Search PubMed⌕ Search

SEARCH · Search PubMed

Results for “PALATE”

Search indexed PubMed citations on genomics, clinical trials, systematic reviews and public health. Explore titles, authors and supplied subject terms, then open the PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 721 records · Page 40Linked to original sources
PubMed1989

Etiology of retinoic acid-induced cleft palate varies with the embryonic stage.

Retinoic acid (RA) has been shown to be teratogenic in many species, and 13-cis-RA is teratogenic in humans. Exposure to RA during embryonic morphogenesis produced a variety of malformations including limb defects and cleft palate. The type and severity of malformation depended on the stage of development exposed. The purpose of this study was to compare the effects of RA exposure in vivo on different stages of palate development. These results were compared to effects observed after exposure in organ culture. The vehicle used in RA dosing was also shown to be a major factor in the incidence of RA-induced cleft palate. For the in vivo studies, RA (100 mg/kg) in 10 ml corn oil/kg was given p.o. on gestation day (GD) 10 or 12, and the embryos were examined on GD 14 and 16. Exposure to RA in an oil:DMSO vehicle resulted in much higher incidences of cleft palate than were observed after dosing with RA in oil only. After exposure on GD 10, to RA, small palatal shelves formed which did not make contact and fuse on GD 14. The medial cells did not undergo programmed cell death. Instead, the medial cells differentiated into a stratified, squamous, oral-like epithelium. The RA-exposed medial cells did not incorporate 3H-TdR on GD 14 or 16, but the cells expressed EGF receptors and bound 125I-EGF. In contrast, RA-induced clefting after exposure on GD 12 did not involve growth inhibition. Shelves of normal size formed and made contact, but because of altered medial cell differentiation did not fuse. Medial cells differentiated into a pseudostratified, ciliated, nasal-like epithelium. This response was produced in vivo at exposure levels which produced cleft palate, and after exposure of palatal shelves to RA in vitro from GD 12-15. The medial cells exposed on GD 12 incorporated 3H-TdR on GD 14, expressed EGF receptors, and bound 125I-EGF. The responses to RA which lead to cleft palate differed after exposure on GD 10 or 12, and the pathways of differentiation which the medial cells followed depended on the developmental stage exposed.

Animals↗
PubMed1990

Morphological observations in normal primary palate and cleft lip embryos in the Kyoto collection.

Normal developmental events during human primary palate formation and alterations associated with cleft lip remain poorly defined. The purpose of this study was to analyze serially sectioned human embryos to identify morphological changes during normal palatal closure and alterations associated with failure of palatal formation. Normal and cleft embryos from the histological collection at the Congenital Anomaly Research Center at the University of Kyoto were studied and photographed for detailed evaluation. Seven serially sectioned cleft lip embryos of stages shortly after primary palate formation (Streeter-O'Rahilly stages 19, 20, and 22) with unilateral or bilateral clefts with varying degrees of clefting were studied. In the normal Kyoto embryos, initial nasal fin (epithelial seam) formation was observed between the medial nasal process and the lateral nasal and maxillary processes at stage 17. During stages 18 and 19, the nasal fin epithelium was replaced by an enlarging mesenchymal bridge, as the maxillary processes united with the medial nasal processes to form the primary palate. The most prominent features observed in the cleft embryos were a reduced thickness of mesenchymal bridging between the medial nasal and maxillary processes, with an excessive amount of epithelium at the junctions between these processes. With ingrowth of the maxillary processes, greater cell dispersion and apparent extracellular matrix accumulation were observed in the medial nasal region. During closure of the primary palate, terminal branches of the maxillary nerve crossed the mesenchymal bridge to the medial nasal region. The partial clefts had reduced maxillary ingrowth and smaller union areas with the medial nasal process. Detailed studies of experimental animal models are required to identify regional growth required for contact between the facial prominences, to clarify the mechanisms of mesenchymal ingrowth and epithelial displacement during palatal formation, and to identify local and/or general factors causing alterations that lead to primary palatal clefting.

Cleft Lip↗
PubMed1997

Transforming growth factor-beta 1 modulates myofibroblastic phenotype of rat palatal fibroblasts in vitro.

The effects of transforming growth factor-beta 1 (TGF-beta 1) on normal rat palatal fibroblasts in vitro were investigated in the present study in order to unravel the precise mechanisms by which the phenotypic modulation of fibroblasts occurs during the scar formation process. TGF-beta 1 dramatically changed the morphology of normal palatal fibroblasts from polygonal into an elongated shape, which was very similar to that of fibroblasts derived from experimental immature scar tissue in rat palatal mucosa. This morphological transition was concomitant with an increase in the expression of alpha-smooth muscle (alpha-SM) actin protein, a marker for myofibroblasts, when determined by immunocytochemistry. An immunoblot study also revealed that alpha-SM actin expression in palatal fibroblasts became evident after 24 h of TGF-beta 1 treatment and increased time-dependently up to 72 h. Northern blot analysis showed that TGF-beta 1 stimulated endogenous TGF-beta 1 mRNA expression in palatal fibroblasts within 24 h. Neither epidermal growth factor nor basic fibroblast growth factor had any effect on either alpha-SM actin expression or TGF-beta 1 mRNA expression. Pretreatment of palatal fibroblasts with TGF-beta 1 significantly increased the contractile capacity in a three-dimensional collagen gel culture, even when the culture medium was deprived of TGF-beta 1 for 72 h of the experimental period. Moreover, the contractility of scar fibroblasts, which highly expressed alpha-SM actin protein and TGF-beta 1 mRNA, was significantly lowered by a neutralizing antibody to TGF-beta 1. These data strongly suggest that TGF-beta 1 is a potential inducer of phenotypic expression of myofibroblasts in palatal fibroblasts and that auto-induction of TGF-beta 1 mRNA expression may play an important role in the scar formation process in palatal mucosa.

Actins↗
PubMed2006

[The influence of the Tübingen soft palate plate and early cleft closure on swallowing and Eustachian tube function in children with Pierre Robin sequence].

CURRENT KNOWLEDGE: Children with Pierre Robin sequence (PRS) typically have difficulty with bolus transport and swallowing. Due to velopharyngeal insufficiency caused by the cleft palate, a high percentage of the children affected also have impaired Eustachian tube function. AIMS OF THE STUDY: In the literature, substantial information may be obtained on conductive hearing loss in PRS patients; however, no study has yet been performed to investigate whether wearing a soft palate plate and relatively early surgical cleft palate closure positively influence Eustachian tube function. In the present study this question was investigated. METHODS AND RESULTS: A total of 41 PRS children, 27 girls and 14 boys, were included in the study and were examined for hearing ability prior to and after surgical cleft palate closure. All of the children had been wearing a Tübingen soft palate plate until surgical cleft palate closure, which occurred at an age of 3-13 months (mean age 7.3 months). Based on data obtained prior to surgery by BERA, otoacoustic emissions and tympanometry, a hearing loss of more than 30 dB was diagnosed in 68.4% of the children. After 3-6 months, normal hearing ability was found in 70%. CONCLUSIONS: Wearing the Tübingen soft palate plate, and the improved swallowing function resulting from this, as well as early surgical cleft palate closure had a very positive impact on the hearing ability of the children included in the study.

Auditory Threshold↗
PubMed1995

Review of the interaction between TCDD and glucocorticoids in embryonic palate.

2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) is an environmental contaminant that produces adverse biological effects including developmental toxicity and teratogenesis. In the mouse embryo, TCDD induces cleft palate and hydronephrosis. The synthetic glucocorticoid, hydrocortisone (HC), induces cleft palate and a potent, synergistic interaction has been observed between TCDD and HC in C57BL/6N embryonic mice. The morphology and etiology of TCDD- and HC-induced clefts are distinctly different with formation of small palatal shelves following HC exposure and failure of normally-sized shelves to fuse after TCDD treatment. Each exposure also alters expression of several growth factors. When EGF, TGF alpha, EGF receptor, and the TGF beta's are considered as a combinatorial, interacting set of regulators, TCDD and HC each produce a unique pattern of increased and/or decreased expression across the set. The interaction of HC and TCDD results in a cleft palate whose etiology most closely resembles that observed after HC exposure, i.e. small palatal shelves. HC+TCDD-exposure also produces a pattern of growth factor expression which closely resembles that seen after HC. Both TCDD and HC act through receptor-mediated mechanisms and each compound has its own receptor. The Ah receptor (AhR) binds TCDD and the glucocorticoid receptor (GR) binds HC. On gestation day (GD) 14, in the embryonic palate exposed to TCDD, the AhR was downregulated and the GR expression increased. Conversely, following HC exposure, the GR was downregulated and AhR levels were elevated. HC+TCDD produced increased expression of both receptors and this pattern would be predicted to produce HC-like clefts as the GR-mediated responses would result in small palatal shelves. The observed cross-regulation of the receptors is believed to be important in the synergistic interaction between TCDD and HC for the induction of cleft palate.

Abnormalities, Drug-Induced↗
PubMedDate not supplied

All-trans-retinoic acid-induced variant patterns of palatal rugae in Crj:SD rat fetuses and their potential as indicators for teratogenicity.

We determined the critical period for cleft palate formation in the presence of all-trans-retinoic acid (RA) and defined anomalous patterns within the variants of palatal rugae. The total incidence of variant patterns of palatal rugae in rat fetuses treated with RA at 40 mg/kg on gestation days 13 and 14 dramatically increased with concurrent induction of cleft palate. Correspondence analysis connected the variant patterns of palatal rugae, such as median discontinuity, extra peaks, supernumerary ruga (extra type), shortness, fusion, and bifurcation, with cleft palate. Therefore, these variants were concluded to be anomalous. The incidence of the anomalous patterns of palatal rugae was about 10 times that of cleft palate, and consequently, these anomalies might be sensitive indicators of the teratogenicity of a chemical.

Animals↗
PubMed1994

Effect of timing and method of closure of isolated cleft palate on development of dental arches from 3 to 6 years of age.

Development of the dental arches from 3 to 6 years of age was followed in 120 children with isolated cleft palate (ICP) and in 50 non-cleft (NONC) children. In 60 of the ICP children the palate had been repaired at the age of 1.8 years (SD = 0.2) and in the other 60 at the age of 1.1 years (SD = 0.1). In both groups the one-stage soft and hard cleft palate closure had been performed using the mucoperiosteal palatal V to Y push-back technique (Veau-Wardill-Kilner) or the Cronin modification. The purpose of this study was to compare the effect of the two different ages and the two different methods of palatal repair on the development of dental arches. The growth increment in maxillary canine and molar width, and posterior palatal height during the 3-year period was greater in the group with late palatal repair. In children with no secondary palatal repair, when the primary repair had been done with the V to Y method, the increase in maxillary canine width was greater than with the Cronin modification. On the other hand, when the V to Y technique was used, velopharyngoplasties were more frequent. The means of maxillary canine and molar width decreased in children with velopharyngoplasties, and increased in the others. Dental arches of ICP children were significantly smaller than those of NONC children, and the discrepancy increased during the period from 3 to 6 years of age, and increased more in the maxilla than in the mandible.

Age Factors↗
PubMed2003

Quantitative effects of a nickel-titanium palatal expander on skeletal and dental structures in the primary and mixed dentition: a preliminary study.

The present study analysed the six-month effects of a nickel-titanium (NiTi) palatal expander on the dental and palatal structures of four primary (mean age 5.8 years) and nine mixed dentition children (mean age 8.7 years), with a posterior unilateral crossbite. Standardized dental and palatal landmarks were digitized using a three-dimensional (3D) electromagnetic instrument. Collected data were analysed with geometric-mathematical models. During a six-month interval, the natural growth and development of the dental arches and hard tissue palate was negligible, as assessed in seven control children (two in the primary dentition, mean age 4.4 years; five in the mixed dentition, mean age 7.7 years). In all children the crossbite was completely corrected. Indeed, dental expansion was always more than or corresponded to the palatal expansion. A smoothing of the size-independent (shape) palatal curvature in the transverse plane was observed. No differences in maximum palatal height were noted. Symmetrical derotation of the anchorage teeth in a distal direction occurred in almost all children. The inclination of the facial axis of the clinical crown (FACC) in the anatomical transverse plane of those teeth with differences between dental and palatal expansion always showed significant modifications (vestibular inclination up to 16.7 degrees). The clinical crown height of anchorage teeth remained nearly the same in all patients. No significant modifications in mandibular arch size were observed. The increase in maxillary arch width, especially in younger children, was probably due to a combination of different effects: opening of the midpalatal suture, tipping of the alveolar process, and molar tipping.

Alveolar Process↗
PubMed2006

Regional heterogeneity in the developing palate: morphological and molecular evidence for normal and abnormal palatogenesis.

Development of the mammalian secondary palate involves the growth, elevation, medial elongation and midline fusion of palatal shelves. Recent morphological and molecular studies on palatogenesis suggest that the developing palate is not a homogeneous organ but each part may behave differently during organogenesis. Especially, some key molecules involved in palate development have been shown to exhibit heterogeneous patterns of expression in the palatal tissue. Therefore it seems necessary to recognize the regional heterogeneity of the developing palate along the dorsoventral and anteroposterior axes when analyzing the mechanisms of normal and abnormal morphogenesis. Based on recent studies, we discuss the issue of the regional heterogeneity in the fetal palate and propose a principle that divides the fetal palate into several regions from the morphological and molecular standpoint.

Animals↗
PubMed1992

Minuscule submucous cleft palate. Cadaver study.

Otitis media is almost universal in cleft palate patients, at least during infancy. A lesser cleft manifestation, the occult submucous cleft palate, is identifiable in living patients by surgical dissection or flexible fiberoptic nasopharyngoscopy. We addressed the hypothesis that an even more subtle form of submucous cleft palate, involving both an abnormal musculus levator veli palatini and an abnormal musculus uvulae, is associated with otitis media. We studied 35 adult human cadaver specimens for histologic and infrared photographic transillumination evidence of what we have identified as the minuscule submucous cleft palate. None of the specimens had evidence of clinical otitis media, or clinical abnormality of the palate. Approximately one fifth of the specimens had evidence of minuscule submucous cleft palate: minimal bulk of the musculus uvulae and haphazard organization of the fibers of the musculus levator veli palatini. These data support the nasopharyngoscopic inference that in occult submucous cleft palate, there is both hypoplasia of the musculus uvulae and abnormal orientation of the fibers of the musculus levator veli palatini. Although not significant statistically, a trend was suggested for minuscule submucous cleft palate to be associated with indicators of prior otitis media.

Adult↗
PubMed2004

Deficient cell proliferation in palatal shelf mesenchyme of CL/Fr mouse embryos.

How secondary palate formation is affected in the cleft lip genotype remains poorly understood. The purpose of this study was to analyze regional patterns of cell proliferation in CL/Fr mouse embryos with or without cleft lip. Pairs of palatal shelves were dissected at E13.5 from CL/Fr normal embryos (CL/Fr-N), CL/Fr embryos with bilateral cleft lip (CL/Fr-BCL), and a control strain of C57BL embryos (C57BL). The explants were examined histologically after 48 hrs of organ culture. Cell kinetics for proliferation in the palatal shelves was examined at E13.5 by the bromodeoxyuridine method in vivo. The CL/Fr-BCL palates fused as well as the CL/Fr-N palates in vitro. There were inter-group differences in the absolute number of BrdU-positive cells and the ratio of positive/(positive+negative) cells in the palate's mesenchyme (C57BL > CL/Fr-N > CL/Fr-BCL) and epithelium (C57BL > CL/Fr-N = CL/Fr-BCL). These findings indicate that a cleft palate follows reduced cell proliferation of secondary palatal mesenchyme in CL/Fr mice.

Animals↗
PubMed2005

Cyclic motion of the soft palate in feeding.

The soft palate moves rhythmically during feeding, but the timing and frequency of this motion are not known. We tested the hypothesis that cyclic soft palate motion is temporally linked to cyclic jaw movement. Nine healthy, asymptomatic human subjects with normal dentition ate solid food coated with barium. Videofluorographic recordings showed that rhythmic motions of the soft palate during mastication were linked temporally to jaw motion. Soft palate motion occurred in every recording but not in every jaw cycle. The soft palate moved upward as the jaw opened, but the nasopharynx was not sealed. During swallowing, however, the soft palate invariably elevated during the intercuspal phase of jaw motion, sealing the nasopharynx. The frequency of soft palate cycles was lowest early in a feeding sequence and gradually increased as the sequence progressed from ingestion to swallowing. We conclude that cyclic movement of the soft palate in feeding is temporally linked to jaw motion.

Adult↗
PubMed2003

Conditional inactivation of Tgfbr2 in cranial neural crest causes cleft palate and calvaria defects.

Cleft palate and skull malformations represent some of the most frequent congenital birth defects in the human population. Previous studies have shown that TGFbeta signaling regulates the fate of the medial edge epithelium during palatal fusion and postnatal cranial suture closure during skull development. It is not understood, however, what the functional significance of TGFbeta signaling is in regulating the fate of cranial neural crest (CNC) cells during craniofacial development. We show that mice with Tgfbr2 conditional gene ablation in the CNC have complete cleft secondary palate, calvaria agenesis, and other skull defects with complete phenotype penetrance. Significantly, disruption of the TGFbeta signaling does not adversely affect CNC migration. Cleft palate in Tgfbr2 mutant mice results from a cell proliferation defect within the CNC-derived palatal mesenchyme. The midline epithelium of the mutant palatal shelf remains functionally competent to mediate palatal fusion once the palatal shelves are placed in close contact in vitro. Our data suggests that TGFbeta IIR plays a crucial, cell-autonomous role in regulating the fate of CNC cells during palatogenesis. During skull development, disruption of TGFbeta signaling in the CNC severely impairs cell proliferation in the dura mater, consequently resulting in calvaria agenesis. We provide in vivo evidence that TGFbeta signaling within the CNC-derived dura mater provides essential inductive instruction for both the CNC- and mesoderm-derived calvarial bone development. This study demonstrates that TGFbeta IIR plays an essential role in the development of the CNC and provides a model for the study of abnormal CNC development.

Animals↗
PubMed1994

Comparison of velopharyngeal growth patterns between cleft lip and/or palate patients requiring or not requiring pharyngeal flap surgery.

This investigation compares the patterns of velopharyngeal growth in cleft lip and/or palate patients. Those who had velopharyngeal competence and acceptable speech are compared with those who presented with velopharyngeal incompetence requiring pharyngeal flap surgery or prosthesis later. Lateral cephalograms of 30 cleft palate only (CPO), 35 unilateral cleft lip and palate (UCLP), and 20 bilateral cleft lip and palate (BCLP) children of the Lancaster Cleft Palate Clinic were studied. These records were taken at 6 month intervals during the first 2 postnatal years and annually thereafter up to 6 years of age. Soft tissue landmark points in the velopharyngeal region were digitized. Length and thickness of the soft palate and height and depth of the nasopharynx were measured. Evaluation of the growth curves of these four cephalometric variables indicated only two significant differences between children who later required pharyngeal flap surgery and those who did not. These differences were found in the growth in length of the soft palate of the CPO group and in the growth in depth of the nasopharynx of the BCLP group. Based on the present cephalometric data, it is impossible to predict at an early age those cleft lip and/or palate patients who will later require pharyngeal flaps.

Cephalometry↗
PubMed1995

Pharyngeal flaps after one- and two-stage repair of the cleft palate: a 25-year review of 520 patients.

Between 1962 and 1976, a one-stage surgical procedure was performed on 328 cases of cleft lip and palate or isolated cleft palate. From 1977 to 1986, a two-stage surgical procedure was performed on 192 patients. After one-stage repair, 22 (6.7%) required a pharyngeal flap at the age of 6 years, and 13 (7%) required a flap after two-stage repair. When the patients were 14 years or older, 56 (17%) needed a flap after one-stage repair, and 14 (24%) required a flap after two-stage repair. Two-stage repair at 24 months and 5.2 years resulted in more patients in need of pharyngeal flaps than those who had repair at 12 to 18 months and 3 years. In both groups, at age 10, the incidence of flaps was approximately 20% after closure of isolated cleft palate involving the hard palate, with 11 to 12% in patients with unilateral cleft lip and palate (UCLP) or clefts of the soft palate only, and 14 to 16% in patients with bilateral cleft lip and palate (BCLP). The pharyngeal flap was more often used in girls than in boys, especially in cases with CP only. Approximately 85% of the flaps were carried out before the age of 10 years, and only a few flaps may have been related to involution of the adenoid. The incidence of fistulas was higher after one-stage repair of cleft lip and palate (CLP) (p < .05) and lower in patients with CP only (p < .05), compared with the results after two-stage repair. Pharyngeal flaps were slightly more common after two-stage repair.(ABSTRACT TRUNCATED AT 250 WORDS)

Adolescent↗
PubMed1998

Unilateral cleft lip with or without cleft palate and handedness: is there an association?

OBJECTIVE: The purpose of this study was to investigate the possibility of a relationship between the side of occurrence of unilateral clefting of the lip and/or palate and handedness, also taking into account the type of the initial cleft condition, a factor that has not been adequately assessed in previous studies. DESIGN: This was a retrospective study. SETTING: Division of Orthodontics, The Hospital for Sick Children, Toronto, Canada, and Cleft Lip and Palate Program, Children's Hospital, Winnipeg, Canada. PARTICIPANTS: Subjects were 289 patients (176 males and 113 females) 9 years of age or older presenting with a history of unilateral clefts of the lip with or without the palate. Of these patients, 217 were recruited from the patient pool of the Orthodontic Clinic at the Hospital for Sick Children in Toronto. The remaining 72 were selected from the registry of the Cleft Lip and Palate Program of the Children's Hospital in Winnipeg. Any syndromic cases were excluded from the sample. MAIN OUTCOME MEASURES: Assessment of handedness was performed by asking the patients to fill out a multi-item questionnaire in which patients were asked to identify which hand they would use for different tasks. The side and type of the initial cleft condition were identified by reviewing each patient's hospital chart and by cross-referencing with clinical examination. Statistical evaluation of the results was performed by using the chi-square test. RESULTS: There was a significantly larger number of left-sided clefts (198) in the sample than right-sided clefts (91), (p < .001). The proportion of left-sided clefts among left-handers (84.6%) was higher than that among right-handers (66.8%). However, the relationship between side of cleft and handedness was not statistically significant (p = .185). Clefts of the primary palate only seemed to occur on the left side 3.5 times more often than on the right, whereas the corresponding ratio of left:right manifestation for clefts of the primary and secondary palate was 1.8:1. The difference was statistically significant (p < .05). CONCLUSION: The findings of this study confirm the affinity of unilateral clefts for the left side but suggest that there are differences between clefts of the primary palate only and clefts of the primary and secondary palate. Also, non-right-handed patients show a greater predilection for having a cleft on the left side than do right-handed patients.

Chi-Square Distribution↗
PubMed2000

A comparative study of prespeech vocalizations in two groups of toddlers with cleft palate and a noncleft group.

OBJECTIVE: This study examined the prelinguistic contoid (consonant-like) inventories of 14 children with unilateral cleft lip and palate (C-UCLP) at 13 months of age. The children had received primary veloplasty at 7 months of age and closure of the hard palate was performed at 3-5 years. The results of this investigation were compared to results previously reported for 19 children with cleft palate and 19 noncleft children at the age of 13 months. The children with clefts in that study received a two-stage palatal surgery. This surgical procedure was formerly used at our center and included closure of the lip and hard palate at 3 months of age and soft palate closure at 22 months of age. DESIGN: Retrospective study. SETTING: The participants were videorecorded in their homes during play with their mothers. The videotapes were transcribed independently by three trained speech pathologists. PATIENTS: Fourteen consecutive patients born with C-UCLP and no known mental retardation or associated syndromes served as subjects. RESULTS: The children who received delayed closure of the hard palate demonstrated a significantly richer variety of contoids in their prespeech vocalizations than the cleft children in the comparison group. Both groups of subjects with clefts had significantly fewer plosives in their contoid inventory than the noncleft group, and there was no difference regarding place of articulation between the group that received delayed closure of the hard palate and the noncleft group.

Age Factors↗
PubMed2001

Alteration of apoptosis in cleft palate formation and ectomesenchymal stem cells influenced by retinoic acid.

It has been shown that apoptosis is involved in normal embryonic development. The aim of the present study was to elucidate the role and alteration of apoptosis in the pathogenesis of cleft palate induced by retinoic acid (RA) and the ectomesenchymal stem (EMS) cells influenced by RA. RA was administered by gavage to pregnant C57BL/6N strain mice in the experimental group, and the control group received oil alone. Pregnant mice were killed at set periods of time thereafter and histologically analyzed. EMS cells explanted from the palatal shelves of embryonic mice were cultured and characterized by immunohistochemistry, growth curves and population-doubling time. The alterations of apoptosis of EMS cells and developing palatal shelves influenced by RA were evaluated by the terminal deoxynucleotidyl transferase-mediated UTP-biotin nick end-labeling (TUNEL) method. RA-treated mice showed formation of cleft palates resulted from the small size of the palatal shelves and their failure to lift. TUNEL staining showed that the number of apoptotic mesenchymal cells in palatal shelves in the RA-treated mice was increased significantly when compared with the control group. The primary culture of EMS cells proceeded successfully. The population-doubling time of RA-treated cells was much longer compared with non-treated EMS cells. RA also dramatically increased the number of apoptotic cells in EMS cells in vitro. We concluded that EMS cells are the crucial cells in palate development. RA could inhibit the proliferation and induced the apoptosis of EMS cells. The inhibition of growth and excess apoptosis of EMS cells may contribute to the formation of cleft palate and other orofacial congenital malformations.

Animals↗