RESUMEN

Gap closure is a common morphogenetic process. In mammals, failure to close the embryonic hindbrain neuropore (HNP) gap causes fatal anencephaly. We observed that surface ectoderm cells surrounding the mouse HNP assemble high-tension actomyosin purse strings at their leading edge and establish the initial contacts across the embryonic midline. Fibronectin and laminin are present, and tensin 1 accumulates in focal adhesion-like puncta at this leading edge. The HNP gap closes asymmetrically, faster from its rostral than caudal end, while maintaining an elongated aspect ratio. Cell-based physical modeling identifies two closure mechanisms sufficient to account for tissue-level HNP closure dynamics: purse-string contraction and directional cell motion implemented through active crawling. Combining both closure mechanisms hastens gap closure and produces a constant rate of gap shortening. Purse-string contraction reduces, whereas crawling increases gap aspect ratio, and their combination maintains it. Closure rate asymmetry can be explained by asymmetric embryo tissue geometry, namely a narrower rostral gap apex, whereas biomechanical tension inferred from laser ablation is equivalent at the gaps' rostral and caudal closure points. At the cellular level, the physical model predicts rearrangements of cells at the HNP rostral and caudal extremes as the gap shortens. These behaviors are reproducibly live imaged in mouse embryos. Thus, mammalian embryos coordinate cellular- and tissue-level mechanics to achieve this critical gap closure event.

Asunto(s)

Embrión de Mamíferos/metabolismo , Cresta Neural/metabolismo , Tubo Neural/metabolismo , Rombencéfalo/metabolismo , Anencefalia/embriología , Anencefalia/genética , Anencefalia/metabolismo , Animales , Cadherinas/metabolismo , Embrión de Mamíferos/embriología , Femenino , Fibronectinas/metabolismo , Laminina/metabolismo , Masculino , Ratones Endogámicos C57BL , Ratones Noqueados , Ratones Transgénicos , Microscopía Confocal/métodos , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Cresta Neural/embriología , Tubo Neural/embriología , Rombencéfalo/embriología , Imagen de Lapso de Tiempo/métodos

RESUMEN

BACKGROUND: To compare the growth of the prostate in anencephalic, prune belly syndrome (PBS) and control fetuses. METHODS: We studied 35 prostates from normal human fetuses aged 11-22 weeks postconception (WPC); 15 from anencephalic fetuses aged 13-19 WPC; and 6 from PBS fetuses aged 13-31WPC. After prostate dissection, we evaluated the prostate length, width and thickness with the aid of a computer program (Image Pro and Image J). The fetal prostate volume (PV) was calculated using the ellipsoid formula: PV = [length × thickness × width] × 0.523. The prostates were dissected and the PV was measured with the aid of the same computer program. Means were statistically compared using the unpaired t-test and linear regression was performed. RESULTS: In 2 PBS fetuses we observed prostatic atresia. We did not observe significant differences in PV when comparing the control group (PV: 6.1 to 313.81 mm, mean = 70.85 mm: SD = 71.43 mm) with anencephalic fetuses: p = 0.3575 (PV: 5.1 to 159.11 mm, mean = 42.94 mm; SD = 40.11 mm) and PBS fetuses: p > 0.999 (PV: 10.89 to 148.71 mm, mean = 55.4 mm; SD = 63.64 mm). The linear regression analysis indicated that the PV in the control group (r2 = 0.3096; p = 0.0004), anencephalic group (r2 = 0.3778; p = 0.0148) and PBS group (r2 = 0.9821; p < 0.009) increased significantly and positively with fetal age (p < 0.0001). CONCLUSIONS: We did not observe significant differences in development of the prostate in fetuses with anencephaly and in 2/3 of fetuses with PBS during the fetal period studied. In 1/3 of the PBS fetuses, the prostate had important atresia. LEVEL OF EVIDENCE: Level III.

Asunto(s)

Anencefalia/embriología , Próstata/embriología , Próstata/crecimiento & desarrollo , Síndrome del Abdomen en Ciruela Pasa/embriología , Feto/embriología , Edad Gestacional , Humanos , Masculino , Tamaño de los Órganos

RESUMEN

A previously unrecognized first-trimester presentation of the acrania-anencephaly sequence is described. Ultrasound features included a constriction ring around the external base of the developing skull and an enlarged globular head, resembling a Turkish turban, with large cystic spaces replacing the brain. This constellation of findings was noted in 3 first-trimester fetuses. In 2 of them, it was possible to identify the amniotic membrane attached to the constriction ring. One case presented with anencephaly and fetal demise at 16 weeks. The other 2 women terminated the pregnancies and aborted anencephalic fetuses. This subtype of the acrania-anencephaly sequence could represent an earlier segmental rupture of the amnion, which subsequently entraps the developing fetal skull.

Asunto(s)

Anencefalia/diagnóstico por imagen , Anencefalia/embriología , Primer Trimestre del Embarazo , Ultrasonografía Prenatal/métodos , Aborto Eugénico , Encéfalo/diagnóstico por imagen , Encéfalo/embriología , Resultado Fatal , Femenino , Humanos , Embarazo , Cráneo/diagnóstico por imagen , Cráneo/embriología

RESUMEN

Exencephaly/anencephaly is one of the leading causes of neonatal mortality and the most extreme open neural tube defect with no current treatments and limited mechanistic understanding. We hypothesized that exencephaly leads to a local neurodegenerative process in the brain exposed to the amniotic fluid as well as diffuse degeneration in other encephalic areas and the spinal cord. To evaluate the consequences of in utero neural tissue exposure, brain and spinal cord samples from E17 exencephalic murine fetuses (maternal intraperitoneal administration of valproic acid at E8) were analyzed and compared to controls and saline-injected shams (n = 11/group). Expression of apoptosis and senescence genes (p53, p21, p16, Rbl2, Casp3, Casp9) was determined by qRT-PCR and protein expression analyzed by western blot. Apoptosis was measured by TUNEL assay and PI/AV flow cytometry. Valproic acid at E8 induced exencephaly in 22% of fetuses. At E17 the fetuses exhibited the characteristic absence of cranial bones. The brain structures from exencephalic fetuses demonstrated a loss of layers in cortical regions and a complete loss of structural organization in the olfactory bulb, hippocampus, dental gyrus and septal cortex. E17 fetuses had reduced expression of NeuN, GFAP and Oligodendrocytes in the brain with primed microglia. Intrinsic apoptotic activation (p53, Caspase9 and 3) was upregulated and active Caspase3 localized to the layer of brain exposed to the amniotic fluid. Senescence via p21-Rbl2 was increased in the brain and in the spinal cord at the lamina I-II of the somatosensory dorsal horn. The current study characterizes CNS alterations in murine exencephaly and demonstrates that degeneration due to intrinsic apoptosis and senescence occurs in the directly exposed brain but also remotely in the spinal cord.

Asunto(s)

Anencefalia/patología , Apoptosis , Encéfalo/patología , Necrosis/patología , Defectos del Tubo Neural/patología , Médula Espinal/patología , Líquido Amniótico/metabolismo , Anencefalia/inducido químicamente , Anencefalia/embriología , Animales , Apoptosis/efectos de los fármacos , Apoptosis/genética , Encéfalo/citología , Encéfalo/embriología , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Senescencia Celular/efectos de los fármacos , Senescencia Celular/genética , Inhibidor p16 de la Quinasa Dependiente de Ciclina/metabolismo , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/genética , Inhibidor p21 de las Quinasas Dependientes de la Ciclina/metabolismo , Modelos Animales de Enfermedad , Progresión de la Enfermedad , Femenino , Ratones , Microglía/citología , Microglía/efectos de los fármacos , Microglía/metabolismo , Microglía/patología , Necrosis/embriología , Necrosis/metabolismo , Neuronas/citología , Neuronas/patología , Proteína p130 Similar a la del Retinoblastoma/genética , Proteína p130 Similar a la del Retinoblastoma/metabolismo , Médula Espinal/citología , Médula Espinal/embriología , Médula Espinal/metabolismo , Proteína p53 Supresora de Tumor/metabolismo , Regulación hacia Arriba , Ácido Valproico

RESUMEN

BACKGROUND: Neural tube defects (NTDs) are among the most common and severe congenital malformations of the central nervous system. Animal studies have shown that apoptosis is involved in the development of NTDs. However, little evidence is available from human studies. We aim to examine the level of apoptosis and expression of apoptosis-regulating proteins of human terminated fetuses. METHODS: A total of 37 NTD cases and 21 controls from pregnancy terminations were recruited. Tissues of the central nervous system were obtained through autopsy. Apoptosis of neuroepithelial cells was examined by terminal deoxynucleotidyl transferase-mediated deoxyuridinetriphosphate nick end-labeling (TUNEL) assay. Expression of PAX3, p53, and caspase 3/8/9 in central nervous tissue was measured using Western blotting. RESULTS: More TUNEL-positive apoptosis cells were observed in the central nervous tissue of NTD cases than those of controls (p < 0.05). In spinal cord tissue, lower PAX3 expression, higher p53 expression, and increased levels of cleaved caspase 3(17kD) and cleaved caspase 8 (18kD) were found in anencephaly cases but not in spina bifida cases when compared with controls. In brain tissue, levels of PAX3 were significantly reduced in both encephalocele and spina bifida subtypes; the expression levels of cleaved caspase 3(17 kD) of encephalocele cases and cleaved caspase 8(47/45 kD) in spina bifida cases were higher than in controls; no difference was found in the expression of p53 or caspase 9 between NTDs and controls. CONCLUSION: These findings provide some evidence that excessive apoptosis in fetal central nervous tissues may be associated with the development of human NTDs. Birth Defects Research 109:1596-1604, 2017. © 2017 Wiley Periodicals, Inc.

Asunto(s)

Apoptosis/fisiología , Caspasas/metabolismo , Defectos del Tubo Neural/fisiopatología , Factor de Transcripción PAX3/biosíntesis , Proteína p53 Supresora de Tumor/biosíntesis , Feto Abortado/patología , Aborto Inducido , Anencefalia/embriología , Animales , Estudios de Casos y Controles , Caspasas/análisis , Femenino , Humanos , Etiquetado Corte-Fin in Situ , Lactante , Recién Nacido , Masculino , Ratones , Tubo Neural/metabolismo , Tubo Neural/fisiología , Defectos del Tubo Neural/genética , Defectos del Tubo Neural/metabolismo , Factor de Transcripción PAX3/genética , Factor de Transcripción PAX3/metabolismo , Embarazo , Atención Prenatal , Diagnóstico Prenatal , Médula Espinal/patología , Disrafia Espinal/embriología , Proteína p53 Supresora de Tumor/genética , Proteína p53 Supresora de Tumor/metabolismo

RESUMEN

OBJECTIVE: We present molecular cytogenetic characterization of a duplication of 15q24.2-q26.2 associated with anencephaly and neural tube defect (NTD). CASE REPORT: A 35-year-old pregnant woman was found to have a fetus with anencephaly by prenatal ultrasound at 12 weeks of gestation. The pregnancy was subsequently terminated, and a malformed fetus was delivered with anencephaly. Cytogenetic analysis of the cultured placental tissues revealed a karyotype of 46,XX,dup(15) (q24.2q26.2). Parental karyotypes were normal. Array comparative genomic hybridization analysis of the placental tissues revealed a 20.36-Mb duplication of 15q24.2-q26.2 encompassing 100 Online Mendelian Inheritance of in Man (OMIM) genes including LINGO1, MTHFS, KIF7 and CHD2. Metaphase fluorescence in situ hybridization analysis using 15q25.1-specidic probe confirmed a duplication of 15q25.1. Polymorphic DNA marker analysis showed a maternal origin of the duplication. CONCLUSION: A duplication of chromosome 15q24.2-q26.2 can be associated with NTD.

Asunto(s)

Anencefalia/genética , Defectos del Tubo Neural/genética , Trisomía/genética , Aborto Inducido , Adulto , Anencefalia/embriología , Cromosomas Humanos Par 15/genética , Hibridación Genómica Comparativa , Análisis Citogenético , Femenino , Humanos , Hibridación Fluorescente in Situ , Cariotipo , Cariotipificación , Defectos del Tubo Neural/embriología , Embarazo , Ultrasonografía Prenatal

RESUMEN

Lipopolysaccharide (LPS) has been associated with adverse pregnant outcomes, including fetal demise, intra-uterine growth restriction (IUGR), neural tube defects (NTDs) and preterm delivery in rodent animals. Previous studies demonstrated that melatonin protected against LPS-induced fetal demise, IUGR and preterm delivery. The aim of the present study was to investigate the effects of melatonin on LPS-induced NTDs. All pregnant mice except controls were intraperitoneally injected with LPS (25 µg/kg) daily from gestational day (GD)8 to GD12. Some pregnant mice were orally administered with melatonin (MT, 50 mg/kg) before each LPS injection. A five-day LPS injection resulted in 27.5% of fetuses with anencephaly, exencephaly or encephalomeningocele. Additional experiment showed that maternal LPS exposure significantly down-regulated placental proton-coupled folate transporter (pcft) and disturbed folate transport from maternal circulation through the placentas into the fetus. Interestingly, melatonin significantly attenuated LPS-induced down-regulation of placental pcft. Moreover, melatonin markedly improved the transport of folate from maternal circulation through the placentas into the fetus. Correspondingly, orally administered melatonin reduced the incidence of LPS-induced anencephaly, exencephaly or encephalomeningocele. Taken together, these results suggest that orally administered melatonin prevents LPS-induced NTDs through alleviating LPS-induced disturbance of folate transport from maternal circulation through the placenta into the fetus.

Asunto(s)

Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Melatonina/farmacología , Defectos del Tubo Neural/prevención & control , Placenta/metabolismo , Administración Oral , Anencefalia/inducido químicamente , Anencefalia/embriología , Anencefalia/prevención & control , Animales , Antioxidantes/administración & dosificación , Antioxidantes/farmacología , Quimiocinas/genética , Quimiocinas/metabolismo , Femenino , Ácido Fólico/sangre , Ácido Fólico/metabolismo , Mediadores de Inflamación/metabolismo , Lipopolisacáridos , Masculino , Intercambio Materno-Fetal/efectos de los fármacos , Melatonina/administración & dosificación , Meningocele/inducido químicamente , Meningocele/embriología , Meningocele/prevención & control , Ratones Endogámicos ICR , Defectos del Tubo Neural/inducido químicamente , Defectos del Tubo Neural/embriología , Embarazo , Transportador de Folato Acoplado a Protón/genética , Transportador de Folato Acoplado a Protón/metabolismo , Reacción en Cadena de la Polimerasa de Transcriptasa Inversa

RESUMEN

BACKGROUND: Genetic variations affecting neural tube closure along the head result in malformations to the face and brain, posing a significant impact on health care costs and the quality of life. METHODS: We have established a mouse line from a mutation that arose spontaneously in our wild-type colony that we called tuft. Tuft mice have heritable midline craniofacial defects featuring an anterior lipomatous cephalocele. RESULTS: Whole-mount skeletal stains indicated that affected newborns had a broader interfrontal suture where the cephalocele emerged between the frontal bones. Mice with a cephalocele positioned near the rostrum also presented craniofacial malformations such as ocular hypertelorism and midfacial cleft of the nose. Gross and histological examination revealed that the lipomatous cephalocele originated as a fluid filled cyst no earlier than E14.5 while embryos with a midfacial cleft was evident during craniofacial development at E11.5. Histological sections of embryos with a midfacial cleft revealed the cephalic neuroectoderm remained proximal or fused to the frontonasal ectoderm about the closure site of the anterior neuropore, indicating a defect to neural tube closure. We found the neural folds along the rostrum of E9 to E10.5 embryos curled inward and failed to close as well as embryos with exencephaly and anencephaly at later stages. Whole-mount in situ hybridization of anterior markers Fgf8 and Sonic hedgehog indicated closure of the rostral site was compromised in severe cases. CONCLUSION: We present a model demonstrating how anterior cranial cephaloceles are generated following a defect to neural tube closure and relevance to subsequent craniofacial morphogenesis in the tuft mouse.

Asunto(s)

Anomalías Craneofaciales/embriología , Encefalocele/embriología , Huesos Faciales/embriología , Tubo Neural/embriología , Anencefalia/embriología , Animales , Desarrollo Óseo/genética , Modelos Animales de Enfermedad , Huesos Faciales/anomalías , Factor 8 de Crecimiento de Fibroblastos/genética , Proteínas Hedgehog/genética , Ratones

Asunto(s)

Anomalías Múltiples/diagnóstico por imagen , Anomalías Múltiples/embriología , Anencefalia/diagnóstico por imagen , Anencefalia/embriología , Gemelos Siameses , Ultrasonografía Prenatal/métodos , Adulto , Femenino , Humanos , Embarazo

RESUMEN

The aim of this study is to test the glomerular and other quantitative parameters of kidneys of anencephalic fetuses and comparing those to "normal" fetuses. In this study, 20 kidneys of human fetuses (5 boys and 5 girls of anencephalic fetus, and 5 boys and 5 girls of normal fetus), at gestational ages of 25-30 weeks, were examined. This study is based on two basic research methods: one is a conventional anatomical measurement at the macroscopical level; the other is a design-biased stereological method at the microscopical level. Physical dissector and Cavalieri principle were used to estimate the total and numerical density of glomerulus and the volume of kidney, respectively. The results of the two types of investigation were compared based on anencephalic/normal and boy/girl kidneys at both the macroscopical and microscopical levels. There was no significant difference found between the quantitative features of kidneys (volume of kidneys and mean number and/or height of glomerulus) belonging to anencephalic and normal fetuses. The results of this study suggest that anencephalic fetuses did not differ from normal fetuses in respect of kidneys.

Asunto(s)

Anencefalia/embriología , Enfermedades Fetales , Feto/embriología , Riñón/embriología , Femenino , Estudios de Seguimiento , Edad Gestacional , Humanos , Masculino , Proyectos Piloto , Embarazo , Estudios Retrospectivos

RESUMEN

The development of the embryonic brain critically depends on successfully completing cranial neural tube closure (NTC). Failure to properly close the neural tube results in significant and potentially lethal neural tube defects (NTDs). We believe these malformations are caused by disruptions in normal developmental programs such as those involved in neural plate morphogenesis and patterning, tissue fusion, and coordinated cell behaviors. Cranial NTDs include anencephaly and craniorachischisis, both lethal human birth defects. Newly emerging methods for molecular and cellular analysis offer a deeper understanding of not only the developmental NTC program itself but also mechanical and kinetic aspects of closure that may contribute to cranial NTDs. Clarifying the underlying mechanisms involved in NTC and how they relate to the onset of specific NTDs in various experimental models may help us develop novel intervention strategies to prevent NTDs.

Asunto(s)

Encéfalo/embriología , Tubo Neural/embriología , Anencefalia/embriología , Animales , Humanos , Mutación , Defectos del Tubo Neural

RESUMEN

Partitioning defective 3 homolog (PARD3) is an attractive candidate gene for screening neural tube defect (NTD) risk. To investigate the role of genetic variants in PARD3 on NTD risk, a case-control study was performed in a region of China with a high prevalence of NTDs. Total 53 single-nucleotide polymorphisms (SNPs) in PARD3 were genotyped in 224 fetuses with NTDs and in 253 normal fetuses. We found that 6 SNPs (rs2496720, rs2252655, rs3851068, rs118153230, rs10827337, and rs12218196) were statistically associated with NTDs (P < .05). After stratifying participants by NTD phenotypes, the significant association only existed in cases with anencephaly rather than spina bifida. Further haplotype analysis confirmed the association between PARD3 polymorphisms and NTD risk (global test P = 3.41e-008). Our results suggested that genetic variants in PARD3 were associated with susceptibility to NTDs in a Chinese Han population, and this association was affected by NTD phenotypes.

Asunto(s)

Proteínas de Ciclo Celular/genética , Proteínas de la Membrana/genética , Defectos del Tubo Neural/genética , Polimorfismo de Nucleótido Simple , Proteínas Adaptadoras Transductoras de Señales , Anencefalia/diagnóstico por imagen , Anencefalia/embriología , Anencefalia/genética , Anencefalia/metabolismo , Estudios de Casos y Controles , Proteínas de Ciclo Celular/metabolismo , China , Femenino , Estudios de Asociación Genética , Humanos , Proteínas de la Membrana/metabolismo , Defectos del Tubo Neural/diagnóstico por imagen , Defectos del Tubo Neural/embriología , Defectos del Tubo Neural/metabolismo , Embarazo , Médula Espinal/embriología , Médula Espinal/metabolismo , Ultrasonografía Prenatal

RESUMEN

The frequency of fetal arcadia in the world is 1:35,000 to 1:48,000 pregnancies; is currently estimated that 1% of newborns in developed countries are the result of assisted reproduction techniques and the frequency of twin pregnancies is close to 18%, of these, an estimated relative risk for cardiac defect is 1.6. However, the association of acardiac fetus, twin pregnancy and assisted reproductive techniques is not fully established. In this paper, we describe a case of fetal acardia, in a pregnancy resulting from assisted reproduction and its obstetric care.

Asunto(s)

Enfermedades en Gemelos , Fertilización In Vitro , Muerte Fetal/etiología , Corazón Fetal/anomalías , Embarazo Múltiple , Anomalías Múltiples/embriología , Adulto , Anencefalia/embriología , Cesárea , Transferencia de Embrión , Femenino , Muerte Fetal/diagnóstico por imagen , Humanos , Recién Nacido , Masculino , Embarazo , Riesgo , Ultrasonografía

RESUMEN

PRECIS: Many genes are differentially expressed in normal compared to anencephalic human fetal adrenals (HFAs), especially the Fras-1-related extracellular matrix protein (FREM2) gene. FREM2 expression appears to be regulated by adrenocorticotrophic hormone (ACTH). CONTEXT: The expression profiles of genes responsible for cortical growth and zonation in the HFA gland are poorly characterized. The neural tube disorder anencephaly is associated with fetal adrenal hypoplasia with a large size reduction of the fetal zone of the HFA. OBJECTIVE: To determine gene expression profile differences in the adrenals of anencephalic compared to normal HFAs to identify genes that may play important roles in adrenal development. DESIGN AND METHODS: Fresh tissues were obtained at the time of autopsy from normal and anencephalic human fetuses delivered at mid-gestation. The following techniques were used: cell culture, messenger RNA (mRNA) extraction, microarray analysis, complementary DNA (cDNA) synthesis, quantitative real-time reverse transcriptase polymerase chain reaction (QT-PCR). RESULTS: We identified over 40 genes expressed at levels 4-fold or greater in the normal versus anencephalic HFAs and that 28 genes were expressed at increased levels in the anencephalic HFA. The expression of FREM2 at approximately 40-fold greater levels in the normal HFA compared to the HFA of anencephalic fetuses was confirmed by QT-PCR. Expression of FREM2 in the kidney was not significantly different between normal and anencephalic fetuses. In cultured HFA cells, ACTH treatment for 48 hours increased the expression of FREM2 and a gene responsive to ACTH, CYP17, but not tyrosine hydroxylase. CONCLUSIONS: Abnormal expression of many genes may be involved in the adrenal hypoplasia seen in anencephaly. FREM2 appears to be regulated by ACTH and is the most differentially expressed gene, which may be important in the development and function of the HFA, particularly the fetal zone of the HFA.

Asunto(s)

Glándulas Suprarrenales/embriología , Anencefalia/embriología , Anencefalia/metabolismo , Proteínas de la Matriz Extracelular/genética , Regulación del Desarrollo de la Expresión Génica , Glándulas Suprarrenales/metabolismo , Hormona Adrenocorticotrópica/farmacología , Células Cultivadas , Proteínas de la Matriz Extracelular/fisiología , Femenino , Regulación del Desarrollo de la Expresión Génica/efectos de los fármacos , Edad Gestacional , Humanos , Embarazo , ARN Mensajero/análisis

RESUMEN

This study was to investigate the effect of the absence of ganglion cells on the development of human retinal vasculature. Anencephaly (AnC) and age-matched control eyes derived from each three spontaneously aborted fetus (ranging from 15 to 20 weeks gestation) were subjected to immunofluorescence staining for HIF-1alpha, Thy-1, glial fibrillary acidic protein (GFAP) and platelet/endothelial cell adhesion molecule (PECAM) and apoptosis assay. In developing mouse retina, Western blotting for hypoxia-inducible factor-1alpha (HIF-1alpha) and vascular endothelial growth factor (VEGF) was performed. Under hypoxic condition (O(2) < 1%), cellular proliferation and VEGF mRNA expression in astrocytes were measured. Apoptotic cells in AnC retina were primarily localized in the ganglion cell layer (GCL), whereas apoptotic cells in normal retina were distributed in the retinoblastic layer. With increase of apoptotic cells in GCL of AnC retina, HIF-1alpha expression were severely distinguished in avascular retina and GFAP expression in junctional area between avascular and vascular retina was much reduced, accompanied by decrease of PECAM expression compared to normal retina. In developing mouse retina, HIF-1alpha and VEGF expression were high in hypoxic retina of early stage with incomplete vascular development and then progressively decreased with regression to arborous pattern of matured vascular networks. In hypoxic condition, a significant increase in cellular proliferation and VEGF mRNA expression was observed in astrocytes. Therefore, our results suggest that vascular attenuation in AnC retina could be closely related to the absence of ganglion cells as the metabolic demander to induce retinal vascular development.

Asunto(s)

Anencefalia/embriología , Vasos Retinianos/embriología , Anencefalia/patología , Animales , Apoptosis , Hipoxia de la Célula/fisiología , Línea Celular , Proliferación Celular , Proteína Ácida Fibrilar de la Glía/metabolismo , Humanos , Subunidad alfa del Factor 1 Inducible por Hipoxia/metabolismo , Ratones , Ratones Endogámicos C57BL , Molécula-1 de Adhesión Celular Endotelial de Plaqueta/metabolismo , Ratas , Retina/citología , Retina/patología , Antígenos Thy-1/metabolismo , Factor A de Crecimiento Endotelial Vascular/metabolismo

RESUMEN

In the study, stereological, histological, and anatomical techniques were used to investigate structural and morphometrical features of anencephalic and normal fetal kidneys. Twenty human fetal kidneys (5 male and 5 female anencephalic fetuses, and 5 male and 5 female normal fetuses) at gestational ages 30 to 35 weeks were examined. Our study used two basic research methods. One was conventional anatomical measurement at the macroscopic level, such as volume, length, weight, etc. The other consisted of conventional and modern microscopic techniques. The microscopic techniques were based on two research methods: histopathological examination at light microscopic level and stereological estimations, including mean kidney volumes, obtained by the Cavalieri method, and the total number and mean height of the glomeruli via the physical dissector method. There was no statistical difference between the two groups in terms of width, height, weight, and fluid replacement volumes. Microscopic quantitative assessment found no statistical differences either, in terms of the kidney volumes and the number and height of the glomeruli. Our findings suggest that kidneys from anencephalic infants may be a suitable alternative for renal transplantation.

Asunto(s)

Anencefalia/embriología , Feto/embriología , Trasplante de Riñón , Riñón/embriología , Morfogénesis/fisiología , Donantes de Tejidos , Anencefalia/patología , Femenino , Feto/patología , Edad Gestacional , Humanos , Riñón/patología , Glomérulos Renales/embriología , Glomérulos Renales/patología , Masculino

RESUMEN

This is the first report of an acephalous lamb from the transfer of an in vitro-produced sheep embryo. Twelve in vitro-fertilized embryos were transferred to 4 recipient ewes (3 embryos/ewe). Two ewes remained pregnant: one delivered a normal female lamb, the other a male acephalous lamb. Possible contributing factors are discussed.

Asunto(s)

Anencefalia/veterinaria , Transferencia de Embrión/veterinaria , Fertilización In Vitro/veterinaria , Resultado del Embarazo , Ovinos/fisiología , Anencefalia/embriología , Anencefalia/genética , Animales , Animales Recién Nacidos , Femenino , Masculino , Embarazo

RESUMEN

Apart from a series of 10 acephalus/acardius (Ac/Ac) cases described from a pathological point of view, and the analysis of a review of published cases, we have been unable to find any epidemiological studies on Ac/Ac. Using data from the Spanish Collaborative Study of Congenital Malformations (ECEMC), we present here what seems to be the first epidemiological analysis of a consecutive series of the Ac/Ac type of monozygotic twins (MZT). Among a total of 2,281,604 consecutive births, 11 cases of Ac/Ac MZT were detected, giving a frequency of 0.48 per 100,000 births. However, we consider the period 1980-1985 as the baseline for our data, as in this period voluntary termination of pregnancy was not possible in Spain, and the frequency of Ac/Ac MZT was 0.49 per 100,000 births. Nonetheless, this frequency should be considered as a minimal estimation. The characteristics of these Ac/Ac cases indicate that they are more frequent in males (sex ratio 2.67). In addition, gestational age in Ac/Ac cases was 2.41 and 3.12 weeks lower than in malformed and control twins, respectively. Similarly, their mothers are 4.54 and 4.68 years younger than mothers of separate malformed and control twins, respectively. To understand the biological basis behind the occurrence of MZT in the context of recent observations, we evaluate the hypothesis that the epigenetic processes involved in the early cleavage of the embryo, and in blastocyst formation during development, may be implicated in twinning.

Asunto(s)

Anomalías Múltiples/genética , Anencefalia/genética , Epigénesis Genética , Cardiopatías Congénitas/genética , Anomalías Múltiples/embriología , Anomalías Múltiples/epidemiología , Anencefalia/embriología , Anencefalia/epidemiología , Estudios de Casos y Controles , Bases de Datos Genéticas , Femenino , Cardiopatías Congénitas/embriología , Cardiopatías Congénitas/epidemiología , Humanos , Recién Nacido , Masculino , Modelos Genéticos , Embarazo , Razón de Masculinidad , España/epidemiología , Gemelos Monocigóticos

RESUMEN

This review article discusses prenatal screening and diagnosis of neural tube defects (NTD). High detection rates occur in countries operating ultrasound screening programmes because classical two-dimensional ultrasound cranial signs (lemon shaped head, banana cerebellum, ventriculomegaly) are important diagnostic clues to the presence of spina bifida. Careful evaluation of both the spine and a search for other abnormalities is warranted. Important prognostic information for spina bifida relates to the lesion level, with a "watershed" between L3 and L4 marking a very high chance of being wheelchair bound with the higher lesions. Three-dimensional ultrasound using multiplanar views can achieve diagnostic accuracy within one vertebral body in around 80% of patients. There are high rates of pregnancy termination for spina bifida in many European countries, but the use of new imagining techniques allow better prediction of outcome, and consequently a refinement of prenatal counselling.

Asunto(s)

Defectos del Tubo Neural/diagnóstico , Diagnóstico Prenatal/métodos , Anencefalia/diagnóstico por imagen , Anencefalia/embriología , Aberraciones Cromosómicas , Consejo , Encefalocele/diagnóstico por imagen , Encefalocele/embriología , Femenino , Humanos , Meningocele/diagnóstico por imagen , Meningocele/embriología , Defectos del Tubo Neural/diagnóstico por imagen , Defectos del Tubo Neural/embriología , Embarazo , Pronóstico , Disrafia Espinal/diagnóstico por imagen , Disrafia Espinal/embriología , Ultrasonografía Prenatal/métodos , alfa-Fetoproteínas/análisis

RESUMEN

La acranea es la anomalía fetal caracterizada por la ausencia de la bóveda craneana, acompañado de un completo tejido cerebral. Su causa es debida a una falla en la migración del mesenquima ectodernal o a una discrupción de las bandas amnióticas. La incidencia no es conocida, muy pocos casos han sido reportados en la literatura mundial. El diagnóstico prenatal se identifica por la ausencia de la bóveda craneana a través de la ultrasonografía. El pronóstico es fatal. Nosotros reportamos nuestra experiencia en un feto diagnosticado por ultrasonografía con acranea a las 12 semanas de edad gestacional.

Asunto(s)

Humanos , Femenino , Embarazo , Anencefalia/embriología , Anomalías Congénitas/diagnóstico , Anomalías Craneofaciales/diagnóstico , Diagnóstico Prenatal , Tubo Neural/anomalías , Ultrasonografía Prenatal/métodos , Primer Trimestre del Embarazo , Pronóstico