with successful pregnancy outcomes. Therefore, monitoring changes in pEXO expression profiles could provide new insights into the prediction, diagnosis and treatment of PE. This narrative review comprehensively summarizes the available literature on the candidate predictive circulating biomarkers evaluated for PE to date. In particular, the review elucidates the current knowledge of distinct molecular signatures emanating from pEXO in pre-eclamptic women to support the discovery of novel early predictive biomarkers for effective intervention and management of the disease.
Topics: Pregnancy; Female; Humans; Placenta; Pre-Eclampsia; Exosomes; Pregnancy Outcome; Biomarkers; Hypertension
PubMed: 37987999
DOI: 10.4103/ijmr.ijmr_2143_22 -
Physiological Reports Jun 2024Physical activity (PA) positively influences pregnancy, a critical period for health promotion, and affects placental structure and function in ways previously... (Review)
Review
Physical activity (PA) positively influences pregnancy, a critical period for health promotion, and affects placental structure and function in ways previously overlooked. Here, we summarize the current body of literature examining the association between PA, placenta biology, and physiology while also highlighting areas where gaps in knowledge exist. PA during pregnancy induces metabolic changes, influencing nutrient availability and transporter expression in the placenta. Hormones and cytokines secreted during PA contribute to health benefits, with intricate interactions in pro- and anti-inflammatory markers. Extracellular vesicles and placental "-omics" data suggest that gestational PA can shape placental biology, affecting gene expression, DNA methylation, metabolite profiles, and protein regulation. However, whether cytokines that respond to PA alter placental proteomic profiles during pregnancy remains to be elucidated. The limited research on placenta mitochondria of physically active gestational parents (gesP), has shown improvements in mitochondrial DNA and antioxidant capacity, but the relationship between PA, placental mitochondrial dynamics, and lipid metabolism remains unexplored. Additionally, PA influences the placenta-immune microenvironment, angiogenesis, and may confer positive effects on neurodevelopment and mental health through placental changes, vascularization, and modulation of brain-derived neurotrophic factor. Ongoing exploration is crucial for unraveling the multifaceted impact of PA on the intricate placental environment.
Topics: Humans; Female; Pregnancy; Placenta; Exercise; Animals
PubMed: 38872466
DOI: 10.14814/phy2.16104 -
Placenta Mar 2024Placental phospholipid synthesis is critical for the expansion of the placental exchange surface area and for production of signaling molecules. Despite their...
INTRODUCTION
Placental phospholipid synthesis is critical for the expansion of the placental exchange surface area and for production of signaling molecules. Despite their importance, it is not yet established which enzymes involved in the de novo synthesis and remodeling of placental phospholipids are expressed and active in the human placenta.
METHODS
We identified phospholipid synthesis enzymes by immunoblotting in placental homogenates and immunofluorescence in placenta tissue sections. Primary human trophoblast (PHT) cells from term healthy placentas (n = 10) were cultured and exposed to C labeled fatty acids (16:0, 18:1 and 18:2 n-6, 22:6 n-3) for 2 and 24 h. Three phospholipid classes; phosphatidic acid, phosphatidylcholine, and lysophosphatidylcholine containing C fatty acids were quantified by Liquid Chromatography with tandem mass spectrometry (LC/MS-MS).
RESULTS
Acyl transferase and phospholipase enzymes were detected in human placenta homogenate and primarily expressed in the syncytiotrophoblast. Three representative C fatty acids (16:0, 18:1 and 18:2 n-6) were incorporated rapidly into phosphatidic acid in trophoblasts, but C labeled docosahexaenoic acid (DHA; 22:6 n-3) incorporation was not detected. C DHA was incorporated into phosphatidylcholine. Lysophosphatidylcholine containing all four C labeled fatty acids were found in high abundance.
CONCLUSIONS
Phospholipid synthesis and remodeling enzymes are present in the syncytiotrophoblast. C labeled fatty acids were rapidly incorporated into cellular phospholipids. C DHA was incorporated into phospholipids through the remodeling pathway rather than by de novo synthesis. These understudied pathways are highly active and critical for structure and function of the placenta.
Topics: Humans; Pregnancy; Female; Placenta; Phospholipids; Lysophosphatidylcholines; Fatty Acids; Phosphatidylcholines
PubMed: 38278000
DOI: 10.1016/j.placenta.2024.01.007 -
Placenta Dec 2023Obesity in pregnancy is associated with adverse long-term consequences both in the mother and in offspring. Maternal obesity induces a metabolic-inflammatory state that...
INTRODUCTION
Obesity in pregnancy is associated with adverse long-term consequences both in the mother and in offspring. Maternal obesity induces a metabolic-inflammatory state that could impact on placental function and could mediate the adverse outcomes. The purpose of this study was to compare the major placental histological characteristics of non-diabetic obese women to lean controls, focusing on uncomplicated pregnancies.
METHODS
Prospective case-control study comparing placental histopathological features between 122 non-diabetic obese women and 185 non-obese controls. The analysis was performed on overall subjects, then uncomplicated pregnancies from both groups were analyzed. Placenta pathologic findings were recorded according to standard classification.
RESULTS
Both in overall analysis and among the subset of subjects with an uncomplicated pregnancy, obese subjects had higher risks of maternal vascular malperfusion (MVM) (respectively OR=2.2, 95%CI =1.3-3.7 and OR=4.2, 95%CI=2.1-8.5), fetal vascular malperfusion (FVM) (respectively OR=6.3, 95%CI=3.1-12.5 and OR=7.2, 95%CI=3-17.2), maternal and fetal inflammatory response placental lesions and villitis (VUE) (respectively OR=2.5, 95%CI=1.1-5.6 and OR=10.8, 95%CI=3.3-35.3) compared to controls. Among uncomplicated pregnancies and after adjustment for confounders, first trimester BMI was significantly associated with overall MVM, overall FVM, maternal inflammatory, fetal inflammatory response and VUE.
DISCUSSION
Placentas from obese women showed a significantly higher risk of maternal and fetal vascular and inflammatory placental lesions, both in overall population and in the subgroup with uncomplicated pregnancies. The metabolic and inflammatory dysfunctions typical of obesity could have an impact on placental development and function, which could be a mediator of the detrimental effects of obesity on pregnancy outcome and on future health of the offspring.
Topics: Pregnancy; Female; Humans; Placenta; Case-Control Studies; Pregnancy Outcome; Placenta Diseases; Obesity
PubMed: 37922644
DOI: 10.1016/j.placenta.2023.10.011 -
Science Advances Mar 2024Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion...
Studying placental functions is crucial for understanding pregnancy complications. However, imaging placenta is challenging due to its depth, volume, and motion distortions. In this study, we have developed an implantable placenta window in mice that enables high-resolution photoacoustic and fluorescence imaging of placental development throughout the pregnancy. The placenta window exhibits excellent transparency for light and sound. By combining the placenta window with ultrafast functional photoacoustic microscopy, we were able to investigate the placental development during the entire mouse pregnancy, providing unprecedented spatiotemporal details. Consequently, we examined the acute responses of the placenta to alcohol consumption and cardiac arrest, as well as chronic abnormalities in an inflammation model. We have also observed viral gene delivery at the single-cell level and chemical diffusion through the placenta by using fluorescence imaging. Our results demonstrate that intravital imaging through the placenta window can be a powerful tool for studying placenta functions and understanding the placental origins of adverse pregnancy outcomes.
Topics: Pregnancy; Female; Mice; Animals; Placenta; Placentation; Microscopy; Optical Imaging; Intravital Microscopy
PubMed: 38507481
DOI: 10.1126/sciadv.adk1278