Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 59.734
Filtrar
1.
Lancet Planet Health ; 8(5): e297-e308, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38723642

RESUMEN

BACKGROUND: Pregnancy air pollution exposure (PAPE) has been linked to a wide range of adverse birth and childhood outcomes, but there is a paucity of data on its influence on the placental epigenome, which can regulate the programming of physiological functions and affect child development. This study aimed to investigate the association between prenatal air pollutant exposure concentrations and changes in placental DNA methylation patterns, and to explore the potential windows of susceptibility and sex-specific alterations. METHODS: This multi-site study used three prospective population-based mother-child cohorts: EDEN, PELAGIE, and SEPAGES, originating from four French geographical regions (Nancy, Poitiers, Brittany, and Grenoble). Pregnant women were included between 2003 and 2006 for EDEN and PELAGIE, and between 2014 and 2017 for SEPAGES. The main eligibility criteria were: being older than 18 years, having a singleton pregnancy, and living and planning to deliver in one of the maternity clinics in one of the study areas. A total of 1539 mother-child pairs were analysed, measuring placental DNA methylation using Illumina BeadChips. We used validated spatiotemporally resolved models to estimate PM2·5, PM10, and NO2 exposure over each trimester of pregnancy at the maternal residential address. We conducted a pooled adjusted epigenome-wide association study to identify differentially methylated 5'-C-phosphate-G-3' (CpG) sites and regions (assessed using the Infinium HumanMethylationEPIC BeadChip array, n=871), including sex-specific and sex-linked alterations, and independently validated our results (assessed using the Infinium HumanMethylation450 BeadChip array, n=668). FINDINGS: We identified four CpGs and 28 regions associated with PAPE in the total population, 469 CpGs and 87 regions in male infants, and 150 CpGs and 66 regions in female infants. We validated 35% of the CpGs available. More than 30% of the identified CpGs were related to one (or more) birth outcome and most significant alterations were enriched for neural development, immunity, and metabolism related genes. The 28 regions identified for both sexes overlapped with imprinted genes (four genes), and were associated with neurodevelopment (nine genes), immune system (seven genes), and metabolism (five genes). Most associations were observed for the third trimester for female infants (134 of 150 CpGs), and throughout pregnancy (281 of 469 CpGs) and the first trimester (237 of 469 CpGs) for male infants. INTERPRETATION: These findings highlight the molecular pathways through which PAPE might affect child health in a widespread and sex-specific manner, identifying the genes involved in the major physiological functions of a developing child. Further studies are needed to elucidate whether these epigenetic changes persist and affect health later in life. FUNDING: French Agency for National Research, Fondation pour la Recherche Médicale, Fondation de France, and the Plan Cancer.


Asunto(s)
Contaminantes Atmosféricos , Contaminación del Aire , Metilación de ADN , Exposición Materna , Placenta , Humanos , Femenino , Embarazo , Placenta/efectos de los fármacos , Placenta/metabolismo , Estudios Prospectivos , Exposición Materna/efectos adversos , Adulto , Contaminación del Aire/efectos adversos , Masculino , Contaminantes Atmosféricos/efectos adversos , Contaminantes Atmosféricos/análisis , Francia , Efectos Tardíos de la Exposición Prenatal/genética , Resultado del Embarazo , Recién Nacido , Adulto Joven
2.
BMJ Case Rep ; 17(5)2024 May 09.
Artículo en Inglés | MEDLINE | ID: mdl-38724211

RESUMEN

Placental mesenchymal dysplasia (PMD) is an exceptionally rare placental anomaly characterised by placentomegaly and grape-like vesicles resembling partial mole on ultrasonography, yet it can coexist with a viable fetus. We present the case of a primigravida who presented at 22 weeks gestation with a suspected partial mole but with a normally growing fetus. The differential diagnoses considered included placental mesenchymal disease, partial mole and twin pregnancy with molar pregnancy. With normal beta HCG levels and prenatal invasive testing reports, a probable diagnosis of PMD was made, and after thorough counselling, the decision was made to continue the pregnancy. The pregnancy progressed until 37 weeks, culminating in the uneventful delivery of a 2.4 kg healthy male infant. Histopathology confirmed PMD. Early recognition and management of PMD pose significant challenges, given its rarity. Prenatal identification of PMD during both early and late gestation could avert unnecessary termination of pregnancy.


Asunto(s)
Mola Hidatiforme , Enfermedades Placentarias , Placenta , Humanos , Embarazo , Femenino , Mola Hidatiforme/diagnóstico , Mola Hidatiforme/diagnóstico por imagen , Diagnóstico Diferencial , Enfermedades Placentarias/diagnóstico , Enfermedades Placentarias/diagnóstico por imagen , Placenta/patología , Placenta/diagnóstico por imagen , Adulto , Masculino , Recién Nacido , Ultrasonografía Prenatal , Resultado del Embarazo
3.
Int J Mol Sci ; 25(9)2024 Apr 23.
Artículo en Inglés | MEDLINE | ID: mdl-38731805

RESUMEN

We are pleased to present this Special Issue of the International Journal of Molecular Sciences, entitled "Physiology and Pathophysiology of Placenta 2 [...].


Asunto(s)
Placenta , Humanos , Placenta/fisiopatología , Placenta/metabolismo , Placenta/patología , Embarazo , Femenino , Animales , Enfermedades Placentarias/fisiopatología , Enfermedades Placentarias/patología
4.
Int J Mol Sci ; 25(9)2024 Apr 27.
Artículo en Inglés | MEDLINE | ID: mdl-38731997

RESUMEN

Glucose, the primary energy substrate for fetal oxidative processes and growth, is transferred from maternal to fetal circulation down a concentration gradient by placental facilitative glucose transporters. In sheep, SLC2A1 and SLC2A3 are the primary transporters available in the placental epithelium, with SLC2A3 located on the maternal-facing apical trophoblast membrane and SLC2A1 located on the fetal-facing basolateral trophoblast membrane. We have previously reported that impaired placental SLC2A3 glucose transport resulted in smaller, hypoglycemic fetuses with reduced umbilical artery insulin and glucagon concentrations, in addition to diminished pancreas weights. These findings led us to subject RNA derived from SLC2A3-RNAi (RNA interference) and NTS-RNAi (non-targeting sequence) fetal pancreases to qPCR followed by transcriptomic analysis. We identified a total of 771 differentially expressed genes (DEGs). Upregulated pathways were associated with fat digestion and absorption, particularly fatty acid transport, lipid metabolism, and cholesterol biosynthesis, suggesting a potential switch in energetic substrates due to hypoglycemia. Pathways related to molecular transport and cell signaling in addition to pathways influencing growth and metabolism of the developing pancreas were also impacted. A few genes directly related to gluconeogenesis were also differentially expressed. Our results suggest that fetal hypoglycemia during the first half of gestation impacts fetal pancreas development and function that is not limited to ß cell activity.


Asunto(s)
Hipoglucemia , Páncreas , Placenta , Interferencia de ARN , Transcriptoma , Embarazo , Animales , Femenino , Placenta/metabolismo , Ovinos , Páncreas/metabolismo , Páncreas/embriología , Hipoglucemia/genética , Hipoglucemia/metabolismo , Transportador de Glucosa de Tipo 3/genética , Transportador de Glucosa de Tipo 3/metabolismo , Feto/metabolismo , Desarrollo Fetal/genética , Regulación del Desarrollo de la Expresión Génica , Glucosa/metabolismo , Perfilación de la Expresión Génica
5.
Mol Biol Rep ; 51(1): 652, 2024 May 11.
Artículo en Inglés | MEDLINE | ID: mdl-38734792

RESUMEN

OBJECTIVE: To compare the mRNA expression of placental iron transporters (TfR-1 and FPN), markers of placental vascularization (VEGF and sFLT1) and marker of structural integrity (LMN-A) in term women with and without iron deficiency anemia. MATERIALS AND METHODS: A total of 30 pregnant women were enrolled; 15 cases of iron deficiency anemia (Hb 7-10.9 gm/dL) and 15 gestational age matched healthy controls (Hb ≥ 11 gm/dL). Peripheral venous blood was collected for assessment of hemoglobin levels and serum iron profile. Placental tissue was used for assessing the mRNA expression of TfR-1, FPN, VEGF, sFLT-1 and LMN-A via real time PCR. RESULTS: Placental expression of TfR-1, VEGF and LMN-A was increased in pregnant women with anemia compared to healthy pregnant controls. Placental expression of sFLT-1 was decreased in pregnant women with anemia compared to healthy pregnant controls. There was no change in the placental expression of FPN. CONCLUSION: The increased expression of TfR-1, VEGF and LMN-A in cases of iron deficiency anemia are most likely to be compensatory in nature to help maintain adequate fetal iron delivery. WHAT DOES THIS STUDY ADDS TO THE CLINICAL WORK: Compensatory changes in the placenta aimed at buffering transport of iron to the fetus are seen in pregnant women with anemia compared to healthy pregnant controls.


Asunto(s)
Anemia Ferropénica , Biomarcadores , Proteínas de Transporte de Catión , Hierro , Placenta , Receptores de Transferrina , Factor A de Crecimiento Endotelial Vascular , Humanos , Femenino , Embarazo , Placenta/metabolismo , Adulto , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Anemia Ferropénica/genética , Anemia Ferropénica/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Factor A de Crecimiento Endotelial Vascular/metabolismo , Proteínas de Transporte de Catión/genética , Proteínas de Transporte de Catión/metabolismo , Hierro/metabolismo , Biomarcadores/metabolismo , Biomarcadores/sangre , Receptor 1 de Factores de Crecimiento Endotelial Vascular/genética , Receptor 1 de Factores de Crecimiento Endotelial Vascular/metabolismo , Estudios de Casos y Controles , Antígenos CD/metabolismo , Antígenos CD/genética , ARN Mensajero/genética , ARN Mensajero/metabolismo , Expresión Génica/genética
6.
Clin Perinatol ; 51(2): 425-439, 2024 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-38705650

RESUMEN

This review illuminates the complex interplay between various maternal microbiomes and their influence on preterm birth (PTB), a driving and persistent contributor to neonatal morbidity and mortality. Here, we examine the dynamics of oral, gastrointestinal (gut), placental, and vaginal microbiomes, dissecting their roles in the pathogenesis of PTB. Importantly, focusing on the vaginal microbiome and PTB, the review highlights (1) a protective role of Lactobacillus species; (2) an increased risk with select anaerobes; and (3) the influence of social health determinants on the composition of vaginal microbial communities.


Asunto(s)
Microbioma Gastrointestinal , Microbiota , Placenta , Nacimiento Prematuro , Vagina , Humanos , Femenino , Embarazo , Nacimiento Prematuro/microbiología , Nacimiento Prematuro/epidemiología , Vagina/microbiología , Recién Nacido , Placenta/microbiología , Microbioma Gastrointestinal/fisiología , Lactobacillus , Boca/microbiología
7.
Eur J Med Res ; 29(1): 285, 2024 May 14.
Artículo en Inglés | MEDLINE | ID: mdl-38745325

RESUMEN

INTRODUCTION: Hydrogen (H2) is regarded as a novel therapeutic agent against several diseases owing to its inherent biosafety. Bronchopulmonary dysplasia (BPD) has been widely considered among adverse pregnancy outcomes, without effective treatment. Placenta plays a role in defense, synthesis, and immunity, which provides a new perspective for the treatment of BPD. This study aimed to investigate if H2 reduced the placental inflammation to protect the neonatal rat against BPD damage and potential mechanisms. METHODS: We induced neonatal BPD model by injecting lipopolysaccharide (LPS, 1 µg) into the amniotic fluid at embryonic day 16.5 as LPS group. LPS + H2 group inhaled 42% H2 gas (4 h/day) until the samples were collected. We primarily analyzed the neonatal outcomes and then compared inflammatory levels from the control group (CON), LPS group and LPS + H2 group. HE staining was performed to evaluate inflammatory levels. RNA sequencing revealed dominant differentially expressed genes. Bioinformatics analysis (GO and KEGG) of RNA-seq was applied to mine the signaling pathways involved in protective effect of H2 on the development of LPS-induced BPD. We further used qRT-PCR, Western blot and ELISA methods to verify differential expression of mRNA and proteins. Moreover, we verified the correlation between the upstream signaling pathways and the downstream targets in LPS-induced BPD model. RESULTS: Upon administration of H2, the inflammatory infiltration degree of the LPS-induced placenta was reduced, and infiltration significantly narrowed. Hydrogen normalized LPS-induced perturbed lung development and reduced the death ratio of the fetus and neonate. RNA-seq results revealed the importance of inflammatory response biological processes and Toll-like receptor signaling pathway in protective effect of hydrogen on BPD. The over-activated upstream signals [Toll-like receptor 4 (TLR4), nuclear factor kappa-B p65 (NF-κB p65), Caspase1 (Casp1) and NLR family pyrin domain containing 3 (NLRP3) inflammasome] in LPS placenta were attenuated by H2 inhalation. The downstream targets, inflammatory cytokines/chemokines [interleukin (IL)-6, IL-18, IL-1ß, C-C motif chemokine ligand 2 (CCL2) and C-X-C motif chemokine ligand 1 (CXCL1)], were decreased both in mRNA and protein levels by H2 inhalation in LPS-induced placentas to rescue them from BPD. Correlation analysis displayed a positive association of TLR4-mediated signaling pathway both proinflammatory cytokines and chemokines in placenta. CONCLUSION: H2 inhalation ameliorates LPS-induced BPD by inhibiting excessive inflammatory cytokines and chemokines via the TLR4-NFκB-IL6/NLRP3 signaling pathway in placenta and may be a potential therapeutic strategy for BPD.


Asunto(s)
Displasia Broncopulmonar , Hidrógeno , Inflamación , Lipopolisacáridos , FN-kappa B , Proteína con Dominio Pirina 3 de la Familia NLR , Placenta , Transducción de Señal , Receptor Toll-Like 4 , Femenino , Embarazo , Lipopolisacáridos/toxicidad , Hidrógeno/farmacología , Hidrógeno/uso terapéutico , Animales , Placenta/metabolismo , Placenta/efectos de los fármacos , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética , Transducción de Señal/efectos de los fármacos , Ratas , Proteína con Dominio Pirina 3 de la Familia NLR/metabolismo , Proteína con Dominio Pirina 3 de la Familia NLR/genética , FN-kappa B/metabolismo , Inflamación/metabolismo , Inflamación/tratamiento farmacológico , Administración por Inhalación , Displasia Broncopulmonar/metabolismo , Displasia Broncopulmonar/inducido químicamente , Displasia Broncopulmonar/tratamiento farmacológico , Displasia Broncopulmonar/prevención & control , Interleucina-6/metabolismo , Interleucina-6/genética , Ratas Sprague-Dawley , Modelos Animales de Enfermedad
8.
J Biomed Mater Res B Appl Biomater ; 112(5): e35414, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38733611

RESUMEN

Utilizing natural scaffold production derived from extracellular matrix components presents a promising strategy for advancing in vitro spermatogenesis. In this study, we employed decellularized human placental tissue as a scaffold, upon which neonatal mouse spermatogonial cells (SCs) were cultured three-dimensional (3D) configuration. To assess cellular proliferation, we examined the expression of key markers (Id4 and Gfrα1) at both 1 and 14 days into the culture. Our quantitative reverse transcription-polymerase chain reaction (qRT-PCR) analysis revealed a notable increase in Gfrα1 gene expression, with the 3D culture group exhibiting the highest levels. Furthermore, the relative frequency of Gfrα1-positive cells significantly rose from 38.1% in isolated SCs to 46.13% and 76.93% in the two-dimensional (2D) and 3D culture systems, respectively. Moving forward to days 14 and 35 of the culture period, we evaluated the expression of differentiating markers (Sycp3, acrosin, and Protamine 1). Sycp3 and Prm1 gene expression levels were upregulated in both 2D and 3D cultures, with the 3D group displaying the highest expression. Additionally, acrosin gene expression increased notably within the 3D culture. Notably, at the 35-day mark, the percentage of Prm1-positive cells in the 3D group (36.4%) significantly surpassed that in the 2D group (10.96%). This study suggests that the utilization of placental scaffolds holds significant promise as a bio-scaffold for enhancing mouse in vitro spermatogenesis.


Asunto(s)
Diferenciación Celular , Proliferación Celular , Placenta , Animales , Femenino , Ratones , Masculino , Humanos , Placenta/citología , Placenta/metabolismo , Embarazo , Espermatogonias/citología , Espermatogonias/metabolismo , Andamios del Tejido/química , Matriz Extracelular Descelularizada/química , Matriz Extracelular Descelularizada/metabolismo , Células Madre/metabolismo , Células Madre/citología
9.
Malar J ; 23(1): 130, 2024 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-38693572

RESUMEN

BACKGROUND: The sequestration of Plasmodium falciparum infected erythrocytes in the placenta, and the resulting inflammatory response affects maternal and child health. Despite existing information, little is known about the direct impact of P. falciparum on the placental barrier formed by trophoblast and villous stroma. This study aimed to assess placental tissue damage caused by P. falciparum in human placental explants (HPEs). METHODS: HPEs from chorionic villi obtained of human term placentas (n = 9) from normal pregnancies were exposed to P. falciparum-infected erythrocytes (IE) for 24 h. HPEs were embedded in paraffin blocks and used to study tissue damage through histopathological and histochemical analysis and apoptosis using TUNEL staining. Culture supernatants were collected to measure cytokine and angiogenic factors and to determine LDH activity as a marker of cytotoxicity. A subset of archived human term placenta paraffin-embedded blocks from pregnant women with malaria were used to confirm ex vivo findings. RESULTS: Plasmodium falciparum-IE significantly damages the trophoblast layer and the villous stroma of the chorionic villi. The increased LDH activity and pathological findings such as syncytial knots, fibrin deposits, infarction, trophoblast detachment, and collagen disorganization supported these findings. The specific damage to the trophoblast and the thickening of the subjacent basal lamina were more pronounced in the ex vivo infection. In contrast, apoptosis was higher in the in vivo infection. This disparity could be attributed to the duration of exposure to the infection, which significantly varied between individuals naturally exposed over time and the 24-h exposure in the ex vivo HPE model. CONCLUSION: Exposure to P. falciparum-IE induces a detachment of the syncytiotrophoblast, disorganization of the stroma villi, and an increase in apoptosis, alterations that may be associated with adverse results such as intrauterine growth restriction and low birth weight.


Asunto(s)
Vellosidades Coriónicas , Plasmodium falciparum , Trofoblastos , Humanos , Femenino , Vellosidades Coriónicas/parasitología , Vellosidades Coriónicas/patología , Embarazo , Plasmodium falciparum/fisiología , Trofoblastos/parasitología , Apoptosis , Malaria Falciparum/parasitología , Malaria Falciparum/patología , Placenta/parasitología , Placenta/patología , Citocinas/metabolismo
10.
Front Immunol ; 15: 1380629, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38745664

RESUMEN

Introduction: Postpartum preeclampsia (PPPE) is an under-diagnosed condition, developing within 48 hours to 6 weeks following an uncomplicated pregnancy. The etiology of PPPE is still unknown, leaving patients vulnerable and making the identification and treatment of patients requiring postpartum care an unmet need. We aimed to understand the immune contribution to PPPE at the time of diagnosis, as well as uncover the predictive potential of perinatal biomarkers for the early postnatal identification of high-risk patients. Methods: Placentas were collected at delivery from uncomplicated pregnancies (CTL) and PPPE patients for immunohistochemistry analysis. In this initial study, blood samples in PPPE patients were collected at the time of PPPE diagnosis (48h-25 days postpartum; mean 7.4 days) and compared to CTL blood samples taken 24h after delivery. Single-cell transcriptomics, flow cytometry, intracellular cytokine staining, and the circulating levels of inflammatory mediators were evaluated in the blood. Results: Placental CD163+ cells and 1st trimester blood pressures can be valuable non-invasive and predictive biomarkers of PPPE with strong clinical application prospects. Furthermore, changes in immune cell populations, as well as cytokine production by CD14+, CD4+, and CD8+ cells, suggested a dampened response with an exhausted phenotype including decreased IL1ß, IL12, and IFNγ as well as elevated IL10. Discussion: Understanding maternal immune changes at the time of diagnosis and prenatally within the placenta in our sizable cohort will serve as groundwork for pre-clinical and clinical research, as well as guiding clinical practice for example in the development of immune-targeted therapies, and early postnatal identification of patients who would benefit from more thorough follow-ups and risk education in the weeks following an uncomplicated pregnancy.


Asunto(s)
Biomarcadores , Placenta , Periodo Posparto , Preeclampsia , Femenino , Humanos , Embarazo , Preeclampsia/inmunología , Preeclampsia/diagnóstico , Preeclampsia/sangre , Biomarcadores/sangre , Adulto , Placenta/inmunología , Placenta/metabolismo , Periodo Posparto/inmunología , Citocinas/sangre , Citocinas/metabolismo , Antígenos CD , Receptores de Superficie Celular/metabolismo
11.
J Pregnancy ; 2024: 6620156, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38745869

RESUMEN

Background: The cannabinoid receptor (CBR) plays a significant role in oogenesis, pregnancy, and childbirth. It might also play a significant role in preterm birth (PTB). The aim of the study was to investigate the association between the expression of the CBR in the placenta and the incidence of PTB. Methods: This prospective, observational, multicentre preliminary study was conducted on placental samples obtained from 109 women. The study included 95 patients hospitalized due to the high risk of PTB. They were divided into two groups: Group 1, where the expression of the CBR1 and CBR1a was analyzed, and Group 2, in which we examined CBR2 expression. The control group, that is, Group 3, consisted of 14 women who delivered at term, and their placentas were tested for the presence of all three receptor types (CBR1, CBR1a, and CBR2). Results: The study used reverse transcription and real-time PCR methods to assess the expression of CBRs in the placental tissues. The expression of the CBR2, CBR1, and CBR1a receptors was significantly lower in the placentas of women after PTB compared to those after term births, p = 0.038, 0.033, and 0.034, respectively. Conclusions: The presence of CBR mRNA in the human placental tissue was confirmed. The decreased expression of CBRs could serve as an indicator in predicting PTB.


Asunto(s)
Placenta , Nacimiento Prematuro , Receptor Cannabinoide CB1 , Receptor Cannabinoide CB2 , Humanos , Femenino , Embarazo , Placenta/metabolismo , Nacimiento Prematuro/metabolismo , Estudios Prospectivos , Adulto , Receptor Cannabinoide CB2/metabolismo , Receptor Cannabinoide CB2/genética , Receptor Cannabinoide CB1/metabolismo , Receptor Cannabinoide CB1/genética , Estudios de Casos y Controles , ARN Mensajero/metabolismo , Receptores de Cannabinoides/metabolismo , Receptores de Cannabinoides/genética
12.
Mediators Inflamm ; 2024: 9986187, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38716374

RESUMEN

Objective: Fetal growth restriction (FGR) is a significant contributor to negative pregnancy and postnatal developmental outcomes. Currently, the exact pathological mechanism of FGR remains unknown. This study aims to utilize multiomics sequencing technology to investigate potential relationships among mRNA, gut microbiota, and metabolism in order to establish a theoretical foundation for diagnosing and understanding the molecular mechanisms underlying FGR. Methods: In this study, 11 healthy pregnant women and nine pregnant women with FGR were divided into Control group and FGR group based on the health status. Umbilical cord blood, maternal serum, feces, and placental tissue samples were collected during delivery. RNA sequencing, 16S rRNA sequencing, and metabolomics methods were applied to analyze changes in umbilical cord blood circulating mRNA, fecal microbiota, and metabolites. RT-qPCR, ELISA, or western blot were used to detect the expression of top 5 differential circulating mRNA in neonatal cord blood, maternal serum, or placental tissue samples. Correlation between differential circulating mRNA, microbiota, and metabolites was analyzed by the Spearman coefficient. Results: The top 5 mRNA genes in FGR were altered with the downregulation of TRIM34, DEFA3, DEFA1B, DEFA1, and QPC, and the upregulation of CHPT1, SMOX, FAM83A, GDF15, and NAPG in newborn umbilical cord blood, maternal serum, and placental tissue. The abundance of Bacteroides, Akkermansia, Eubacterium_coprostanoligenes_group, Phascolarctobacterium, Parasutterella, Odoribacter, Lachnospiraceae_UCG_010, and Dielma were significantly enriched in the FGR group. Metabolites such as aspartic acid, methionine, alanine, L-tryptophan, 3-methyl-2-oxovalerate, and ketoleucine showed notable functional alterations. Spearman correlation analysis indicated that metabolites like methionine and alanine, microbiota (Tyzzerella), and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) might play a role as mediators in the communication between the gut and circulatory system interaction in FGR. Conclusion: Metabolites (METHIONINE, alanine) as well as microbiota (Tyzzerella) and circulating mRNA (TRIM34, SMOX, FAM83A, NAPG) were possible mediators that communicated the interaction between the gut and circulatory systems in FGR.


Asunto(s)
Retardo del Crecimiento Fetal , Microbioma Gastrointestinal , ARN Mensajero , Humanos , Femenino , Retardo del Crecimiento Fetal/metabolismo , Retardo del Crecimiento Fetal/microbiología , Embarazo , ARN Mensajero/metabolismo , Adulto , Sangre Fetal/metabolismo , ARN Ribosómico 16S/genética , Placenta/metabolismo , Placenta/microbiología , Heces/microbiología , Recién Nacido , Multiómica
13.
Front Immunol ; 15: 1385762, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38707901

RESUMEN

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.


Asunto(s)
Placenta , Humanos , Embarazo , Femenino , Placenta/inmunología , Placenta/metabolismo , Animales , Placentación , Endometrio/inmunología , Endometrio/metabolismo , Neoplasias/inmunología , Neoplasias/etiología , Implantación del Embrión/inmunología
14.
Ter Arkh ; 96(3): 266-272, 2024 Apr 16.
Artículo en Ruso | MEDLINE | ID: mdl-38713042

RESUMEN

AIM: To investigate the antitumor effects of human placenta hydrolysate (HPH) peptides on three hormone-dependent human cell lines: prostate adenocarcinoma, breast carcinoma, and ovarian cancer by metabolic analysis of cell cultures. MATERIALS AND METHODS: The effect of HPH on tumor and control tumor cell lines was evaluated. Study stages: (A) de novo peptide sequencing by collision-induced dissociation mass spectrometry; (B) detection of peptides with anti-tumor properties; (C) expert analysis of the obtained lists of peptides. RESULTS: Dose-dependent cytotoxic effects of HPH on three tumor cell lines are shown: PC-3 (human prostate adenocarcinomas), OAW-42 (human ovarian cancer), BT-474 (human breast carcinomas), and IC50 constants (1.3-2.8 mg/ml) were obtained. The analysis of the HPH peptide fraction showed more than 70 peptides with antitumor properties in the composition of this HPH, including kinase inhibitors: mitogen-activated protein kinases, kappa-bi nuclear factor inhibitor kinase, AKT serine/threonine kinase 1, protein kinase C zeta, interleukin-1 receptor-associated kinase 4 and cyclin-dependent kinase 1. CONCLUSION: The results of the study indicate not only the oncological safety of the HPH used in therapy but also the mild antitumor effects of this HPH at high concentrations.


Asunto(s)
Neoplasias de la Mama , Placenta , Neoplasias de la Próstata , Humanos , Femenino , Placenta/metabolismo , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/patología , Embarazo , Neoplasias de la Próstata/tratamiento farmacológico , Masculino , Línea Celular Tumoral , Antineoplásicos/farmacología , Neoplasias Ováricas/tratamiento farmacológico , Células PC-3 , Hidrolisados de Proteína/farmacología , Relación Dosis-Respuesta a Droga
15.
J Neuroinflammation ; 21(1): 118, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715090

RESUMEN

Maternal inflammation during gestation is associated with a later diagnosis of neurodevelopmental disorders including autism spectrum disorder (ASD). However, the specific impact of maternal immune activation (MIA) on placental and fetal brain development remains insufficiently understood. This study aimed to investigate the effects of MIA by analyzing placental and brain tissues obtained from the offspring of pregnant C57BL/6 dams exposed to polyinosinic: polycytidylic acid (poly I: C) on embryonic day 12.5. Cytokine and mRNA content in the placenta and brain tissues were assessed using multiplex cytokine assays and bulk-RNA sequencing on embryonic day 17.5. In the placenta, male MIA offspring exhibited higher levels of GM-CSF, IL-6, TNFα, and LT-α, but there were no differences in female MIA offspring. Furthermore, differentially expressed genes (DEG) in the placental tissues of MIA offspring were found to be enriched in processes related to synaptic vesicles and neuronal development. Placental mRNA from male and female MIA offspring were both enriched in synaptic and neuronal development terms, whereas females were also enriched for terms related to excitatory and inhibitory signaling. In the fetal brain of MIA offspring, increased levels of IL-28B and IL-25 were observed with male MIA offspring and increased levels of LT-α were observed in the female offspring. Notably, we identified few stable MIA fetal brain DEG, with no male specific difference whereas females had DEG related to immune cytokine signaling. Overall, these findings support the hypothesis that MIA contributes to the sex- specific abnormalities observed in ASD, possibly through altered neuron developed from exposure to inflammatory cytokines. Future research should aim to investigate how interactions between the placenta and fetal brain contribute to altered neuronal development in the context of MIA.


Asunto(s)
Encéfalo , Citocinas , Ratones Endogámicos C57BL , Trastornos del Neurodesarrollo , Placenta , Efectos Tardíos de la Exposición Prenatal , Caracteres Sexuales , Femenino , Animales , Embarazo , Masculino , Citocinas/metabolismo , Citocinas/genética , Ratones , Encéfalo/metabolismo , Encéfalo/inmunología , Encéfalo/embriología , Placenta/metabolismo , Placenta/inmunología , Efectos Tardíos de la Exposición Prenatal/inmunología , Efectos Tardíos de la Exposición Prenatal/metabolismo , Efectos Tardíos de la Exposición Prenatal/inducido químicamente , Trastornos del Neurodesarrollo/genética , Trastornos del Neurodesarrollo/inmunología , Trastornos del Neurodesarrollo/metabolismo , Poli I-C/toxicidad , Transcriptoma , Modelos Animales de Enfermedad , Feto/metabolismo
16.
Genome Biol ; 25(1): 117, 2024 May 07.
Artículo en Inglés | MEDLINE | ID: mdl-38715110

RESUMEN

BACKGROUND: Preeclampsia, one of the most lethal pregnancy-related diseases, is associated with the disruption of uterine spiral artery remodeling during placentation. However, the early molecular events leading to preeclampsia remain unknown. RESULTS: By analyzing placentas from preeclampsia, non-preeclampsia, and twin pregnancies with selective intrauterine growth restriction, we show that the pathogenesis of preeclampsia is attributed to immature trophoblast and maldeveloped endothelial cells. Delayed epigenetic reprogramming during early extraembryonic tissue development leads to generation of excessive immature trophoblast cells. We find reduction of de novo DNA methylation in these trophoblast cells results in selective overexpression of maternally imprinted genes, including the endoretrovirus-derived gene PEG10 (paternally expressed gene 10). PEG10 forms virus-like particles, which are transferred from the trophoblast to the closely proximate endothelial cells. In normal pregnancy, only a low amount of PEG10 is transferred to maternal cells; however, in preeclampsia, excessive PEG10 disrupts maternal vascular development by inhibiting TGF-beta signaling. CONCLUSIONS: Our study reveals the intricate epigenetic mechanisms that regulate trans-generational genetic conflict and ultimately ensure proper maternal-fetal interface formation.


Asunto(s)
Preeclampsia , Trofoblastos , Remodelación Vascular , Preeclampsia/genética , Embarazo , Femenino , Humanos , Trofoblastos/metabolismo , Remodelación Vascular/genética , Placenta/metabolismo , Metilación de ADN , Epigénesis Genética , Células Endoteliales/metabolismo , Proteínas de Unión al ADN/genética , Proteínas de Unión al ADN/metabolismo , Impresión Genómica , Factor de Crecimiento Transformador beta/metabolismo , Retardo del Crecimiento Fetal/genética , Placentación/genética , Proteínas de Unión al ARN , Proteínas Reguladoras de la Apoptosis
17.
PLoS One ; 19(5): e0303471, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38718074

RESUMEN

OBJECTIVE: Preeclampsia (PE) is a severe complication of unclear pathogenesis associated with pregnancy. This research aimed to elucidate the properties of immune cell infiltration and potential biomarkers of PE based on bioinformatics analysis. MATERIALS AND METHODS: Two PE datasets were imported from the Gene ExpressioOmnibus (GEO) and screened to identify differentially expressed genes (DEGs). Significant module genes were identified by weighted gene co-expression network analysis (WGCNA). DEGs that interacted with key module genes (GLu-DEGs) were analyzed further by Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) analyses. The diagnostic value of the genes was assessed using receiver operating characteristic (ROC) curves and protein-protein interaction (PPI) networks were constructed using GeneMANIA, and GSVA analysis was performed using the MSigDB database. Immune cell infiltration was analyzed using the TISIDB database, and StarBase and Cytoscape were used to construct an RBP-mRNA network. The identified hub genes were validated in two independent datasets. For further confirmation, placental tissue from healthy pregnant women and women with PE were collected and analyzed using both RT-qPCR and immunohistochemistry. RESULTS: A total of seven GLu-DEGs were obtained and were found to be involved in pathways associated with the transport of sulfur compounds, PPAR signaling, and energy metabolism, shown by GO and KEGG analyses. GSVA indicated significant increases in adipocytokine signaling. Furthermore, single-sample Gene Set Enrichment Analysis (ssGSEA) indicated that the levels of activated B cells and T follicular helper cells were significantly increased in the PE group and were negatively correlated with GLu-DEGs, suggesting their potential importance. CONCLUSION: In summary, the results showed a correlation between glutamine metabolism and immune cells, providing new insights into the understandingPE pathogenesis and furnishing evidence for future advances in the treatment of this disease.


Asunto(s)
Redes Reguladoras de Genes , Glutamina , Preeclampsia , Mapas de Interacción de Proteínas , Humanos , Preeclampsia/genética , Preeclampsia/inmunología , Femenino , Embarazo , Mapas de Interacción de Proteínas/genética , Glutamina/metabolismo , Biología Computacional/métodos , Ontología de Genes , Perfilación de la Expresión Génica , Adulto , Placenta/metabolismo , Placenta/inmunología
18.
Am J Reprod Immunol ; 91(5): e13857, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38716824

RESUMEN

Preeclampsia, poses significant risks to both maternal and fetal well-being. Exosomes released by the placenta play a crucial role in intercellular communication and are recognized as potential carriers of essential information for placental development. These exosomes transport a payload of proteins, nucleic acids, and lipids that mirror the placental microenvironment. This review delves into the functional roles of placental exosomes and its contents shedding light on their involvement in vascular regulation and immune modulation in normal pregnancy. Discernible changes are reported in the composition and quantity of placental exosome contents in pregnancies affected by preeclampsia. The exosomes from preeclamptic mothers affect vascularization and fetal kidney development. The discussion also explores the implications of utilizing placental exosomes as biomarkers and the prospects of translating these findings into clinical applications. In conclusion, placental exosomes hold promise as a valuable avenue for deciphering the complexities of preeclampsia, providing crucial diagnostic and prognostic insights. As the field progresses, a more profound comprehension of the distinct molecular signatures carried by placental exosomes may open doors to innovative strategies for managing and offering personalized care to pregnancies affected by preeclampsia.


Asunto(s)
Exosomas , Placenta , Preeclampsia , Humanos , Embarazo , Preeclampsia/metabolismo , Exosomas/metabolismo , Femenino , Placenta/metabolismo , Placenta/inmunología , Biomarcadores/metabolismo , Animales , Comunicación Celular
19.
Ceska Gynekol ; 89(2): 151-155, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38704229

RESUMEN

The human placenta serves as a vital barrier between the mother and the developing fetus during pregnancy. A defect in the early development of the placenta is associated with severe pregnancy disorders. Despite its complex development, various molecular processes control placental development, and the specialization of trophoblast cells is still not fully understood. One primary obstacle is the lack of suitable cell model systems. Traditional two-dimensional (2D) cell cultures fail to mimic in vivo conditions and do not capture the intricate intercellular interactions vital for studying placental development. However, three-dimensional (3D) organoid models derived from stem cells that replicate natural cell organization and architecture have greatly improved our understanding of trophoblast behavior and its medicinal applications. Organoids with relevant phenotypes provide a valuable platform to model both placental physiology and pathology, including the modeling of placental disorders. They hold great promise for personalized medicine, improved diagnostics, and the evaluation of pharmaceutical drug efficacy and safety. This article provides a concise overview of trophoblast stem cells, trophoblast invasion, and the evolving role of organoids in gynecology.


Asunto(s)
Organoides , Células Madre , Trofoblastos , Humanos , Trofoblastos/fisiología , Organoides/fisiología , Femenino , Embarazo , Células Madre/fisiología , Placenta/citología , Placenta/fisiología , Placenta/patología , Placentación/fisiología
20.
Front Endocrinol (Lausanne) ; 15: 1371220, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38737551

RESUMEN

Background and objective: Aberrant epigenetic regulation and increased oxidative stress in the placenta play a significant role in placental pathophysiology and fetal programming in preeclampsia, a hypertensive disorder in human pregnancy. The purpose of the study is to investigate if hypermethylation of histone H3K9 occurs in placental trophoblasts from preeclampsia. Methods: Trophoblasts were isolated and cultured from 14 placentas, 7 from normotensive pregnant women and 7 from preeclamptic pregnancies. Methylated H3K9 expression and antioxidant superoxide dismutase expression were determined by Western blot. We also examined consequences of oxidative stress and the downstream effects of histone methyltransferase inhibition on H3K9 expression associated with antioxidant CuZn-SOD and Mn-SOD expression in placental trophoblasts. Results: We found that expression of mono-, di-, and tri-methylation of histone H3 lysine 9 (H3K9me1, H3K9me2 and H3K9me3) was significantly increased, p<0.01, which correlated with downregulation of antioxidant superoxide dismutase CuZn-SOD and Mn-SOD expression, in trophoblasts from preeclamptic placentas compared to those from uncomplicated control placentas. We further demonstrated hypoxia could promote histone H3K9 methylation in placental trophoblasts, and hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression was reversible when hypoxic condition was removed. In addition, we also uncovered that inhibition of methyltransferase not only prevented hypoxia-induced upregulation of H3K9me1, H3K9me2 and H3K9me3 expression, but also abolished hypoxia-induced downregulation of CuZn-SOD and Mn-SOD expression in placental trophoblasts. Conclusions: These findings are noteworthy and provide further evidence that increased oxidative stress in the intrauterine environment is likely a mechanism to induce aberrant histone modification in placental trophoblasts in preeclampsia. Moreover, CuZn-SOD and Mn-SOD expression/activity are possibly H3K9 methylation-dependent in placental trophoblasts, which further suggest that oxidative stress and aberrant histone modification have significant impact on placental trophoblasts/fetal programming in preeclampsia.


Asunto(s)
Histonas , Estrés Oxidativo , Placenta , Preeclampsia , Trofoblastos , Humanos , Femenino , Preeclampsia/metabolismo , Preeclampsia/genética , Preeclampsia/patología , Embarazo , Trofoblastos/metabolismo , Histonas/metabolismo , Adulto , Placenta/metabolismo , Metilación , Superóxido Dismutasa/metabolismo , Superóxido Dismutasa/genética , Metilación de ADN , Células Cultivadas , Lisina/metabolismo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA
...