Effects of embryonic hypoxia on lip formation

Nagaoka, Ryosuke; Okuhara, Shigeru; Satō, Yutaka; Amagasa, Teruo; Iseki, Sachiko

doi:10.1002/bdra.23000

Cited by 11 publications

(20 citation statements)

References 30 publications

(35 reference statements)

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“…In these embryos, cell proliferation activity was decreased in the fusion areas following downregulation of genes that are involved in lip formation. These results suggest that embryonic hypoxia during lip and palate formation induces apoptosis in physiologically hypoxic regions and HIF expression 17 . Therefore, we decided to evaluate if polymorphisms in HIF-1A are involved in the etiology of oral clefts in Brazilian families.…”

Section: Discussionmentioning

confidence: 76%

“…Some experimental in vivo studies 4 , 14 , 17 and observational studies 6 , 9 , 10 , 13 suggest that hypoxia in the first trimester can increase the risk of oral clefts. To the best of our knowledge, our study is the first to observe that hypoxia during embryonic development can cause oral clefts in zebrafish.…”

Section: Discussionmentioning

confidence: 99%

“…HIF-1A seems to play a very general role by signaling the existence of hypoxia to the transcriptional machinery in the nucleus of all cells 23 . An in vitro study with hypoxic embryos suggested the role of HIF-1A in oral cleft etiology 17 .…”

Section: Introductionmentioning

confidence: 99%

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Assessing the association between hypoxia during craniofacial development and oral clefts

et al. 2018

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ObjectivesTo evaluate the association between hypoxia during embryo development and oral clefts in an animal model, and to evaluate the association between polymorphisms in the HIF-1A gene with oral clefts in human families.Material and MethodsThe study with the animal model used zebrafish embryos at 8 hours post-fertilization submitted to 30% and 50% hypoxia for 24 hours. At 5 days post-fertilization, the larvae were fixed. The cartilage structures were stained to evaluate craniofacial phenotypes. The family-based association study included 148 Brazilian nuclear families with oral clefts. The association between the genetic polymorphisms rs2301113 and rs2057482 in HIF-1A with oral clefts was tested. We used real time PCR genotyping approach. ANOVA with Tukey's post-test was used to compare means. The transmission/disequilibrium test was used to analyze the distortion of the inheritance of alleles from parents to their affected offspring.ResultsFor the hypoxic animal model, the anterior portion of the ethmoid plate presented a gap in the anterior edge, forming a cleft. The hypoxia level was associated with the severity of the phenotype (p<0.0001). For the families, there was no under-transmitted allele among the affected progeny (p>0.05).ConclusionHypoxia is involved in the oral cleft etiology, however, polymorphisms in HIF-1A are not associated with oral clefts in humans.

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Section: Discussionmentioning

confidence: 76%

Section: Discussionmentioning

confidence: 99%

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Assessing the association between hypoxia during craniofacial development and oral clefts

et al. 2018

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“…Similarly, but non‐conclusive findings were published in India and in Japan . The deleterious effect of anaemia may be a consequence of embryonic hypoxia during the first trimester, since it has been described that hypoxia may result in insufficient growth of the facial processes in the developing embryo . The possible role of threatened abortion in the development of cleft palate was already described more than 40 years ago but since then similar findings have not been presented.…”

Section: Discussionmentioning

confidence: 99%

Maternal‐related factors in the origin of isolated cleft palate—A population‐based case‐control study

Ács

Bányai

Nemes

et al. 2020

Orthod Craniofacial Res

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Objects Isolated cleft palate (CPO) is the rarest form of oral clefting affecting 1‐25 per 10 000 newborns worldwide. There is increasing evidence for the different pathogenetic backgrounds of CPO and cleft lip with or without cleft palate. The role of environmental factors in the origin of non‐syndromic and syndromic CPO is unclear in most patients. The aim of this study was to estimate possible maternal risk factors in the origin of CPO. Setting and Sample Population The Hungarian Case‐Control Surveillance of Congenital Abnormalities contains data of 32 345 birth defect cases and 57 231 control newborns. The study samples included 751 cases with isolated CPO, 1196 matched controls and 57 231 population controls. Material and Methods Maternal diseases during pregnancy in cases and population controls were compared, and adjusted ORs with 95% CI were calculated in a multivariable unconditional logistic regression model. Results Beyond the well‐known robust female excess (58.9%)—maternal smoking (OR with 95% CI: 2.34, 1.94‐2.81) medically recorded maternal anaemia, threatened abortion and excessive vomiting in pregnancy were associated with a higher risk for CPO in the offspring. An elevated risk was found in Graves’ disease (OR: 4.30, 1.74‐10.62), epilepsy (OR: 4.64, 2.44‐8.82), migraine (OR: 2.82, 1.18‐6.76) and essential hypertension (OR: 2.33, 1.32‐4.10). Among acute diseases common cold (OR: 4.94, 3.48‐7.03), acute respiratory infections (OR: 4.20, 1.49‐11.82), influenza (OR: 2.95, 1.75‐4.95), pulpitis (OR: 7.85, 2.80‐22.03), cholecystitis (OR: 3.15, 1.16‐8.60), acute urinary tract infections (OR: 4.08, 2.22‐7.49) and pelvic inflammatory diseases (OR: 3.93, 1.62‐9.53) during pregnancy also were associated with an increased risk for developing CPO. Conclusion The findings of this study suggest that maternal diseases and lifestyle factors during the first trimester play a significant role in the development of isolated cleft palate.

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“…Nagaoka, et al (2012) described the relationship between embryonic hypoxia and UL formation. In hypoxic embryos, the activity of the LNP mesenchymal cell proliferation decreased being accompanied by reduced regulation of the genes being involved in UL formation resulting in insufficient growth of the facial processes [15].…”

Section: Peculiarities Of the Upper Lip Morphogenesis And Its Relatiomentioning

confidence: 99%

Peculiarities of the Upper Lip Morphogenesis and Its Relation to Facial Development

et al. 2017

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An appreciation of the fundamental principles associated with the development of the craniofacial structures is essential for attaining competency within the fields of facial surgery, dentistry and pediatrics. The objective of this literature review was to highlight the main stages and precise time ranges of human upper lip development, as well as to elucidate the fundamental mechanisms of normal morphogenesis and possible congenital malformations. The structures of the head and neck arise from the lateral portion of the neural tube, which forms five pairs of branchial arches. Recent studies have identified various molecular pathways (including Bmp, Fgf and Shh signaling) and genetic mechanisms in human face development. Primordial structures of the upper lip begin to appear early within the 6th week of ontogenesis; their development involves a number of highly coordinated, genetically programmed ontogenetic mechanisms that include growth and expansion of the facial prominences, programmed cell death, active fusion and breakdown of the epithelial seam between the initially freely maxillary, medial nasal, and lateral nasal processes. Defects of epithelial and mesenchymal fusion during upper lip formation result in orofacial cleft. Further research should be directed to studying normal ontogenesis at the molecular and topographical levels with the determination of critical periods, time ranges and developmental stages that are sensitive to teratogens.

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Effects of embryonic hypoxia on lip formation

Cited by 11 publications

References 30 publications

Assessing the association between hypoxia during craniofacial development and oral clefts

Assessing the association between hypoxia during craniofacial development and oral clefts

Maternal‐related factors in the origin of isolated cleft palate—A population‐based case‐control study

Peculiarities of the Upper Lip Morphogenesis and Its Relation to Facial Development

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