AIM: To study congenital heart defects (CHDs), evaluate their relation to extra-cardiac pathologies, and assess the significance of prenatal diagnostics for heart diseases. METHODS: Data from 1999-2017 were analyzed for the incidence of significant CHDs in fetuses (prenatal ultrasound/echocardiography) and children, including, where applicable, autopsy data and genetic evaluation. RESULTS: Among 220,400 fetuses, 819 (3.7 cases per 1000) significant CHDs were observed. Of the total, 53% (435/819) of CHDs were diagnosed prenatally. The heart defect was an isolated impairment in 78% (640/819), associated with a genetic impairment in 16% (128/819), and with extra-cardiac malformations without genetic pathology in 6% (51/819). Chromosomal aberrations were diagnosed prenatally in 70% (90/128) of those affected and extra-cardiac conditions in 86% (44/51). The CHD and genetic pathology association was more frequent prenatally [21% (90/435) vs. postnatally: 10% (38/384; P<0.0001)], as was the association between CHD with other extra-cardiac pathology and a normal karyotype [prenatally: 10% (44/435) vs. postnatally: 2% (7/384; P<0.0001)]. CONCLUSION: Heart defects are most frequently isolated, with genetic and other extra-cardiac anomalies in about one third of cases, significantly linked to prenatal diagnostics.
- MeSH
- chromozomální aberace embryologie MeSH
- echokardiografie MeSH
- gestační stáří MeSH
- incidence MeSH
- lidé MeSH
- novorozenec MeSH
- pitva MeSH
- prenatální diagnóza * statistika a číselné údaje MeSH
- retrospektivní studie MeSH
- těhotenství MeSH
- ultrasonografie prenatální MeSH
- vrozené srdeční vady diagnostické zobrazování embryologie mortalita MeSH
- výsledek těhotenství MeSH
- Check Tag
- lidé MeSH
- novorozenec MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- časopisecké články MeSH
Noncompaction cardiomyopathy is characterized by the presence of extensive trabeculations, which could lead to heart failure and malignant arrhythmias. How trabeculations resolve to form compact myocardium is poorly understood. Elucidation of this process is critical to understanding the pathophysiology of noncompaction disease. Here we use genetic lineage tracing to mark the Nppa+or Hey2+cardiomyocytes as trabecular and compact components of the ventricular wall. We find that Nppa+and Hey2+cardiomyocytes, respectively, from the endocardial and epicardial zones of the ventricular wall postnatally. Interposed between these two postnatal layers is a hybrid zone, which is composed of cells derived from both the Nppa+and Hey2+populations. Inhibition of the fetal Hey2+cell contribution to the hybrid zone results in persistence of excessive trabeculations in postnatal heart. Our findings indicate that the expansion of Hey2+fetal compact component, and its contribution to the hybrid myocardial zone, are essential for normal formation of the ventricular walls.Fetal trabecular muscles in the heart undergo a poorly described morphogenetic process that results into a solidified compact myocardium after birth. Tian et al. show that cardiomyocytes in the fetal compact layer also contribute to this process, forming a hybrid myocardial zone that is composed of cells derived from both trabecular and compact layers.
- MeSH
- buněčný rodokmen MeSH
- kardiomyocyty metabolismus MeSH
- kardiomyopatie vrozené embryologie metabolismus MeSH
- myokard metabolismus patologie MeSH
- myši MeSH
- natriuretický peptid typu C metabolismus MeSH
- novorozená zvířata MeSH
- organogeneze MeSH
- proteinové prekurzory metabolismus MeSH
- represorové proteiny metabolismus MeSH
- srdce embryologie růst a vývoj MeSH
- srdeční komory embryologie růst a vývoj metabolismus patologie MeSH
- transkripční faktory bHLH metabolismus MeSH
- vrozené srdeční vady embryologie metabolismus MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
BACKGROUND: TALE-class homeodomain transcription factors Meis and Pbx play important roles in formation of the embryonic brain, eye, heart, cartilage or hematopoiesis. Loss-of-function studies of Pbx1, 2 and 3 and Meis1 documented specific functions in embryogenesis, however, functional studies of Meis2 in mouse are still missing. We have generated a conditional allele of Meis2 in mice and shown that systemic inactivation of the Meis2 gene results in lethality by the embryonic day 14 that is accompanied with hemorrhaging. RESULTS: We show that neural crest cells express Meis2 and Meis2-defficient embryos display defects in tissues that are derived from the neural crest, such as an abnormal heart outflow tract with the persistent truncus arteriosus and abnormal cranial nerves. The importance of Meis2 for neural crest cells is further confirmed by means of conditional inactivation of Meis2 using crest-specific AP2α-IRES-Cre mouse. Conditional mutants display perturbed development of the craniofacial skeleton with severe anomalies in cranial bones and cartilages, heart and cranial nerve abnormalities. CONCLUSIONS: Meis2-null mice are embryonic lethal. Our results reveal a critical role of Meis2 during cranial and cardiac neural crest cells development in mouse.
- MeSH
- chrupavka abnormality embryologie MeSH
- crista neuralis embryologie metabolismus MeSH
- forkhead transkripční faktory biosyntéza genetika MeSH
- hlavové nervy embryologie MeSH
- homeodoménové proteiny genetika MeSH
- krvácení genetika MeSH
- lebka embryologie inervace MeSH
- myši inbrední C57BL MeSH
- myši knockoutované MeSH
- myši MeSH
- represorové proteiny biosyntéza genetika MeSH
- srdce embryologie MeSH
- transkripční faktor SOX9 biosyntéza genetika MeSH
- vrozené srdeční vady embryologie genetika MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
Prehľadová práca prináša širší pohľad na význam a postavenie ultrasonografickej (USG) diagnostiky v manažmente tehotností žien s preexistujúcim diabetes mellitus. Zameraná je na miesto USG pri hodnotení stavu a vývoja plodu ohrozeného diabetom tehotnej ženy. Pre prehľadnosť je tematika členená podľa trimestrov tehotnosti a pokrýva spektrum súvisiacich problémov, ku kterým patria: datovanie tehotnosti, včasná predikcia jej komplikácií, ultrasonografický skríning vrodených malformácií a aneuploídie plodu, fetálna echokardiografia a hodnotenie rastu aj stavu plodu ku koncu tehotnosti.
This review provides a broader view of the importance and role of ultrasound diagnostics in the management of pregnancies complicated with pre-existing diabetes mellitus. A stress is put on the role of ultrasound diagnostics in evaluating the status and development of the fetus at risk due to diabetes mellitus of a pregnant woman. For its clarity, the issue is broken down by trimesters of pregnancy and covers a range of related topics including: dating of pregnancy, early prediction of its complications, ultrasound screening for congenital malformations and fetal aneuploidy, fetal echocardiography and assessment of the status and growth of the fetus at the end of pregnancy.
- MeSH
- druhý trimestr těhotenství MeSH
- echokardiografie MeSH
- fetální srdce ultrasonografie MeSH
- komplikace diabetu MeSH
- lidé MeSH
- makrosomie plodu ultrasonografie MeSH
- nemoci plodu ultrasonografie MeSH
- plod abnormality MeSH
- první trimestr těhotenství MeSH
- těhotenství při diabetu * MeSH
- těhotenství MeSH
- třetí trimestr těhotenství MeSH
- ultrasonografie prenatální * metody MeSH
- vrozené srdeční vady embryologie ultrasonografie MeSH
- vrozené vady * embryologie ultrasonografie MeSH
- vývoj plodu MeSH
- Check Tag
- lidé MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- Publikační typ
- přehledy MeSH
Cardiovascular malformations are the most common manifestation of diabetic embryopathy. The molecular mechanisms underlying the teratogenic effect of maternal diabetes have not been fully elucidated. Using genome-wide expression profiling, we previously demonstrated that exposure to maternal diabetes resulted in dysregulation of the hypoxia-inducible factor 1 (HIF-1) pathway in the developing embryo. We thus considered a possible link between HIF-1-regulated pathways and the development of congenital malformations. HIF-1α heterozygous-null (Hif1a(+/-)) and wild type (Wt) littermate embryos were exposed to the intrauterine environment of a diabetic mother to analyze the frequency and morphology of congenital defects, and assess gene expression changes in Wt and Hif1a(+/-) embryos. We observed a decreased number of embryos per litter and an increased incidence of heart malformations, including atrioventricular septal defects and reduced myocardial mass, in diabetes-exposed Hif1a(+/-) embryos as compared to Wt embryos. We also detected significant differences in the expression of key cardiac transcription factors, including Nkx2.5, Tbx5, and Mef2C, in diabetes-exposed Hif1a(+/-) embryonic hearts compared to Wt littermates. Thus, partial global HIF-1α deficiency alters gene expression in the developing heart and increases susceptibility to congenital defects in a mouse model of diabetic pregnancy.
- MeSH
- celogenomová asociační studie MeSH
- embryo savčí embryologie patologie MeSH
- faktor 1 indukovatelný hypoxií - podjednotka alfa * MeSH
- genetická predispozice k nemoci MeSH
- mutantní kmeny myší MeSH
- myši MeSH
- srdce embryologie MeSH
- svalové proteiny biosyntéza genetika MeSH
- těhotenství při diabetu genetika metabolismus patologie MeSH
- těhotenství MeSH
- vrozené srdeční vady embryologie genetika patologie MeSH
- vývojová regulace genové exprese * MeSH
- zvířata MeSH
- Check Tag
- myši MeSH
- těhotenství MeSH
- ženské pohlaví MeSH
- zvířata MeSH
- Publikační typ
- časopisecké články MeSH
- práce podpořená grantem MeSH
- MeSH
- ptáci abnormality embryologie MeSH
- vrozené srdeční vady embryologie vrozené MeSH
- vrozené vady embryologie klasifikace MeSH
- zvířata MeSH
- Check Tag
- zvířata MeSH
- Publikační typ
- kongresy MeSH
- MeSH
- kardiochirurgické výkony MeSH
- kojenec MeSH
- mimotělní oběh MeSH
- novorozenec MeSH
- plicní hypertenze MeSH
- předškolní dítě MeSH
- terapeutická hypotermie MeSH
- venae pulmonales abnormality chirurgie MeSH
- vrozené srdeční vady embryologie chirurgie patologie MeSH
- Check Tag
- kojenec MeSH
- novorozenec MeSH
- předškolní dítě MeSH
