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The Journal of Reproduction and... Jun 2019Preeclampsia is a systemic disease caused by abnormal placentation that affects both mother and fetus. It was reported that Laeverin (LVRN, also known as Aminopeptidase...
Preeclampsia is a systemic disease caused by abnormal placentation that affects both mother and fetus. It was reported that Laeverin (LVRN, also known as Aminopeptidase Q) was up-regulated in the placenta of preeclamptic patients. However, physiological and pathological functions of LVRN remained to be unknown. Here we characterized Lvrn function during placentation in mice. RT-PCR showed that Lvrn is expressed in both fetus and placenta during embryogenesis, and several adult tissues. When we overexpressed Lvrn in a placenta-specific manner using lentiviral vectors, we did not see any defects in both placentae and fetuses. The mice carrying Lvrn overexpressing placentas did not show any preeclampsia-like symptoms such as maternal high blood pressure and fetal growth restriction. We next ablated Lvrn by CRISPR/Cas9-mediated genome editing to see physiological function. In Lvrn ablated mice, maternal blood pressure during pregnancy was not affected, and both placentas and fetuses grew normally. Collectively, these results suggest that, LVRN is irrelevant to preeclampsia and dispensable for normal placentation and embryonic development in mice.
Topics: Animals; Blood Pressure; CRISPR-Cas Systems; Female; Fetal Growth Retardation; Fetus; Gene Expression Profiling; Gene Expression Regulation, Developmental; Lentivirus; Metalloproteases; Mice; Mice, Knockout; Placenta; Placentation; Pre-Eclampsia; Pregnancy; Pregnancy, Animal; Trophoblasts
PubMed: 30745494
DOI: 10.1262/jrd.2018-157 -
International Journal of Molecular... Dec 2022As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a...
As the mediator between the mother and fetus, the placenta allows the most appropriate environment and optimal fetal growth. The placenta of one sex sometimes has a greater ability over the other to respond to and protect against possible maternal insults. Here, we characterized sex differences in the placenta’s morphological features and antioxidant status following dexamethasone (Dx) exposure. Pregnant rats were exposed to Dx or saline. The placenta was histologically and stereologically analyzed. The activity of the antioxidant enzymes, lipid peroxides (TBARS), superoxide anion and nitric oxide (NO) was measured. The decrease in placental zone volumes was more pronounced (p < 0.05) in female placentas. The volume density of PCNA-immunopositive nuclei was reduced (p < 0.05) in both sexes. The reduced (p < 0.05) antioxidant enzyme activities, enhanced TBARS and NO concentration indicate that Dx exposure triggered oxidative stress in the placenta of both fetal sexes, albeit stronger in the placenta of female fetuses. In conclusion, maternal Dx treatment reduced the size and volume of placental zones, altered placental histomorphology, decreased cell proliferation and triggered oxidative stress; however, the placentas of female fetuses exerted more significant responses to the treatment effects. The reduced placental size most probably reduced the transport of nutrients and oxygen, thus resulting in the reduced weight of fetuses, similar in both sexes. The lesser ability of the male placenta to detect and react to maternal exposure to environmental challenges may lead to long-standing health effects.
Topics: Animals; Female; Male; Pregnancy; Rats; Antioxidants; Dexamethasone; Maternal Exposure; Oxidation-Reduction; Placenta; Thiobarbituric Acid Reactive Substances
PubMed: 36613982
DOI: 10.3390/ijms24010540 -
Journal of Magnetic Resonance Imaging :... Jul 2022Advanced magnetic resonance imaging (MRI) methods are increasingly being used to assess the human placenta. Yet, the structure-function interplay in normal placentas and...
BACKGROUND
Advanced magnetic resonance imaging (MRI) methods are increasingly being used to assess the human placenta. Yet, the structure-function interplay in normal placentas and their associations with pregnancy risks are not fully understood.
PURPOSE
To characterize the normal human placental structure (volume and umbilical cord centricity index (CI)) and function (perfusion) ex-vivo using MRI, to assess their association with birth weight (BW), and identify imaging-markers for placentas at risk for dysfunction.
STUDY TYPE
Prospective.
POPULATION
Twenty normal term ex-vivo placentas.
FIELD STRENGTH/SEQUENCE
3 T/ T and T weighted (T W, T W) turbo spin-echo, three-dimensional susceptibility-weighted image, and time-resolved angiography with interleaved stochastic trajectories (TWIST), during passage of a contrast agent using MRI compatible perfusion system that mimics placental flow.
ASSESSMENT
Placental volume and CI were manually extracted from the T W images by a fetal-placental MRI scientist (D.L., 7 years of experience). Perfusion maps including bolus arrival-time and full-width at half maximum were calculated from the TWIST data. Mean values, entropy, and asymmetries were calculated from each perfusion map, relating to both the whole placenta and volumes of interest (VOIs) within the umbilical cord and its daughter blood vessels.
STATISTICAL TESTS
Pearson correlations with correction for multiple comparisons using false discovery rate were performed between structural and functional parameters, and with BW, with P < 0.05 considered significant.
RESULTS
All placentas were successfully perfused and scanned. Significant correlations were found between whole placenta and VOIs perfusion parameters (mean R = 0.76 ± 0.06, range = 0.67-0.89), which were also significantly correlated with CI (mean R = 0.72 ± 0.05, range = 0.65-0.79). BW was correlated with placental volume (R = 0.62), but not with CI (P = 0.40). BW was also correlated with local perfusion asymmetry (R = -0.71).
DATA CONCLUSION
Results demonstrate a gradient of placental function, associated with CI and suggest several ex-vivo imaging-markers that might indicate an increased risk for placental dysfunction.
LEVEL OF EVIDENCE
1 TECHNICAL EFFICACY: Stage 1.
Topics: Birth Weight; Contrast Media; Female; Humans; Magnetic Resonance Imaging; Placenta; Pregnancy; Prospective Studies
PubMed: 34799945
DOI: 10.1002/jmri.28002 -
Placenta Jan 2016Do monochorionic (MC) and/or dichorionic (DC) twins show allometric scaling between placental and birth weight (PW, BW)?
OBJECTIVE
Do monochorionic (MC) and/or dichorionic (DC) twins show allometric scaling between placental and birth weight (PW, BW)?
METHODS
We extracted BW, PW, gestational age (GA) and cord insertion type from 52 MC to 310 DC twins to calculate β. DC twins were analyzed as summed and as individuals if placentas were separate.
RESULTS
Mean β for MC (0.78 ± 0.02), DC summed (0.78 ± 0.02), and DC with separate placentas (0.77 ± 0.03 and 0.76 ± 0.04) all non-significant. GA, summed BWs, total PW, BW discordance, and cord insertion sites did not differ between twin types or with β.
CONCLUSION
MC and DC twins show allometric scaling similar to singletons.
Topics: Birth Weight; Energy Metabolism; Female; Fetal Development; Fetal Growth Retardation; Fetal Weight; Humans; Infant, Newborn; Organ Size; Placenta; Pregnancy; Pregnancy, Twin; Twins, Dizygotic; Twins, Monozygotic
PubMed: 26748158
DOI: 10.1016/j.placenta.2015.11.010 -
Evolution; International Journal of... Jan 2024The placenta mediates physiological exchange between the mother and the fetus. In placental mammals, all placentas are descended from a single common ancestor and... (Review)
Review
The placenta mediates physiological exchange between the mother and the fetus. In placental mammals, all placentas are descended from a single common ancestor and functions are conserved across species; however, the placenta exhibits radical structural diversity. The selective pressures behind this structural diversity are poorly understood. Traditionally, placental structures have largely been investigated by grouping them into qualitative categories. Assessing the placenta on this basis could be problematic when inferring the relative "efficiency" of a placental configuration to transfer nutrients from mother to fetus. We argue that only by considering placentas as three-dimensional (3D) biological structures, integrated across scales, can the evolutionary questions behind their enormous structural diversity be quantitatively determined. We review the current state of placental evolution from a structural perspective, detail where 3D imaging and computational modeling have been used to gain insight into placental function, and outline an experimental roadmap to answer evolutionary questions from a multiscale 3D structural perspective. Our approach aims to shed light on placental evolution, and can be transferred to evolutionary investigations in any organ system.
Topics: Animals; Pregnancy; Female; Placenta; Computer Simulation; Mammals
PubMed: 37974468
DOI: 10.1093/evolut/qpad209 -
Placenta Sep 2020We aim to examine the location of the vascular equator according to the umbilical cord insertions in monochorionic twin placentas.
INTRODUCTION
We aim to examine the location of the vascular equator according to the umbilical cord insertions in monochorionic twin placentas.
METHODS
We combined two prospective series of monochorionic diamniotic twin placentas of patients included in the first trimester between 2004 and 2008, and between 2016 and 2019. We injected the placentas after birth and divided them into three groups, with respectively concordant (eccentric-eccentric, marginal-marginal, and velamentous-velamentous), intermediate (eccentric-marginal and marginal-velamentous) and discordant (eccentric-velamentous) cord insertions. For each unidirectional anastomosis, we determined the cord-anastomosis ratio and then calculated the mean ratio per placenta in each group. We also calculated the deviation from the midline in all groups.
RESULTS
195 placentas were included. In concordant placentas, the mean cord-anastomosis ratio was 0.957 (95% CI [0.908-1.009]). In placentas with intermediate discordance, the mean ratio was 0.886 (95% CI [0.828-0.948]) and in discordant placentas it was 0.797 (95% CI [0,708-0.897]) (p < 0.001). In concordant placentas, the equator was in the middle of the cord insertions with an average deviation of 0.2 cm (95% CI [-0.1 - 0.3]). In the intermediate placentas, the equator deviated on average 0.5 cm (95% CI [0.2-0.8]) and was displaced from the middle towards the most central cord insertion. In discordant placentas, there was an average displacement of 1.0 cm (95% CI [0.50-1.6]).
DISCUSSION
In concordant placentas, the vascular equator lies in the middle between both cord insertions. In intermediate and discordant placentas, the equator is closer to the more central cord insertion.
Topics: Adult; Female; Fetofetal Transfusion; Humans; Laser Therapy; Placenta; Pregnancy; Twins, Monozygotic; Ultrasonography, Prenatal; Umbilical Cord
PubMed: 32988575
DOI: 10.1016/j.placenta.2020.05.008 -
Current Medical Research and Opinion Nov 2018Smoking during pregnancy is able to alter the structure and function of the placenta. In the present study, quantitative changes of the placenta in smoking mothers were...
OBJECTIVE
Smoking during pregnancy is able to alter the structure and function of the placenta. In the present study, quantitative changes of the placenta in smoking mothers were investigated compared to healthy controls by Cavalieri's point counting method.
METHODS
Twenty placentas from heavy smoking mothers and non-smoker controls (n = 10 in each group) were selected. Systematic uniform random sampling (SURS) was used for sample selection and tissue sectioning. Quantitative parameters of the placenta in the selected sections were estimated after Masson's trichrome staining. Differences between the two groups were determined by the Mann Whitney U test and the significance level was set at p < .05.
RESULTS
Results showed that there was a significant difference in the placental weight, total volume of placenta, intervillous space, fibrin and syncytiotrophoblast between the heavy smoker group and the control group (p < .05). The differences in the volume density of fibrin and blood vessels between the smoker and control groups were statistically significant (p < .05).
CONCLUSIONS
Our findings suggested that quantitative parameters of the placenta significantly changed in placentas from the smoker group compared to controls. These changes can probably be associated with pregnancy complications in smoking mothers and may affect the development and survival of the fetus and even its future life.
Topics: Adult; Correlation of Data; Female; Humans; Mothers; Placenta; Pregnancy; Pregnancy Complications; Severity of Illness Index; Smoking; Tobacco Use Disorder; Trophoblasts
PubMed: 29469634
DOI: 10.1080/03007995.2018.1444590 -
Magnetic Resonance in Medicine Aug 2018To assess which microstructural models best explain the diffusion-weighted MRI signal in the human placenta.
PURPOSE
To assess which microstructural models best explain the diffusion-weighted MRI signal in the human placenta.
METHODS
The placentas of nine healthy pregnant subjects were scanned with a multishell, multidirectional diffusion protocol at 3T. A range of multicompartment biophysical models were fit to the data, and ranked using the Bayesian information criterion.
RESULTS
Anisotropic extensions to the intravoxel incoherent motion model, which consider the effect of coherent orientation in both microvascular structure and tissue microstructure, consistently had the lowest Bayesian information criterion values. Model parameter maps and model selection results were consistent with the physiology of the placenta and surrounding tissue.
CONCLUSION
Anisotropic intravoxel incoherent motion models explain the placental diffusion signal better than apparent diffusion coefficient, intravoxel incoherent motion, and diffusion tensor models, in information theoretic terms, when using this protocol. Future work will aim to determine if model-derived parameters are sensitive to placental pathologies associated with disorders, such as fetal growth restriction and early-onset pre-eclampsia. Magn Reson Med 80:756-766, 2018. © 2017 The Authors Magnetic Resonance in Medicine published by Wiley Periodicals, Inc. on behalf of International Society for Magnetic Resonance in Medicine. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Topics: Anisotropy; Bayes Theorem; Diffusion Magnetic Resonance Imaging; Female; Humans; Image Processing, Computer-Assisted; Microcirculation; Placenta; Pregnancy
PubMed: 29230859
DOI: 10.1002/mrm.27036 -
Wiadomosci Lekarskie (Warsaw, Poland :... 2022The aim: The impact of undifferentiated connective tissue dysplasia on the formation of the placenta.
OBJECTIVE
The aim: The impact of undifferentiated connective tissue dysplasia on the formation of the placenta.
PATIENTS AND METHODS
Materials and methods: The morphostructure of 50 placentas with the undifferentiated connective tissue syndrome and 50 placentas of women with physiological pregnancy and absence of connective tissue pathology was studied.
RESULTS
Results: The results of morphological studies have shown that the main pathogenetic link of placental dysfunction with highly resistant blood flow in the umbilical arteries in pregnant women with undifferentiated connective tissue dysplasia syndrome is a disorder of functional differentiation of the villous tree.In these cases the dominats were large and medium-sized villi with narrowed lumen in arterial, venular and capillary vessels and arterial spasm and venous plethora, as well as with numerous chaotically sclerosed villi, indicating stage I and II of placental. There is a large amount of fibrins in intervillous space which narrows it and leads to violation of microcirculation and placenta tissue hypoxia.
CONCLUSION
Conclusions: The morphological basis of high flow resistance in the umbilical artery with the undifferentiated connective tissue dysplasia syndrome in pregnant women is a pathological immaturity of the placental villous tree. Morphological study of the architecture of the stem and intermediate placental villi revealed a violation of the structure of collagen fibers in the form of lack of crosslinks of bundles of collagen fibers.
Topics: Female; Pregnancy; Humans; Placenta; Chorionic Villi; Arteries; Collagen; Connective Tissue
PubMed: 36472281
DOI: 10.36740/WLek202210128 -
Placenta Feb 2021To explore the involvement of signal transducers and activators of transcription (STATs) in trophoblast differentiation.
INTRODUCTION
To explore the involvement of signal transducers and activators of transcription (STATs) in trophoblast differentiation.
METHODS AND RESULTS
First, the localization of STATs in human placentas was detected via immunohistochemistry (IHC) and immunofluorescence (IF). Cytotrophoblasts (CTBs) expressed both STAT1 and 3, but syncytiotrophoblasts (STBs) did not. Staining for these two proteins showed a distinct upregulation from the proximal part to the distal end of cell columns. STAT5B was mainly expressed in the STBs, low in the CTBs, and absent in the extravillous trophoblasts (EVTs). Next, the 44 placenta samples were tested via western blot (WB) and quantitative real time polymerase chain reaction (qRT-PCR). We found a decrease in STAT1 and 3 and an increase in STAT5B as gestation increased from five to 10 weeks. Then, an in vitro co-culture model of placenta with or without decidua stromal cells (DSCs), as detected via flow cytometry, revealed an increase in the human leukocyte antigen (HLA)-G positive rate in trophoblasts from placentas co-cultured with DSCs, accompanied by an increase in p-STAT1 and 3 and a decrease in p-STAT5 and STAT5B. Finally, mRNA of matrix metalloproteinases (MMPs) and integrins after STAT silencing in HTR-8/SVneo was detected via qRT-PCR. STAT1 silencing decreased MMP9 expression, STAT3 silencing decreased MMP9, integrin α6, and β4 expression, and STAT5B silencing increased MMP2 and integrin β1 expression.
DISCUSSION
Different trophoblasts showed distinct STAT expression profiles which were related to their MMP and integrin expression. DSCs promoted trophoblast differentiation into EVTs, possibly by regulating the STAT expression of the trophoblasts.
Topics: Adult; Cell Differentiation; Cell Line; Female; Humans; Matrix Metalloproteinases; Placenta; Pregnancy; STAT Transcription Factors; Stromal Cells; Trophoblasts; Young Adult
PubMed: 33556719
DOI: 10.1016/j.placenta.2021.01.021