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1.
Sci Rep ; 14(1): 18714, 2024 08 12.
Artículo en Inglés | MEDLINE | ID: mdl-39134702

RESUMEN

Chronic histiocytic intervillositis (CHI) is a recurrent placental lesion where maternal macrophages infiltrate the intervillous space. Its cause is unknown, though due to similarities to rejected allografts one hypothesis is that CHI represents maternal-fetal rejection. Here, virtual crossmatching was applied to healthy pregnancies and those with a history of CHI. Anti-HLA antibodies, measured by Luminex, were present in slightly more controls than CHI (8/17 (47.1%) vs 5/14 (35.7%)), but there was no significant difference in levels of sensitisation or fetal specific antibodies. Quantification of immunohistochemical staining for HLA-Class II was increased in syncytiotrophoblast of placentas with CHI (Grade 0.44 [IQR 0.1-0.7]) compared to healthy controls (0.06 [IQR 0-0.2]) and subsequent pregnancies (0.13 [IQR 0-0.3]) (P = 0.0004). HLA-Class II expression was positively related both to the severity of CHI (r = 0.67) and C4d deposition (r = 0.48). There was no difference in overall C4d and HLA-Class I immunostaining. Though increased anti-HLA antibodies were not evident in CHI, increased expression of HLA-Class II at the maternal-fetal interface suggests that they may be relevant in its pathogenesis. Further investigation of antibodies immediately after diagnosis is warranted in a larger cohort of CHI cases to better understand the role of HLA in its pathophysiology.


Asunto(s)
Antígenos de Histocompatibilidad Clase II , Humanos , Femenino , Embarazo , Adulto , Antígenos de Histocompatibilidad Clase II/metabolismo , Placenta/patología , Placenta/metabolismo , Placenta/inmunología , Regulación hacia Arriba , Enfermedades Placentarias/patología , Enfermedades Placentarias/inmunología , Enfermedades Placentarias/metabolismo , Vellosidades Coriónicas/metabolismo , Vellosidades Coriónicas/patología , Vellosidades Coriónicas/inmunología , Trofoblastos/metabolismo , Trofoblastos/patología , Trofoblastos/inmunología , Enfermedad Crónica
2.
Bull Exp Biol Med ; 177(3): 389-394, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-39134814

RESUMEN

A comparative study was carried out to analyze the number of syncytial knots and the intensity of expression of vascular endothelial growth factor (VEGF) in the villi of the monochorionic diamniotic placenta in pregnancies complicated by the syndrome of selective fetal growth restriction (sFGR). We performed a morphological analysis of 32 monochorionic diamniotic placentas after term delivery which were divided into two groups. The main group included the placentas of 15 puerperas whose pregnancies were complicated by sFGR. The control group included twin placentas of 17 puerperas without signs of sFGR. The number of syncytial knots was determined by histological studies, and the levels of VEGF expression in syncytiotrophoblast and capillary endotheliocytes of the placental villi were determined by immunohistochemical studies. The study showed an increase in the number of syncytial knots in the villi of the placental part of the fetus with sFGR which indicated the development of preplacental hypoxia. A significant increase in the level of VEGF expression in the syncytiotrophoblast and vascular endothelium of the villi should be considered as a manifestation of a compensatory adaptational response to hypoxia, though it is insufficient to prevent the development of sFGR.


Asunto(s)
Vellosidades Coriónicas , Retardo del Crecimiento Fetal , Placenta , Trofoblastos , Factor A de Crecimiento Endotelial Vascular , Humanos , Femenino , Embarazo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Retardo del Crecimiento Fetal/metabolismo , Retardo del Crecimiento Fetal/patología , Vellosidades Coriónicas/metabolismo , Vellosidades Coriónicas/patología , Trofoblastos/metabolismo , Trofoblastos/patología , Placenta/metabolismo , Placenta/patología , Adulto
3.
Biomolecules ; 14(7)2024 Jul 10.
Artículo en Inglés | MEDLINE | ID: mdl-39062540

RESUMEN

The migration, proliferation, and apoptosis of trophoblastic cells play a crucial role in ensuring the effective preservation of pregnancy at the maternal-fetal interface. Any deviations in the structure and function of these cells might potentially result in the development of numerous pregnancy-related disorders, including missed abortion (MA). This study involved the examination of semaphorin 4A (SEMA4A) expression in missed abortion (n = 18) and normal early pregnancy (n = 18) villus. The findings of this study indicate a statistically significant decrease in the expression of SEMA4A in the villi of individuals diagnosed with missed abortion, as compared to the control group. The results of our vitro study showed that SEMA4A promoted the migration and proliferation of trophoblast cells and inhibited their apoptosis. Subsequent studies have shown that SEMA4A may be involved in regulating p-STAT3/STAT3, MMP9, bcl-2, and BAX levels. In summary, the findings of this study indicate a correlation between the decreased level of SEMA4A in chorionic villi and missed abortion. These results offer novel theoretical insights into the proper implantation and development of SEMA4A embryos at the maternal-fetal interface.


Asunto(s)
Apoptosis , Proliferación Celular , Factor de Transcripción STAT3 , Semaforinas , Transducción de Señal , Trofoblastos , Humanos , Femenino , Trofoblastos/metabolismo , Embarazo , Semaforinas/metabolismo , Semaforinas/genética , Factor de Transcripción STAT3/metabolismo , Adulto , Movimiento Celular , Vellosidades Coriónicas/metabolismo , Aborto Retenido/metabolismo , Metaloproteinasa 9 de la Matriz/metabolismo
4.
Ann Clin Lab Sci ; 54(3): 289-298, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-39048170

RESUMEN

OBJECTIVE: This retrospective analysis compares the diagnostic value of placental large vessel (global, partial) and distal villous (complete, segmental) fetal vascular malperfusion (FVM), remote/established, recent and on-going. METHODS: 24 independent abnormal clinical and 46 placental phenotypes were retrospectively statistically analyzed among 1002 consecutive cases, mostly with congenital anomalies in which CD34 immunostaining was performed. Group A: 398 cases without distal FVM and none or up to two large vessels FVM lesions. Group B: 221 cases with distal villous FVM without clustered endothelial fragmentation by CD34 immunostain. Group C: 145 cases with clustered endothelial fragmentation by CD34 immunostain but no clustered sclerotic or mineralized distal villi. Group D: 163 cases with coexistence of distal villous lesions of Group B and Group C. Group E: 75 cases with three or four lesions of large vessel FVM, but no distal villous FVM lesions. RESULTS: Established and/or remote FVM had clinical/placental associations similar to those of recent FVM, but on-going FVM was most commonly high grade and associated with preterm pregnancies, stillbirth, and fetal growth restriction. Large vessel FVM usually occurs in advanced third trimester pregnancies with fetal congenital anomalies, villitis of unknown etiology, and intervillous thrombi but no direct association with abnormal fetal condition. CONCLUSION: FVM was the most common pattern of placental injury in this material. Proximal FVM was more common than distal FVM, suggesting the sequence of occurrence and the likely umbilical cord compression etiology. CD34 immunostaining doubles the sensitivity of placental examination and frequently upgrades the FVM, making it an important adjunct to placental histology.


Asunto(s)
Placenta , Humanos , Femenino , Embarazo , Placenta/patología , Placenta/irrigación sanguínea , Estudios Retrospectivos , Adulto , Enfermedades Placentarias/patología , Antígenos CD34/metabolismo , Feto/patología , Vellosidades Coriónicas/patología , Vellosidades Coriónicas/irrigación sanguínea , Relevancia Clínica
5.
PeerJ ; 12: e17616, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38952966

RESUMEN

Background: Mesenchymal stem cells (MSCs) are increasingly recognized for their regenerative potential. However, their clinical application is hindered by their inherent variability, which is influenced by various factors, such as the tissue source, culture conditions, and passage number. Methods: MSCs were sourced from clinically relevant tissues, including adipose tissue-derived MSCs (ADMSCs, n = 2), chorionic villi-derived MSCs (CMMSCs, n = 2), amniotic membrane-derived MSCs (AMMSCs, n = 3), and umbilical cord-derived MSCs (UCMSCs, n = 3). Passages included the umbilical cord at P0 (UCMSCP0, n = 2), P3 (UCMSCP3, n = 2), and P5 (UCMSCP5, n = 2) as well as the umbilical cord at P5 cultured under low-oxygen conditions (UCMSCP5L, n = 2). Results: We observed that MSCs from different tissue origins clustered into six distinct functional subpopulations, each with varying proportions. Notably, ADMSCs exhibited a higher proportion of subpopulations associated with vascular regeneration, suggesting that they are beneficial for applications in vascular regeneration. Additionally, CMMSCs had a high proportion of subpopulations associated with reproductive processes. UCMSCP5 and UCMSCP5L had higher proportions of subpopulations related to female reproductive function than those for earlier passages. Furthermore, UCMSCP5L, cultured under low-oxygen (hypoxic) conditions, had a high proportion of subpopulations associated with pro-angiogenic characteristics, with implications for optimizing vascular regeneration. Conclusions: This study revealed variation in the distribution of MSC subpopulations among different tissue sources, passages, and culture conditions, including differences in functions related to vascular and reproductive system regeneration. These findings hold promise for personalized regenerative medicine and may lead to more effective clinical treatments across a spectrum of medical conditions.


Asunto(s)
Tejido Adiposo , Células Madre Mesenquimatosas , Cordón Umbilical , Células Madre Mesenquimatosas/citología , Células Madre Mesenquimatosas/fisiología , Humanos , Cordón Umbilical/citología , Femenino , Tejido Adiposo/citología , Células Cultivadas , Vellosidades Coriónicas/fisiología , Amnios/citología , Diferenciación Celular
6.
Am J Reprod Immunol ; 92(1): e13898, 2024 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-38973779

RESUMEN

INTRODUCTION: Chronic histiocytic intervillositis (CHI) is a rare inflammatory placental disease characterized by diffuse infiltration of monocytes into the intervillous space and is associated with adverse pregnancy outcomes. No treatment is currently validated and although in some small reports, steroids with hydroxychloroquine have been described. There are no data for other therapies in refractory cases. PATIENTS AND METHODS: We here report four cases of patients with a history of CHI treated with immunoglobulins during a subsequent pregnancy. The four patients with recurrent CHI had failed to previous immunomodulatory therapies with steroids and hydroxychloroquine. All patients had at least four pregnancy losses with histopathological confirmation of CHI for at least one pregnancy loss. The usual pregnancy-loss etiology screening and immunological screening were negative for all the patients. RESULTS: For three patients, intravenous immunoglobulins were initiated at the ßHCG positivity at 1 g/kg every 15 days until delivery. In one case with combined therapy since the beginning of the pregnancy, intravenous immunoglobulins were introduced at 20 WG because of severe growth restriction. Two patients had live births at 36 WG and one patient at 39 WG. One patient, who presented early first-trimester hypertension and severe placental lesions, failed to intravenous immunoglobulins and had a pregnancy loss at 15 WG. CONCLUSION: This is the first report demonstrating the potential benefit of intravenous immunoglobulins in recurrent chronic intervillositis. Larger studies are needed to confirm this potential benefit for patients presenting severe cases of recurrent CHI.


Asunto(s)
Inmunoglobulinas Intravenosas , Enfermedades Placentarias , Humanos , Femenino , Embarazo , Inmunoglobulinas Intravenosas/uso terapéutico , Adulto , Enfermedades Placentarias/tratamiento farmacológico , Enfermedades Placentarias/patología , Enfermedad Crónica , Vellosidades Coriónicas/patología , Recurrencia , Placenta/patología , Resultado del Embarazo
7.
J Reprod Immunol ; 164: 104296, 2024 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-38972269

RESUMEN

Preeclampsia is a disorder of pregnancy characterized by endothelial dysfunction, abnormal placentation, systemic inflammation, and altered immune reaction. The aim of this study was to investigate the immune checkpoint molecules TIM-3 and Gal-9 on macrophages and Hofbauer cells (HBC) in the placenta of preeclampsia patients. Immunohistochemistry and Immunofluorescence was used to characterize the expression of the macrophage markers CD68 and CD163, CK7 and the proteins TIM-3 and Gal-9 in the placentas of preeclampsia patients comparing it to the placentas of healthy pregnancies. Double immunofluorescence staining (TIM-3 with CD3/CD19/CD56) was used to analyze the TIM-3 expression on other immune cells (T cells, B cells, NK cells) within the chorionic villi. The expression of TIM-3 on decidual macrophages did not significantly differ between the preeclamptic and the control group (p = 0.487). When looking at the different offspring we saw an upregulation of TIM-3 expression on decidual macrophages in preeclamptic placentas with female offspring (p = 0.049). On Hofbauer cells within the chorionic villi, the TIM-3 expression was significantly downregulated in preeclamptic cases without a sex-specific difference (p < 0.001). Looking at the protein Gal-9 the expression was proven to be downregulated both, on decidual macrophages (p = 0.003) and on Hofbauer cells (p = 0.002) within preeclamptic placentas compared to healthy controls. This was only significant in male offspring (p < 0.001 and p = 0.013) but not in female offspring (p = 0.360 and p = 0.068). While TIM-3 expression within the extravillious trophoblast and the syncytiotrophoblast was significantly downregulated (p < 0.001 and p = 0.012) in preeclampsia, the expression of Gal-9 was upregulated in (p < 0.001 and p < 0.001) compared to healthy controls. The local variations of the immune checkpoint molecules TIM-3 and Gal-9 in the placenta may contribute to the inflammation observed in preeclamptic patients. It could therefore contribute to the pathogenesis and be an important target in the treatment of preeclampsia.


Asunto(s)
Galectinas , Receptor 2 Celular del Virus de la Hepatitis A , Macrófagos , Placenta , Preeclampsia , Humanos , Embarazo , Receptor 2 Celular del Virus de la Hepatitis A/metabolismo , Femenino , Preeclampsia/inmunología , Preeclampsia/metabolismo , Preeclampsia/patología , Macrófagos/inmunología , Macrófagos/metabolismo , Galectinas/metabolismo , Adulto , Placenta/inmunología , Placenta/metabolismo , Placenta/patología , Antígenos CD/metabolismo , Antígenos de Diferenciación Mielomonocítica/metabolismo , Receptores de Superficie Celular/metabolismo , Vellosidades Coriónicas/inmunología , Vellosidades Coriónicas/metabolismo , Vellosidades Coriónicas/patología , Masculino
8.
Environ Res ; 257: 119165, 2024 Sep 15.
Artículo en Inglés | MEDLINE | ID: mdl-38759774

RESUMEN

Rare earth elements (REEs) exposure during pregnancy may increase the risk of unexplained spontaneous abortion. However, the association between REEs intrauterine exposure and unexplained spontaneous abortion had yet to be studied. In order to conduct this large case-control study, we thus collected chorionic villus from 641 unexplained spontaneous abortion and 299 control pregnant women and detected the concentrations of 15 REEs by inductively coupled plasma mass spectrometer (ICP-MS). Because the detection rates of 10 REEs were less than 80%, the remaining 5 REEs, which were lanthanum (La), cerium (Ce), praseodymium (Pr), neodymium (Nd) and yttrium (Y), underwent to further analysis. The association between 5 REEs and unexplained spontaneous abortion was assessed by using the logistic regression, bayesian kernel regression (BKMR) and weighted quantile sum regression (WQS) models. In the adjusted logistic regression model, Pr, Nd and Y enhanced the incidence of unexplained spontaneous abortion in a dose-dependent way and Ce increased the risk only at high concentration group. The result of BKMR model demonstrated that the risk of unexplained spontaneous abortion increased as the percentile of five mixed REEs increased. Y and Nd were both significantly associated with an increased incidence of unexplained spontaneous abortion, but La was correlated with a decrease in the risk of unexplained spontaneous abortion. Pr was substantially associated with an increase in the risk of unexplained spontaneous abortion when other REEs concentrations were fixed at the 25th and 50th percentiles. According to WQS regression analysis, the WQS index was significantly associated with unexplained spontaneous abortion (OR = 3.75, 95% CI:2.40-5.86). Y had the highest weight, followed by Nd and Pr, which was consistent with the analysis results of our other two models. In short, intrauterine exposure to REEs was associated with an increased risk of unexplained spontaneous abortion, with Y, Nd and Pr perhaps playing an essential role.


Asunto(s)
Aborto Espontáneo , Metales de Tierras Raras , Aborto Espontáneo/epidemiología , Aborto Espontáneo/inducido químicamente , Femenino , Humanos , Embarazo , Metales de Tierras Raras/análisis , Estudios de Casos y Controles , Adulto , Vellosidades Coriónicas , Adulto Joven , Modelos Logísticos
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.
Stem Cells Transl Med ; 13(7): 693-710, 2024 Jul 15.
Artículo en Inglés | MEDLINE | ID: mdl-38584493

RESUMEN

The environment created during embryogenesis contributes to reducing aberrations that drive structural malformations and tumorigenesis. In this study, we investigate the anti-cancer effect of mesenchymal stem cells (MSCs) derived from 2 different gestational tissues, the amniotic fluid (AF) and the chorionic villi (CV), with emphasis on their secretome. Transcriptomic analysis was performed on patient-derived AF- and CV-MSCs collected during prenatal diagnosis and identified both mRNAs and lncRNAs, involved in tissue homeostasis and inhibiting biological processes associated with the etiology of aggressive cancers while regulating immune pathways shown to be important in chronic disorders. Secretome enrichment analysis also identified soluble moieties involved in target cell regulation, tissue homeostasis, and cancer cell inhibition through the highlighted Wnt, TNF, and TGF-ß signaling pathways. Transcriptomic data were experimentally confirmed through in vitro assays, by evaluating the anti-cancer effect of the media conditioned by AF- and CV-MSCs and the exosomes derived from them on ovarian cancer cells, revealing inhibitory effects in 2D (by reducing cell viability and inducing apoptosis) and in 3D conditions (by negatively interfering with spheroid formation). These data provide molecular insights into the potential role of gestational tissues-derived MSCs as source of anti-cancer factors, paving the way for the development of therapeutics to create a pro-regenerative environment for tissue restoration following injury, disease, or against degenerative disorders.


Asunto(s)
Células Madre Mesenquimatosas , Humanos , Células Madre Mesenquimatosas/metabolismo , Femenino , Secretoma/metabolismo , Embarazo , Transcriptoma , Perfilación de la Expresión Génica , Exosomas/metabolismo , Vellosidades Coriónicas/metabolismo , Líquido Amniótico/metabolismo , Líquido Amniótico/citología , Línea Celular Tumoral
11.
Biol Lett ; 20(3): 20240016, 2024 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-38531417

RESUMEN

Despite having a single evolutionary origin and conserved function, the mammalian placenta exhibits radical structural diversity. The evolutionary drivers and functional consequences of placental structural diversity are poorly understood. Humans and equids both display treelike placental villi, however these villi evolved independently and exhibit starkly different levels of invasiveness into maternal tissue (i.e. the number of maternal tissue layers between placental tissue and maternal blood). The villi in these species therefore serve as a compelling evolutionary case study to explore whether placentas have developed structural adaptations to respond to the challenge of reduced nutrient availability in less invasive placentas. Here, we use three-dimensional X-ray microfocus computed tomography and electron microscopy to quantitatively evaluate key structures involved in exchange in human and equid placental villi. We find that equid villi have a higher surface area to volume ratio and deeper trophoblastic vessel indentation than human villi. Using illustrative computational models, we propose that these structural adaptations have evolved in equids to boost nutrient transfer to compensate for reduced invasiveness into maternal tissue. We discuss these findings in relation to the 'maternal-fetal conflict hypothesis' of placental evolution.


Asunto(s)
Vellosidades Coriónicas , Placenta , Animales , Embarazo , Femenino , Humanos , Mamíferos
12.
Biol Reprod ; 111(1): 135-147, 2024 Jul 12.
Artículo en Inglés | MEDLINE | ID: mdl-38401166

RESUMEN

OBJECTIVE: This study aimed to explore the specific pathways by which HOX transcript antisense intergenic RNA contributes to the pathogenesis of unexplained recurrent spontaneous abortion. METHODS: Real-time quantitative PCR was employed to assess the differential expression levels of HOX transcript antisense intergenic RNA in chorionic villi tissues from unexplained recurrent spontaneous abortion patients and women with voluntarily terminated pregnancies. HTR-8/SVneo served as a cellular model. Knockdown and overexpression of HOX transcript antisense intergenic RNA in the cells were achieved through siRNA transfection and pcDNA3.1 transfection, respectively. Cell viability, migration, and invasion were evaluated using cell counting kit-8, scratch, and Transwell assays, respectively. The interaction among the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 axis was predicted through bioinformatics analysis and confirmed through in vitro experiments. Furthermore, the regulatory effects of the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 signaling axis on cellular behaviors were validated in HTR-8/SVneo cells. RESULTS: We found that HOX transcript antisense intergenic RNA was downregulated in chorionic villi tissues from unexplained recurrent spontaneous abortion patients. Overexpression of HOX transcript antisense intergenic RNA significantly enhanced the viability, migration, and invasion of HTR-8/SVneo cells, while knockdown of HOX transcript antisense intergenic RNA had the opposite effects. We further confirmed the regulatory effect of the HOX transcript antisense intergenic RNA /miR-1277-5p/fibrillin 2 signaling axis in unexplained recurrent spontaneous abortion. Specifically, HOX transcript antisense intergenic RNA and fibrillin 2 were found to reduce the risk of unexplained recurrent spontaneous abortion by enhancing cell viability, migration, and invasion, whereas miR-1277-5p exerted the opposite effects. CONCLUSION: HOX transcript antisense intergenic RNA promotes unexplained recurrent spontaneous abortion development by targeting inhibition of miR-1277-5p/fibrillin 2 axis.


Asunto(s)
Aborto Habitual , Movimiento Celular , MicroARNs , ARN Largo no Codificante , Transducción de Señal , Humanos , MicroARNs/genética , MicroARNs/metabolismo , Femenino , Aborto Habitual/genética , Aborto Habitual/metabolismo , Aborto Habitual/patología , ARN Largo no Codificante/genética , ARN Largo no Codificante/metabolismo , Embarazo , Fibrilina-2/genética , Fibrilina-2/metabolismo , Adulto , Proliferación Celular , Línea Celular , Trofoblastos/metabolismo , Trofoblastos/fisiología , Vellosidades Coriónicas/metabolismo
13.
Eur J Obstet Gynecol Reprod Biol ; 292: 125-132, 2024 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-37995528

RESUMEN

MPVFD (Massive perivillous fibrin deposition) is placental lesion characterized by extensive massive deposits of fibrin in the intervillous space, extending over at least 25 % of the placental volume. Currently, this pathology can only be detected through histopathological examination of the placenta after a pregnancy has ended. The underlying mechanisms are poorly studied, there is no biomarker available for the diagnosis of MPVFD and treatment protocols are experimental and still lacking. The objective of this study is to systematically review the literature on the associated clinicopathologic features, treatment, and prognosis of MPVFD. We ended up with 17 studies, of these 12 studies were considered relevant for this article and included in the final analysis. All studies reporting MPVFD are retrospective. MPVFD is associated with recurrent miscarriage, intra uterine fetal death (IUFD), intra uterine growth restriction (IUGR) and preterm delivery. The prevalence in pregnancies with a delivery after 22 weeks of gestation was at 1.1 % and even higher to 2.7 % in recurrent early miscarriages. The reported risk of fetal death in MPVFD ranges mainly from 15 to 80 %. Preterm delivery is spontaneous in 50 to 70 % of cases and induced by of a severe intrauterine growth restriction (IUGR) in 30 to 50 % of cases depending on the study. Its causes and treatment are still poorly understood, although several avenues have been explored. This review summarizes current understanding of the prevalence, diagnostic features, clinical consequences, immune pathology, and potential prophylaxis against recurrence in this chronic inflammatory placental syndrome.


Asunto(s)
Aborto Habitual , Enfermedades Placentarias , Nacimiento Prematuro , Recién Nacido , Embarazo , Femenino , Humanos , Placenta/patología , Enfermedades Placentarias/diagnóstico , Enfermedades Placentarias/terapia , Enfermedades Placentarias/patología , Vellosidades Coriónicas/patología , Estudios Retrospectivos , Nacimiento Prematuro/patología , Muerte Fetal/etiología , Aborto Habitual/diagnóstico , Aborto Habitual/etiología , Aborto Habitual/prevención & control , Retardo del Crecimiento Fetal/etiología , Fibrina
14.
Reprod Sci ; 31(4): 997-1005, 2024 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-37973775

RESUMEN

Tumor necrosis factor-α (TNF-α) antagonists are highly effective in controlling autoimmune diseases. This has led to speculation that they might also be useful in treating inflammatory placental conditions, such as chronic villitis of unknown etiology (VUE). VUE affects 10-15% of term placentas and is associated with recurrent fetal growth restriction (FGR) and pregnancy loss. We aimed to evaluate outcomes in patients with autoimmune diseases with and without anti-TNF-α biologic exposure during gestation. This retrospective cohort study compared pregnant women with autoimmune disease taking anti-TNF-α biologics (n = 89) to pregnant women with autoimmune disease but not taking a biologic (n = 53). We extracted data on all patients meeting our inclusion criteria over a 20-year period. Our primary outcome was the diagnosis of VUE by histology. Our secondary outcomes were maternal and neonatal complications such as preeclampsia, FGR, and neonatal intensive care admission. Kruskal-Wallis and chi-squared tests were performed as appropriate for statistical analysis. Maternal characteristics were comparable between groups, and there was no increase in adverse pregnancy outcomes based on anti-TNF-α treatment. Exposure to anti-TNF-α therapy had no significant effect on the incidence of VUE or other obstetric complications. Within the cohort exposed to anti-TNF-α biologics during pregnancy, the rate of VUE was 9.3%, which is comparable to the reported general population risk. Our data support the safety profile of biologic use in pregnancy.


Asunto(s)
Enfermedades Autoinmunes , Productos Biológicos , Corioamnionitis , Enfermedades Placentarias , Recién Nacido , Humanos , Embarazo , Femenino , Placenta/patología , Inhibidores del Factor de Necrosis Tumoral/efectos adversos , Enfermedades Placentarias/diagnóstico , Vellosidades Coriónicas/patología , Estudios Retrospectivos , Resultado del Embarazo , Retardo del Crecimiento Fetal/inducido químicamente , Retardo del Crecimiento Fetal/patología , Enfermedades Autoinmunes/diagnóstico , Enfermedades Autoinmunes/tratamiento farmacológico , Enfermedades Autoinmunes/complicaciones , Productos Biológicos/efectos adversos
15.
Placenta ; 145: 139-142, 2024 01.
Artículo en Inglés | MEDLINE | ID: mdl-38134546

RESUMEN

Placentae collected from elective terminations during the first trimester are commonly used as control samples in research. However, it is widely acknowledged that many complications of pregnancies can occur or originate during the early stage of gestation. This raises the question that the placentae collected from the first trimester may not accurately reflect normal placental conditions. In this study, 95 placentae were collected from elective terminations and histology was performed. Out of these, 53 placentae (56 %) exhibited the typical structure of placental villi, indicating normal development. However, 42 placentae (44 %) showed placental hydrops, with varying degrees of severity (mild, moderate, or severe). Placental hydrops has been linked to several complicated pregnancies in the later stages of gestation. Our findings suggest that the development of pregnancy pathologies could start in the first trimester, as observed by the presence of hydrops. Placental researchers should be aware of when using first-trimester placentae from termination as controls in studies. However, it remains unclear whether pathological morphologies resolve or ameliorate as the pregnancy progression or whether such placentae continue to have such pathology, but clinical symptoms/signs do not manifest.


Asunto(s)
Enfermedades Placentarias , Placenta , Embarazo , Femenino , Humanos , Primer Trimestre del Embarazo , Vellosidades Coriónicas , Edema
16.
Sci Rep ; 13(1): 21719, 2023 12 11.
Artículo en Inglés | MEDLINE | ID: mdl-38081877

RESUMEN

Chromosomal abnormalities are the most common etiology of early spontaneous miscarriage. However, traditional karyotyping of chorionic villus samples (CVSs) is limited by cell culture and its low resolution. The objective of our study was to investigate the efficiency of molecular karyotyping technology for genetic diagnosis of early missed abortion tissues. Chromosome analysis of 1191 abortion CVSs in early pregnancy was conducted from August 2016 to June 2021; 463 cases were conducted via copy-number variations sequencing (CNV-seq)/quantitative fluorescent-polymerase chain reaction (QF-PCR) and 728 cases were conducted using SNP array. Clinically significant CNVs of CVSs were identified to clarify the cause of miscarriage and to guide the couples' subsequent pregnancies. Among these, 31 cases with significant maternal cell contamination were removed from the study. Among the remaining 1160 samples, 751 cases (64.7%) with genetic abnormalities were identified, of which, 531 (45.8%) were single aneuploidies, 31 (2.7%) were multiple aneuploidies, 50 (4.3%) were polyploidies, 54 (4.7%) were partial aneuploidies, 77 (6.6%) had submicroscopic CNVs (including 25 with clinically significant CNVs and 52 had variants of uncertain significance), and 8 cases (0.7%) were uniparental disomies. Our study suggests that both SNP array and CNV-seq/QF-PCR are reliable, robust, and high-resolution technologies for genetic diagnosis of miscarriage.


Asunto(s)
Aborto Retenido , Aborto Espontáneo , Embarazo , Femenino , Humanos , Aborto Espontáneo/genética , Aborto Retenido/genética , Vellosidades Coriónicas , Aberraciones Cromosómicas , Aneuploidia , Variaciones en el Número de Copia de ADN/genética
17.
Placenta ; 144: 23-28, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37952366

RESUMEN

INTRODUCTION: Villitis of unknown etiology (VUE) is a histopathological lesion associated with adverse neonatal outcomes. We seek to define the obscure relationship between the severity and distribution of VUE and adverse neonatal outcomes. METHODS: A retrospective chart review was conducted of pathologic findings from singleton placentas diagnosed with VUE between 2013 and 2019. Control placentas were matched 1:1 for gestational age and presence/absence of fetal IUGR. Neonatal outcomes of interest included: newborn resuscitation, NICU admission, Apgar scores and cord blood acidosis. Odds ratio and 95 % confidence intervals were calculated with controls as the reference. RESULTS: 452 placentas were included. 35 % of pregnancies were complicated by IUGR. When analyzed by severity (low-grade: OR = 4.75 [2.86-8.14]; high-grade: OR = 4.76 [2.71-8.79]) and distribution (focal: OR = 5.24 [2.87-10.17]; multifocal: OR = 4.90 [2.90-8.59]), VUE was significantly associated with need for newborn resuscitation. No other neonatal outcomes of interest were significantly associated with VUE diagnosis. DISCUSSION: We determined a statistically significant association between VUE severity and distribution and the need for newborn resuscitation. VUE lesions were not associated with any additional neonatal outcomes of interest. Further studies with larger sample sizes are required to confirm these associations for obstetric and neonatal case management.


Asunto(s)
Corioamnionitis , Enfermedades Placentarias , Embarazo , Femenino , Recién Nacido , Humanos , Vellosidades Coriónicas/patología , Enfermedades Placentarias/epidemiología , Enfermedades Placentarias/etiología , Enfermedades Placentarias/patología , Estudios Retrospectivos , Ontario/epidemiología , Placenta/patología , Corioamnionitis/patología
18.
Reprod Biol Endocrinol ; 21(1): 108, 2023 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-37968664

RESUMEN

BACKGROUND: It has been long known that thyroid hormone regulates placental villi development, which is associated with the occurrence of miscarriage. However, whether abnormal thyroid hormone metabolism and transport in placental villi are involved in miscarriage is still to be verified. METHODS: Placental villi of elective terminations of pregnancies (ETPs) and miscarriage were collected. Proliferative activity and apoptosis of villi trophoblasts and angiogenesis were detected by TUNEL and immunochemistry. The expressions of thyroid hormone receptors (THRs), transthyretin (TTR), monocarboxylate transporter 8 (MCT8), organic anion transporting polypeptides 1A1 (OATP1A1), deiodinase 2 (Dio2) and Dio3 were examined by RT-PCR, Western blot, immunohistochemistry and immunofluorescence. JEG3 cell was treated with iopanoic acid (IOP), an inhibitor of Dio2 activity, the expressions of Dio2, placenta growth factor (PLGF) and sFlt1 were detected by RT-PCR and Western blot. RESULTS: Cell proliferation was suppressed and apoptosis was increased in placental villi cytotrophoblasts of miscarriage. CD34+ vessel number and vascular endothelial growth factor (VEGF) protein abundance were decreased in miscarriage. In miscarriage group, the gene expression of Dio2, Dio3, TTR and THRα, but not THRß, MCT8 and OATP1A1, were downregulated. The protein abundances of TTR and THRα were downregulated in miscarriage group, but not THRß. The protein abundance of Dio2 in miscarriage villi was decreased compared with that in ETP. In JEG3 cells, the gene expression of PLGF was decreased and the expression of sFlt1 was increased in IOP treatment; The protein abundance of Dio2 was downregulated but the gene expression of Dio2 was unaffected in IOP treatment. CONCLUSION: Thyroid hormone transport and metabolism in miscarriage were disturbed and may impaired angiogenesis of placental villi, which was associated with the occurrence of miscarriage.


Asunto(s)
Aborto Espontáneo , Receptor 1 de Factores de Crecimiento Endotelial Vascular , Humanos , Embarazo , Femenino , Aborto Espontáneo/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo , Vellosidades Coriónicas/metabolismo , Línea Celular Tumoral , Placenta/metabolismo , Hormonas Tiroideas/metabolismo
19.
Adv Healthc Mater ; 12(32): e2301428, 2023 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-37830445

RESUMEN

The early-stage placental barrier is characterized by a lack of fetal circulation and by a thick trophoblastic barrier, whereas the later-stage placenta consists of vascularized chorionic villi encased in a thin, differentiated trophoblast layer, ideal for nutrient transport. In this work, predictive models of early- and late-stage placental transport are created using blastocyst-derived placental stem cells (PSCs) by modulating PSC differentiation and model vascularization. PSC differentiation results in a thinner, fused trophoblast layer, as well as an increase in human chorionic gonadotropin secretion, barrier permeability, and secretion of certain inflammatory cytokines, which are consistent with in vivo findings. Further, gene expression confirms this shift toward a differentiated trophoblast subtype. Vascularization results in a molecule type- and size-dependent change in dextran and insulin permeability. These results demonstrate that trophoblast differentiation and vascularization have critical effects on placental barrier permeability and that this model can be used as a predictive measure to assess fetal toxicity of xenobiotic substances at different stages of pregnancy.


Asunto(s)
Placenta , Trofoblastos , Embarazo , Femenino , Humanos , Trofoblastos/metabolismo , Diferenciación Celular , Vellosidades Coriónicas/metabolismo , Células Madre
20.
Am J Reprod Immunol ; 90(4): e13777, 2023 10.
Artículo en Inglés | MEDLINE | ID: mdl-37766400

RESUMEN

PROBLEM: Congenital Trypanosoma cruzi (T. cruzi) infection has been associated with changes in the levels of TNF-α and IFN-γ during the pregnancy. Therefore, we propose to study the participation and dynamics of proinflammatory cytokines in the infection process of placental explants infected by T. cruzi in vitro. METHOD OF STUDY: Chorionic villous explants (CVE) obtained of human term placentas (n = 8) from normal pregnancies were cultured with 105 trypomastigotes/mL of Tulahuen strain DTU VI for 0, 2, 4, 16, 24, 48 and 72 h. Explants were treated with sulfasalazine (SULF) (5 mM) and N-acetyl-cysteine (NAC) (15 mM), as inhibitors molecules of NF-κB pathway, or LPS (1 µg/mL) for 24 and 72 h p.i. Motile trypomastigotes were counted in culture supernatants. Immunohistochemistry and ELISA for TNF-α, IFN-γ, IL-1ß, IL-4, and IL-10 were performed in CVE and culture supernatants respectively. The parasite load was measured by RT-qPCR. RESULTS: T. cruzi invades the chorionic villi from 4 h p.i. increasing significantly its DNA at 48 and 72 h p.i. of culture (parasite multiplication phase). They were detected in stromal cells, which was related to elevation of TNF-α, IL-1ß, IFN-γ, and IL-10. The inhibition of NF-κB activity in the explants decreased the production of the analyzed cytokines, showing elevated levels of T. cruzi DNA during the multiplication phase of the parasite. CONCLUSIONS: Placental tissue modifies the secretion of pro-inflammatory cytokines during the phase of parasite multiplication, but not during the invasion phase, which in turns modifies the level of infection via the signaling pathway NF-κB.


Asunto(s)
Enfermedad de Chagas , Trypanosoma cruzi , Embarazo , Femenino , Humanos , FN-kappa B , Vellosidades Coriónicas , Placenta , Interleucina-10 , Citocinas , Factor de Necrosis Tumoral alfa , Transducción de Señal
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