RESUMO
OBJECTIVE: The Hedgehog pathway is a fundamental signaling pathway in organogenesis. The expression patterns of the ligand Sonic Hedgehog (Shh) and key pathway components have been studied in many tissues but direct spatial comparisons across tissues with different cell compositions and structural organization are not common and could reveal tissue-specific differences in pathway dynamics. RESULTS: We directly compared the expression characteristics of Shh, and four genes with functional roles in signaling and whose expression levels serve as readouts of pathway activity in multiple tissues of the embryonic mouse head at embryonic day 15.5 by serial in situ hybridization. The four readout genes were the positive feedback regulator Gli1, and three negative feedback regulators, Patched1, Patched2, and Hedgehog Interacting Protein. While the relative abundance of Gli1 was similar across tissues, the relative expression levels and spatial distribution of Shh and the negative feedback regulators differed, suggesting that feedback regulation of hedgehog signaling is context dependent. This comparative analysis offers insight into how consistent pathway activity could be achieved in tissues with different morphologies and characteristics of ligand expression.
Assuntos
Cabeça/embriologia , Proteínas Hedgehog , Transdução de Sinais , Animais , Retroalimentação Fisiológica , Proteínas Hedgehog/genética , Camundongos , Proteína GLI1 em Dedos de Zinco/genéticaRESUMO
The Wnt pathway activates target genes by controlling the ß-catenin-T-cell factor (TCF) transcriptional complex during embryonic development and cancer. This pathway can be potentiated by R-spondins, a family of proteins that bind RNF43/ZNRF3 E3 ubiquitin ligases and LGR4/5 receptors to prevent Frizzled degradation. Here we demonstrate that, during Xenopus anteroposterior axis specification, Rspo2 functions as a Wnt antagonist, both morphologically and at the level of gene targets and pathway mediators. Unexpectedly, the binding to RNF43/ZNRF3 and LGR4/5 was not required for the Wnt inhibitory activity. Moreover, Rspo2 did not influence Dishevelled phosphorylation in response to Wnt ligands, suggesting that Frizzled activity is not affected. Further analysis indicated that the Wnt antagonism is due to the inhibitory effect of Rspo2 on TCF3/TCF7L1 phosphorylation that normally leads to target gene activation. Consistent with this mechanism, Rspo2 anteriorizing activity has been rescued in TCF3-depleted embryos. These observations suggest that Rspo2 is a context-specific regulator of TCF3 phosphorylation and Wnt signaling.
Assuntos
Padronização Corporal/efeitos dos fármacos , Peptídeos e Proteínas de Sinalização Intercelular/fisiologia , Fator 3 de Transcrição/antagonistas & inibidores , Via de Sinalização Wnt/efeitos dos fármacos , Proteínas de Xenopus/antagonistas & inibidores , Proteínas de Xenopus/fisiologia , Animais , Padronização Corporal/fisiologia , Embrião não Mamífero/anormalidades , Embrião não Mamífero/efeitos dos fármacos , Embrião não Mamífero/metabolismo , Desenvolvimento Embrionário/efeitos dos fármacos , Regulação da Expressão Gênica no Desenvolvimento/efeitos dos fármacos , Genes Reporter , Cabeça/embriologia , Fosforilação/efeitos dos fármacos , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Fator 3 de Transcrição/metabolismo , Proteínas de Xenopus/biossíntese , Proteínas de Xenopus/genética , Proteínas de Xenopus/metabolismo , Proteínas de Xenopus/farmacologia , Xenopus laevis/embriologiaRESUMO
The dynamics of multipotent neural crest cell differentiation and invasion as cells travel throughout the vertebrate embryo remain unclear. Here, we preserve spatial information to derive the transcriptional states of migrating neural crest cells and the cellular landscape of the first four chick cranial to cardiac branchial arches (BA1-4) using label-free, unsorted single-cell RNA sequencing. The faithful capture of branchial arch-specific genes led to identification of novel markers of migrating neural crest cells and 266 invasion genes common to all BA1-4 streams. Perturbation analysis of a small subset of invasion genes and time-lapse imaging identified their functional role to regulate neural crest cell behaviors. Comparison of the neural crest invasion signature to other cell invasion phenomena revealed a shared set of 45 genes, a subset of which showed direct relevance to human neuroblastoma cell lines analyzed after exposure to the in vivo chick embryonic neural crest microenvironment. Our data define an important spatio-temporal reference resource to address patterning of the vertebrate head and neck, and previously unidentified cell invasion genes with the potential for broad impact.
Assuntos
Região Branquial/crescimento & desenvolvimento , Cabeça/crescimento & desenvolvimento , Pescoço/crescimento & desenvolvimento , Crista Neural/crescimento & desenvolvimento , Animais , Padronização Corporal/genética , Região Branquial/embriologia , Diferenciação Celular/genética , Movimento Celular/genética , Microambiente Celular/genética , Embrião de Galinha , Embrião de Mamíferos , Embrião não Mamífero , Desenvolvimento Embrionário/genética , Cabeça/embriologia , Humanos , Mesoderma/crescimento & desenvolvimento , Células-Tronco Multipotentes/citologia , Pescoço/embriologia , Crista Neural/metabolismo , Neuroblastoma/genética , Neuroblastoma/patologia , Organogênese/genética , Microambiente Tumoral/genética , Vertebrados/genética , Vertebrados/crescimento & desenvolvimentoRESUMO
OBJECTIVES: To evaluate the accuracy of an automated three-dimensional (3D) ultrasound technique for fetal intracranial measurements compared with manual acquisition. METHODS: This was a prospective observational study of patients presenting for routine anatomical survey between 18 + 0 and 22 + 6 weeks' gestation. After providing informed consent, each patient underwent two consecutive ultrasound examinations of the fetal head, one by a sonographer and one by a physician. Each operator obtained manual measurements of the biparietal diameter (BPD), head circumference (HC), transcerebellar diameter (TCD), cisterna magna (CM) and posterior horn of the lateral ventricle (Vp), followed by automated measurements of these structures using an artificial intelligence-based tool, SonoCNS® Fetal Brain. Both operators repeated the automated approach until all five measurements were obtained in a single sweep, up to a maximum of three attempts. The accuracy of automated measurements was compared with that of manual measurements using intraclass correlation coefficients (ICC) by operator type, accounting for patient and ultrasound characteristics. RESULTS: One hundred and forty-three women were enrolled in the study. Median body mass index was 24.0 kg/m2 (interquartile range (IQR), 22.5-26.8 kg/m2 ) and median subcutaneous thickness was 1.6 cm (IQR, 1.3-2.0 cm). Fifteen (10%) patients had at least one prior Cesarean delivery, 17 (12%) had other abdominal surgery and 78 (55%) had an anterior placenta. Successful acquisition of the automated measurements was achieved on the first, second and third attempts in 70%, 22% and 3% of patients, respectively, by sonographers and in 76%, 16% and 3% of cases, respectively, by physicians. The automated algorithm was not able to identify and measure all five structures correctly in six (4%) and seven (5%) patients scanned by the sonographers and physicians, respectively. The ICCs reflected good reliability (0.80-0.88) of the automated compared with the manual approach for BPD and HC and poor to moderate reliability (0.23-0.50) for TCD, CM and Vp. Fetal lie, head position, placental location, maternal subcutaneous thickness and prior Cesarean section were not associated with the success or accuracy of the automated technique. CONCLUSIONS: Automated 3D ultrasound imaging of the fetal head using SonoCNS reliably identified and measured BPD and HC but was less consistent in accurately identifying and measuring TCD, CM and Vp. While these results are encouraging, further optimization of the automated technology is necessary prior to incorporation of the technique into routine sonographic protocols. © 2020 International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Biometria/métodos , Feto/diagnóstico por imagem , Cabeça/diagnóstico por imagem , Imageamento Tridimensional/métodos , Ultrassonografia Pré-Natal/métodos , Adulto , Inteligência Artificial , Feminino , Feto/embriologia , Idade Gestacional , Cabeça/embriologia , Humanos , Gravidez , Estudos Prospectivos , Reprodutibilidade dos TestesRESUMO
OBJECTIVES: The primary objective of this study was to assess whether fetuses with congenital heart disease (CHD) have smaller frontal brain areas compared with normal controls. The secondary objective was to evaluate whether there are any differences in frontal brain area between cases with different types of CHD, grouped according to their impact on hemodynamics. METHODS: This was a retrospective cross-sectional study, including 421 normal fetuses and 101 fetuses with isolated CHD evaluated between 20 and 39 gestational weeks at our fetal medicine and surgery unit in the period January 2016-December 2019. The study group was subdivided, according to the CHD hemodynamics, as follows: (1) hypoplastic left heart syndrome and other forms of functionally univentricular heart defect; (2) transposition of the great arteries; (3) conotruncal defects and other CHDs with large shunts; (4) right ventricular outflow tract obstruction, without a hypoplastic right ventricle; (5) left outflow tract obstruction; (6) others. The transventricular axial view of the fetal head was used as the reference view, on which the frontal lobe anteroposterior diameter (FAPD) and the occipitofrontal diameter (OFD) were measured, assuming the former to be representative of the area of the frontal lobes. The FAPD/OFD ratio was then calculated as FAPD/OFD × 100. These two variables (FAPD and FAPD/OFD ratio) were then evaluated and compared between the study and control groups. Adjustment for gestational age, both via multiple linear regression and by using a-posteriori matching based on the propensity score, was employed. RESULTS: In normal fetuses, FAPD showed a linear positive correlation with gestational age. In fetuses with CHD, the FAPD was shorter than in normal fetuses from the 20th gestational week onwards, with the difference increasing after 30 gestational weeks. FAPD/OFD ratio was significantly smaller in fetuses with CHD than in normal fetuses (P < 0.0001) at all gestational ages, with no apparent differences among the various CHD categories, all of which had smaller FAPD/OFD ratio compared with controls. CONCLUSIONS: Fetuses with CHD have a shorter FAPD and a smaller FAPD/OFD ratio compared with normal fetuses. This impaired growth of the frontal area of the brain seems to occur in all types of CHD, regardless of their impact on hemodynamics. © 2021 International Society of Ultrasound in Obstetrics and Gynecology.
Assuntos
Encéfalo/embriologia , Desenvolvimento Fetal/fisiologia , Lobo Frontal/embriologia , Cardiopatias Congênitas/embriologia , Adulto , Encéfalo/crescimento & desenvolvimento , Estudos de Casos e Controles , Estudos Transversais , Feminino , Feto/diagnóstico por imagem , Feto/embriologia , Feto/fisiopatologia , Lobo Frontal/diagnóstico por imagem , Lobo Frontal/crescimento & desenvolvimento , Idade Gestacional , Cabeça/diagnóstico por imagem , Cabeça/embriologia , Cardiopatias Congênitas/fisiopatologia , Hemodinâmica , Humanos , Modelos Lineares , Gravidez , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
OBJECTIVE: To describe the prenatal sonographic features and maternal biochemical markers in triploid pregnancies and to assess whether prenatal phenotype can determine genetic origin. METHODS: We performed a retrospective multicenter cohort study that included all triploid pregnancies diagnosed between 2000 and 2018 in two Fetal Medicine Units in Amsterdam. Fetal growth, presence of structural anomalies, extra-fetal anomalies, and maternal biochemical markers were retrieved. Asymmetrical intrauterine growth restriction was diagnosed when the head-to-abdominal circumference (HC/AC) ratio was >95th centile. Parental origin was analyzed via molecular genotyping in 46 cases (38.3%). RESULTS: One hundred and twenty triploid pregnancies were identified, of which 86 cases (71.6%) were detected before 18 weeks of gestation. Triploidy of maternal origin was found in 32 cases (69.6%) and was associated with asymmetrical growth restriction, a thin placenta, and low pregnancy-associated plasma protein A and free beta-human chorionic gonadotrophin (ß-hCG) levels. Triploidy of paternal origin was found in 14 cases (30.4%) and was associated with an increased nuchal translucency, placental molar changes, and a high free ß-hCG. Prospective prediction of the parental origin of the triploidy was made in 30 of the 46 cases based on phenotypical ultrasound presentation, and it was correct in all cases. CONCLUSION: Asymmetrical growth restriction with severe HC/AC discrepancy is pathognomonic of maternal triploidy. Placental molar changes indicate a paternal triploidy. Moreover, triploidy can present with an abnormal first trimester combined test, with serum levels on the extreme end. When available results of maternal serum markers can support the diagnosis of parental origin of the triploidy, an accurate assessment of the parental origin based on prenatal sonographic features is possible, making DNA analysis redundant.
Assuntos
Abdome/diagnóstico por imagem , Gonadotropina Coriônica Humana Subunidade beta/metabolismo , Retardo do Crescimento Fetal/diagnóstico por imagem , Genótipo , Cabeça/diagnóstico por imagem , Fenótipo , Placenta/diagnóstico por imagem , Proteína Plasmática A Associada à Gravidez/metabolismo , Triploidia , Abdome/embriologia , Aborto Induzido , Adulto , Feminino , Morte Fetal , Cabeça/embriologia , Humanos , Testes para Triagem do Soro Materno , Medição da Translucência Nucal , Tamanho do Órgão , Gravidez , Ultrassonografia Pré-NatalRESUMO
Along with the aorta-gonad-mesonephros region, the head is a site of hematopoietic stem and progenitor cell (HS/PC) development in the mouse embryo. Macrophages are present in both these embryonic hemogenic sites, and recent studies indicate a functional interaction of macrophages with hematopoietic cells as they are generated in the aorta. Whereas brain macrophages or "microglia" are known to affect neuronal patterning and vascular circuitry in the embryonic brain, it is unknown whether macrophages play a role in head hematopoiesis. Here, we characterize head macrophages and examine whether they affect the HS/PC output of the hindbrain-branchial arch (HBA) region of the mouse embryo. We show that HBA macrophages are CD45+F4/80+CD11b+Gr1- and express the macrophage-specific Csf1r-GFP reporter. In the HBA of chemokine receptor-deficient (Cx3cr1-/-) embryos, a reduction in erythropoiesis is concomitant with a decrease in HBA macrophage percentages. In cocultures, we show that head macrophages boost hematopoietic progenitor cell numbers from HBA endothelial cells > twofold, and that the proinflammatory factor tumor necrosis factor-α is produced by head macrophages and influences HBA hematopoiesis in vitro. Taken together, head macrophages play a positive role in HBA erythropoiesis and HS/PC expansion and/or maturation, acting as microenvironmental cellular regulators in hematopoietic development.
Assuntos
Embrião de Mamíferos/embriologia , Eritropoese/fisiologia , Cabeça/embriologia , Células-Tronco Hematopoéticas/metabolismo , Macrófagos/metabolismo , Animais , Embrião de Mamíferos/citologia , Células Endoteliais/citologia , Células Endoteliais/metabolismo , Feminino , Células-Tronco Hematopoéticas/citologia , Macrófagos/citologia , Masculino , Camundongos , Camundongos KnockoutRESUMO
Mammalian CEP55 (centrosomal protein 55 kDa) is a coiled-coil protein localized to the centrosome in interphase cells and is required for cytokinesis. A homozygous non-sense mutation in human CEP55 has been recently identified in perinatal lethal MARCH (multinucleated neurons, anhydramnios, renal dysplasia, cerebellar hypoplasia and hydranencephaly) syndrome. We have isolated zebrafish cep55 mutants defective in head morphology. The zebrafish cep55 gene was expressed in the head including the retina and the pectoral fin at 1 day post-fertilization (dpf), and extensive cell death was widely observed in the head and tail of the cep55 mutant. In the cep55 mutant, the anterior-posterior distance of the ventral pharyngeal arches was short, and retinal lamination was disorganized. Neural cells, such as islet1-positive cells and pax2-positive cells, and fli1b-positive vascular cells were reduced in the head of the cep55 mutant. Thus, we propose that the zebrafish cep55 mutant is a model organism for human MARCH syndrome.
Assuntos
Proteínas de Ciclo Celular/genética , Proteínas Nucleares/genética , Proteínas de Peixe-Zebra/genética , Peixe-Zebra/embriologia , Animais , Proteínas de Ciclo Celular/metabolismo , Centrossomo/metabolismo , Citocinese/genética , Cabeça/anormalidades , Cabeça/embriologia , Mutação , Proteínas Nucleares/metabolismo , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Peixe-Zebra/anormalidades , Peixe-Zebra/genética , Proteínas de Peixe-Zebra/metabolismoRESUMO
Chondroitin sulfate (CS) proteoglycan is a major component of the extracellular matrix and plays an important part in organogenesis. To elucidate the roles of CS for craniofacial development, we analyzed the craniofacial morphology in CS N-acetylgalactosaminyltransferase-1 (T1) gene knockout (KO) mice. T1KO mice showed the impaired intramembranous ossification in the skull, and the final skull shape of adult mice included a shorter face, higher and broader calvaria. Some of T1KO mice exhibited severe facial developmental defect, such as eye defects and cleft lip and palate, causing embryonic lethality. At the postnatal stages, T1KO mice with severely reduced CS amounts showed malocclusion, general skeletal dysplasia and skin hyperextension, closely resembling Ehlers-Danlos syndrome-like connective tissue disorders. The production of collagen type 1 was significantly downregulated in T1KO mice, and the deposition of CS-binding molecules, Wnt3a, was decreased with CS in extracellular matrices. The collagen fibers were irregular and aggregated, and connective tissues were dysorganized in the skin and calvaria of T1KO mice. These results suggest that CS regulates the shape of the craniofacial skeleton by modulating connective tissue organization and that the remarkable reduction of CS induces hypoplasia of intramembranous ossification and cartilage anomaly, resulting in skeletal dysplasia.
Assuntos
Anormalidades Craniofaciais/etiologia , Cabeça/anormalidades , N-Acetilgalactosaminiltransferases/genética , Animais , Animais Recém-Nascidos , Cartilagem/patologia , Sulfatos de Condroitina/metabolismo , Colágeno/genética , Colágeno/metabolismo , Anormalidades Craniofaciais/genética , Síndrome de Ehlers-Danlos/etiologia , Feminino , Cabeça/embriologia , Camundongos Knockout , N-Acetilgalactosaminiltransferases/metabolismo , Osteocondrodisplasias/etiologia , Osteogênese/genética , Gravidez , Proteína Wnt3A/genética , Proteína Wnt3A/metabolismoRESUMO
OBJECTIVE: To evaluate neonatal mortality and morbidity up to 6 months in neonates with congenital diaphragmatic hernia (CDH) with or without a hernia sac. METHODS: Seventy-two cases of isolated CDH were included in a retrospective single-center study between January 2010 and December 2016. Hernia sac was defined at the time of surgery or at postmortem examination if the neonate died before surgery. RESULTS: Seventeen newborns (23.6%) had a hernia sac. Survival at 6 months was significantly greater for isolated CDH with a hernia sac: 100% versus 63.6% (P = .003). High-frequency oscillatory ventilation was used significantly more in the no hernia sac group (P = .04). At surgery, the need for patch repair was significantly lower in the hernia sac group: 12% versus 50% (P = .005). The prenatal observed/expected lung-to-head ratio was significantly higher in the hernia sac group than in the no hernia sac group: 49.7% versus 38.6% (P < .05). CONCLUSION: The presence of a hernia sac in CDH is associated with better outcome, especially survival at 6 months. If the presence of a hernia sac is recognized as a particular entity, which carries a good prognosis, it is necessary to be able to diagnose it prenatally, especially in the era of prenatal fetal surgery.
Assuntos
Hérnias Diafragmáticas Congênitas/mortalidade , Hérnias Diafragmáticas Congênitas/patologia , Feminino , França , Idade Gestacional , Cabeça/diagnóstico por imagem , Cabeça/embriologia , Hérnias Diafragmáticas Congênitas/cirurgia , Humanos , Recém-Nascido , Pulmão/diagnóstico por imagem , Pulmão/embriologia , Gravidez , Prognóstico , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
INTRODUCTION AND OBJECTIVES: Different echographic and fetal magnetic resonance (MRI) measurements have been described in the diagnosis of associated malformations and the prognosis of congenital diaphragmatic hernia (CDH). We have reviewed our experience searching for useful isolated or combined parameters and how MRI can complement ultrasound. MATERIAL AND METHODS: We evaluated 29 fetuses with CDH. We examined ultrasonography: Lung to Head (LHR o/e) and in MRI: ipsilateral lung volume (IPV) and total expressed as percentage of observed / expected lung volume (VPT o/e) and percentage of herniated liver (PHH). We studied: survival, ECMO and associated malformations. RESULTS: LHR o/e was the measure that best predicted survival (p< 0.05). VPT o/e did not predict survival or the need of ECMO (p> 0.05). PHH ≥19% was related to the need of ECMO. IPV < 2 cc required ECMO more frequently (p< 0.018) and when it was 0 cc in all cases. No combination of MR measurements was superior to LHR o/e in prediction of survival. MRI complemented the ultrasound in 4 cases: diaphragmatic eventration diagnosed with HDC, right HDC with fluid in the sac that suggested thoracic cyst, differentiation between spleen and lung that measured together overestimated the LHR and/or suspicion of Cornelia de Lange due to facial malformations. CONCLUSIONS: Not a single or combined MRI measurement exceeds LHR o/e in survival prediction. MRI is related to prognosis and can be used to support ultrasound in making decisions. MRI occasionally provides complementary morphological information.
INTRODUCCION Y OBJETIVOS: Distintas medidas ecográficas y de resonancia magnética fetal (RM) han sido descritas en el diagnóstico de malformaciones asociadas y el pronóstico de la hernia diafragmática congénita (HDC). Hemos revisado nuestra experiencia buscando parámetros aislados o combinados útiles y cómo la RM puede complementar a la ecografía. MATERIAL Y METODOS: Evaluamos 29 fetos con HDC. Revisamos en ecografía: Lung to Head Ratio observado/esperado (LHR o/e) y en RM: volumen pulmonar ipsilateral (VPI) y total expresado como porcentaje del volumen pulmonar observado/esperado (VPT o/e) y porcentaje de hígado herniado (PHH). Estudiamos: supervivencia, oxigenación con membrana extracorpórea (ECMO) y malformaciones asociadas. RESULTADOS: El LHR o/e fue la medida que mejor predijo supervivencia (p< 0,05). El VPT o/e no predijo supervivencia ni la necesidad de ECMO (p> 0,05). El PHH ≥19% se relacionó con necesidad de ECMO. El VPI menor de 2 cc requirió ECMO más frecuentemente (p< 0,018) y cuando fue de 0 cc en todos los casos. Ninguna combinación de medidas de RM fue superior al LHR o/e en predicción de supervivencia. La RM complementó a la ecografía en 4 casos: eventración diafragmática diagnosticada como HDC, HDC derecha con líquido en el saco que sugería quiste torácico, diferenciación entre bazo y pulmón que medidos juntos sobreestimaba el LHR o/e y sospecha de síndrome de Cornelia de Lange por malformaciones faciales. CONCLUSIONES: Ninguna medida aislada o combinada de RM supera al LHR o/e en la predicción de supervivencia. La RM se relaciona con el pronóstico y puede usarse como apoyo de la ecografía en la toma de decisiones. La RM aporta ocasionalmente información morfológica complementaria.
Assuntos
Doenças Fetais/diagnóstico por imagem , Hérnias Diafragmáticas Congênitas/diagnóstico por imagem , Imageamento por Ressonância Magnética/métodos , Oxigenação por Membrana Extracorpórea/métodos , Feminino , Cabeça/embriologia , Humanos , Pulmão/embriologia , Medidas de Volume Pulmonar/métodos , Gravidez , Prognóstico , Estudos Retrospectivos , Ultrassonografia Pré-NatalRESUMO
BACKGROUND: To evaluate possible predictive factors of spontaneous prematurity in fetuses with congenital diaphragmatic hernia (CDH). METHODS: A retrospective cohort study was performed. Inclusion criteria were presence of CDH; absence of fetoscopy; absence of karyotype abnormality; maximum of one major malformation associated with diaphragmatic hernia; ultrasound monitoring at the Obstetrics Clinic of Clinicas Hospital at the University of São Paulo School of Medicine, from January 2001 to October 2014. The data were obtained through the electronic records and ultrasound system of our fetal medicine service. The following variables were analyzed: maternal age, primiparity, associated maternal diseases, smoking, previous spontaneous preterm birth, fetal malformation associated with hernia, polyhydramnios, fetal growth restriction, presence of intrathoracic liver, invasive procedures performed, side of hernia and observed-to- expected lung to head ratio (o/e LHR). On individual analysis, variables were assessed using the Chi-square test and the Mann-Whitney test. A multiple logistic regression model was applied to select variables independently influencing the prediction of preterm delivery. A ROC curve was constructed with the significant variable, identifying the values with best sensitivity and specificity to be suggested for use in clinical practice. RESULTS: Eighty fetuses were evaluated, of which, 21 (26.25%) were premature. O/e LHR was the only factor associated with prematurity (p = 0.020). The ROC curve showed 93% sensitivity with 48.4% specificity for the cutoff of 40%. CONCLUSION: O/e LHR was the only predictor of prematurity in this sample.
Assuntos
Hérnias Diafragmáticas Congênitas/complicações , Nascimento Prematuro/etiologia , Distribuição de Qui-Quadrado , Feminino , Feto/diagnóstico por imagem , Feto/patologia , Cabeça/diagnóstico por imagem , Cabeça/embriologia , Cabeça/patologia , Hérnias Diafragmáticas Congênitas/embriologia , Hérnias Diafragmáticas Congênitas/patologia , Humanos , Recém-Nascido , Pulmão/diagnóstico por imagem , Pulmão/embriologia , Pulmão/patologia , Tamanho do Órgão , Gravidez , Nascimento Prematuro/patologia , Curva ROC , Estudos Retrospectivos , Sensibilidade e Especificidade , Estatísticas não Paramétricas , Ultrassonografia Pré-NatalRESUMO
Drosophila melanogaster head development represents a valuable process to study the developmental control of various organs, such as the antennae, the dorsal ocelli and the compound eyes from a common precursor, the eye-antennal imaginal disc. While the gene regulatory network underlying compound eye development has been extensively studied, the key transcription factors regulating the formation of other head structures from the same imaginal disc are largely unknown. We obtained the developmental transcriptome of the eye-antennal discs covering late patterning processes at the late 2nd larval instar stage to the onset and progression of differentiation at the end of larval development. We revealed the expression profiles of all genes expressed during eye-antennal disc development and we determined temporally co-expressed genes by hierarchical clustering. Since co-expressed genes may be regulated by common transcriptional regulators, we combined our transcriptome dataset with publicly available ChIP-seq data to identify central transcription factors that co-regulate genes during head development. Besides the identification of already known and well-described transcription factors, we show that the transcription factor Hunchback (Hb) regulates a significant number of genes that are expressed during late differentiation stages. We confirm that hb is expressed in two polyploid subperineurial glia cells (carpet cells) and a thorough functional analysis shows that loss of Hb function results in a loss of carpet cells in the eye-antennal disc. Additionally, we provide for the first time functional data indicating that carpet cells are an integral part of the blood-brain barrier. Eventually, we combined our expression data with a de novo Hb motif search to reveal stage specific putative target genes of which we find a significant number indeed expressed in carpet cells.
Assuntos
Barreira Hematoencefálica/fisiologia , Proteínas de Ligação a DNA/fisiologia , Proteínas de Drosophila/fisiologia , Drosophila melanogaster/embriologia , Drosophila melanogaster/genética , Cabeça/embriologia , Neuroglia/metabolismo , Retina/embriologia , Fatores de Transcrição/fisiologia , Animais , Animais Geneticamente Modificados , Barreira Hematoencefálica/embriologia , Barreira Hematoencefálica/metabolismo , Diferenciação Celular/genética , Proteínas de Ligação a DNA/genética , Proteínas de Drosophila/genética , Embrião não Mamífero , Perfilação da Expressão Gênica , Regulação da Expressão Gênica no Desenvolvimento , Neuroglia/fisiologia , Organogênese/genética , Retina/citologia , Retina/metabolismo , Fatores de Transcrição/genéticaRESUMO
Objective: To establish a fetal biparietal diameter (BPD)-gestational age formula based on the data of pregnant women from Xiaoshan District of Hangzhou, and to evaluate its application in prenatal screening. Methods: Data of 3500 pregnant women with gestational age between 15 weeks and 19 weeks+6 receiving prenatal screening in Xiaoshan Hospital during May 2014 and May 2015 were collected. BPDs were used to establish a localized BPD-gestational age formula. The localized formula was used to evaluate the prenatal screening risks in 1759 pregnant women with irregular menstrual cycles or uncertain last menstrual period (LMP) in Xiaoshan District, and the results were compared with those calculated using formula in LifeCycle 4.0. Results: With localized formula, the total positive rate of Down syndrome, trisomy 18 syndrome and deformity of neural tube was decreased from 6.96% to 5.85% ( P<0.05), in which the positive rate of Down syndrome decreased ( P<0.05), that of deformity of neural tube increased ( P<0.05), and that of trisomy 18 syndrome remained the same ( P>0.05). The median MoMs of free-hCG ß and α-fetoprotein calculated using localized formula were significantly different from those calculated using the formula in LifeCycle 4.0 (all P<0.05), and the former ones were more closer to 1. For women of fetus diagnosed with the above diseases, the positive rate calculated using localized formula was almost the same as that calculated using the formula in LifeCycle 4.0. Conclusion: BPD-gestational age formula should be localized based on the statistical analysis of the local population, which will help to reduce the false positive rate, and make the results more accurate and reliable in prenatal screening.
Assuntos
Pesos e Medidas Corporais/normas , Cefalometria/estatística & dados numéricos , Cefalometria/normas , Idade Gestacional , Cabeça/embriologia , Programas de Rastreamento/métodos , Programas de Rastreamento/normas , Diagnóstico Pré-Natal/estatística & dados numéricos , Diagnóstico Pré-Natal/normas , Adulto , Gonadotropina Coriônica Humana Subunidade beta/sangue , Gonadotropina Coriônica Humana Subunidade beta/normas , Cromossomos Humanos Par 18 , Síndrome de Down/diagnóstico , Síndrome de Down/embriologia , Medidas em Epidemiologia , Feminino , Desenvolvimento Fetal , Humanos , Programas de Rastreamento/estatística & dados numéricos , Ciclo Menstrual , Defeitos do Tubo Neural/diagnóstico , Defeitos do Tubo Neural/embriologia , Gravidez , Diagnóstico Pré-Natal/métodos , Valores de Referência , Trissomia/diagnóstico , Síndrome da Trissomía do Cromossomo 18 , alfa-Fetoproteínas/análise , alfa-Fetoproteínas/normasRESUMO
BACKGROUND: Maternal smoking during pregnancy is linked to reduced birth weight but the gestation at onset of this relationship is not certain. We present a systematic review of the literature describing associations between maternal smoking during pregnancy and ultrasound measurements of fetal size, together with an accompanying meta-analysis. METHODS: Studies were selected from electronic databases (OVID, EMBASE and Google Scholar) that examined associations between maternal smoking or smoke exposure and antenatal fetal ultrasound measurements. Outcome measures were first, second or third trimester fetal measurements. RESULTS: There were 284 abstracts identified, 16 papers were included in the review and the meta-analysis included data from eight populations. Maternal smoking was associated with reduced second trimester head size (mean reduction 0.09 standard deviation (SD) [95% CI 0.01, 0.16]) and femur length (0.06 [0.01, 0.10]) and reduced third trimester head size (0.18 SD [0.13, 0.23]), femur length (0.27 SD [0.21, 0.32]) and estimated fetal weight (0.18 SD [0.11, 0.24]). Higher maternal cigarette consumption was associated with a lower z score for head size in the second (mean difference 0.09 SD [0, 0.19]) and third (0.15 SD [0.03, 0.26]) trimesters compared to lower consumption. Fetal measurements were not reduced for those whose mothers quit before or after becoming pregnant compared to mothers who had never smoked. CONCLUSIONS: Maternal smoking during pregnancy is associated with reduced fetal measurements after the first trimester, particularly reduced head size and femur length. These effects may be attenuated if mothers quit or reduce cigarette consumption during pregnancy.
Assuntos
Desenvolvimento Fetal , Retardo do Crescimento Fetal/etiologia , Fumar/efeitos adversos , Poluição por Fumaça de Tabaco/efeitos adversos , Peso ao Nascer , Feminino , Cabeça/embriologia , Humanos , Gravidez , Primeiro Trimestre da Gravidez , Segundo Trimestre da Gravidez , Terceiro Trimestre da GravidezRESUMO
Lethal multiple pterygium syndrome (LMPS) is a fatal hereditary disease associated with abnormalities such as pterygium-induced congenital contractures. Fetal hydrops is present in more than half of all patients with LMPS, and all patients with LMPS are either stillborn or die in the early neonatal period. Ultrasonography findings for the prenatal diagnosis of LMPS include the detection of cutaneous webbing at multiple joints, multiple joint contractures, absent limb movement, and increased nuchal translucency. Here, we describe a patient who was diagnosed as having LMPS due to continuous fetal head flexion, despite the absence of the usual characteristics of the condition, including pterygium at the joints. Thus, continuous fetal head flexion can be a useful marker for prenatally diagnosing LMPS.
Assuntos
Anormalidades Múltiplas/diagnóstico por imagem , Hipertermia Maligna/diagnóstico por imagem , Diagnóstico Pré-Natal , Anormalidades da Pele/diagnóstico por imagem , Anormalidades Múltiplas/patologia , Evolução Fatal , Feminino , Cabeça/diagnóstico por imagem , Cabeça/embriologia , Humanos , Recém-Nascido , Hipertermia Maligna/patologia , Anormalidades da Pele/patologia , Ultrassonografia Pré-NatalRESUMO
Abstract The aim of this study was to determine expression, not previously described, of PLUNC (palate, lung, and nasal epithelium clone) (BPI-fold containing) proteins in major and minor salivary glands from very early fetal tissue to the end of the second trimester and thus gain further insight into the function of these proteins. Early fetal heads, and major and minor salivary glands were collected retrospectively and glands were classified according to morphodifferentiation stage. Expression of BPI-fold containing proteins was localized through immunohistochemistry. BPIFA2, the major BPI-fold containing protein in adult salivary glands, was detected only in the laryngeal pharynx; the lack of staining in salivary glands suggested salivary expression is either very late in development or is only in adult tissues. Early expression of BPIFA1 was seen in the trachea and nasal cavity with salivary gland expression only seen in late morphodifferentiation stages. BPIFB1 was seen in early neural tissue and at later stages in submandibular and sublingual glands. BPIFA1 is significantly expressed in early fetal oral tissue but BPIFB1 has extremely limited expression and the major salivary BPIF protein (BPIFA2) is not produced in fetal development. Further studies, with more sensitive techniques, will confirm the expression pattern and enable a better understanding of embryonic BPIF protein function.
Assuntos
Humanos , Fosfoproteínas/análise , Glândulas Salivares/química , Proteínas e Peptídeos Salivares/análise , Autoantígenos/análise , Glicoproteínas/análise , Proteínas/análise , Feto/química , Palato/embriologia , Palato/química , Glândulas Salivares/embriologia , Fatores de Tempo , Língua/embriologia , Língua/química , Imuno-Histoquímica , Estudos Retrospectivos , Idade Gestacional , Desenvolvimento Fetal , Epitélio/química , Cabeça/embriologia , Pescoço/embriologiaRESUMO
Head development in vertebrates proceeds through a series of elaborate patterning mechanisms and cell-cell interactions involving cephalic neural crest cells (CNCC). These cells undergo extensive migration along stereotypical paths after their separation from the dorsal margins of the neural tube and they give rise to most of the craniofacial skeleton. Here, we report that the silencing of the LKB1 tumor suppressor affects the delamination of pre-migratory CNCC from the neural primordium as well as their polarization and survival, thus resulting in severe facial and brain defects. We further show that LKB1-mediated effects on the development of CNCC involve the sequential activation of the AMP-activated protein kinase (AMPK), the Rho-dependent kinase (ROCK) and the actin-based motor protein myosin II. Collectively, these results establish that the complex morphogenetic processes governing head formation critically depends on the activation of the LKB1 signaling network in CNCC.
Assuntos
Proteínas Aviárias/fisiologia , Crista Neural/fisiologia , Proteínas Serina-Treonina Quinases/fisiologia , Proteínas Quinases Ativadas por AMP/fisiologia , Animais , Proteínas Aviárias/antagonistas & inibidores , Proteínas Aviárias/genética , Embrião de Galinha , Anormalidades Craniofaciais/embriologia , Anormalidades Craniofaciais/genética , Regulação da Expressão Gênica no Desenvolvimento , Inativação Gênica , Cabeça/embriologia , Camundongos , Camundongos Knockout , Cadeias Leves de Miosina/fisiologia , Crista Neural/citologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Serina-Treonina Quinases/deficiência , Proteínas Serina-Treonina Quinases/genética , Transdução de Sinais/genética , Transdução de Sinais/fisiologia , Quinases Associadas a rho/fisiologiaRESUMO
BACKGROUND: Hematopoietic stem and progenitor cells (HSPCs) are generated de novo in the embryo in a process termed the endothelial to hematopoietic transition (EHT). EHT is most extensively studied in the yolk sac and dorsal aorta. Recently new sites of hematopoiesis have been described, including the heart, somites, head, and venous plexus of the yolk sac. RESULTS: We examined sites of HSPC formation in well-studied and in less well-known sites by mapping the expression of the key EHT factor Runx1 along with several other markers by means of confocal microscopy. We identified sites of HSPC formation in the head, heart and somites. We also identified sites of HSPC formation in both the arterial and venous plexuses of the yolk sac, and show that progenitors with lymphoid potential are enriched in hematopoietic clusters in close proximity to arteries. Furthermore, we demonstrate that many of the cells in hematopoietic clusters resemble monocytes or granulocytes based on nuclear shape. CONCLUSIONS: We identified sites of HSPC formation in the head, heart, and somites, confirming that embryonic hematopoiesis is less spatially restricted than previously thought. Furthermore, we show that HSPCs in the yolk sac with lymphoid potential are located in closer proximity to arteries than to veins. Developmental Dynamics 245:1011-1028, 2016. © 2016 Wiley Periodicals, Inc.
Assuntos
Células-Tronco Hematopoéticas/citologia , Animais , Artérias/embriologia , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Desenvolvimento Embrionário/genética , Desenvolvimento Embrionário/fisiologia , Feminino , Citometria de Fluxo , Cabeça/embriologia , Coração/embriologia , Células-Tronco Hematopoéticas/metabolismo , Camundongos , Microscopia Confocal , Somitos/embriologia , Saco Vitelino/embriologiaRESUMO
PURPOSE: Congenital diaphragmatic hernia (CDH) is associated with high postnatal mortality because of pulmonary hypoplasia. The prognostic utility of serial lung-to-head circumference measurements as a marker of lung growth has not been described. Our objective was to examine the relationship between the rate of interval increase of LHR and postnatal survival in left-sided CDH. METHODS: We retrospectively reviewed charts of all left-sided CDH patients from January 2004 to July 2014. All ultrasound studies performed at our institution (n=473) were reviewed. Categorical and continuous data were analyzed by chi-square and Mann-Whitney t-test, respectively, and slope analysis was performed by linear regression analysis (p<0.05). RESULTS: A total of 226 patients were studied, with 154 long-term survivors and 72 non-survivors. Established markers of CDH severity, including intrathoracic liver position and requirement for patch repair, were significantly increased in non-survivors (p<0.0001). The rate of LHR increase as measured by linear regression and slope analysis was significantly increased in long-term survivors (p=0.0175). CONCLUSIONS: Our findings indicate that the interval increase in LHR levels over the course of gestation correlate with survival in left-sided CDH patients. Regular ultrasonographic re-evaluation of LHR throughout gestation following diagnosis of CDH may provide prognostic insight and help guide patient management.