Effects of Fetus Weight, Dam Strain, Dam Weight, and Litter Size on the Craniofacial Morphogenesis of CL/Fr Mouse Fetuses Affected with Cleft Lip and Palate

Abstract

Objective: This study examined the factors related to the morphogenesis of the craniofacial complex of the CL/Fr mouse fetus affected with CLP based on the findings of a lateral cephalogram. Design: Embryo transfer experiments were performed to determine the effect of the fetus weight, dam strain, dam weight, and litter size on the intra-uterine craniofacial morphogenesis of CL/Fr mouse fetuses. On the 18th gestational day, each pregnant dam that had received CL/Fr mouse embryos was laparotomized to remove the transferred fetuses that had developed in the uteri of the cleft lip and palate (CLP)-susceptible CL/Fr strain dam and the CLP-resistant C57BL strain dam. A cephalometric observation of the craniofacial morphology of each fetus was subsequently performed. Results: Based on a multiple regression analysis, the standardized partial regression coefficients of the affected fetus weight, the dam weight, and the litter size on the maxillary size of the affected CL/Fr fetus were 0.71 (p < .01), 0.03, and −0.07. According to a least-squares analysis of variance, the dam strain effect in addition to the effect of the affected fetus weight on the maxillary size and the cranial size of the affected fetuses was significant (p < .01 for cranial size, p < .05 for maxillary size) and close to a significant level (p = .09) for the mandibular size of the affected fetuses. The adjusted maxillary size and cranial size after statistically eliminating the effects of the affected fetus weight, dam weight, and lifter size on each original craniofacial size of the affected fetuses that had developed in the CL/Er dam strain were also significantly smaller than those of the affected fetuses that had developed in the C57BL dam strain. Conclusions: The present results indicate that the craniofacial growth of the CL/Fr mouse fetus affected with CLP increased in proportion to the fetus weight. The dam strain effect, in addition to the effect of the affected fetus weight, could thus not be ignored when the etiology of the spontaneous CLP was examined, while the uterine environment, provided by the CL/Fr strain dam, retarded the intra-uterine craniofacial growth of the affected fetuses. It was therefore concluded that the dam strain effect, as well as the effect of the affected fetus weight, both play an important role on the craniofacial morphogenesis of the CL/Fr strain of the affected fetuses that developed in both strain dams.

Taking it to the max: The genetic and developmental mechanisms coordinating midfacial morphogenesis and dysmorphology

“…Studies in monozygotic and dizygotic twins, where concordance for CLP is approximately 50 and 5%, respectively, highlight the likely relative contributions of both genes and environment (3–5). Significantly, these twin studies suggest that the maternal intrauterine environment and or nutritional status of the fetus may be a prominent environmental factor in determining the presentation of CLP, a conclusion consistent with findings from original maternal nutritional deficiency studies (6) and embryo transfer experiments (7) in rodents. More recently, breeding experiments between A/strain mice (which represent one of very few mouse models for non‐syndromal CLP) and mice of a different, non‐susceptible genetic background have clearly reaffirmed this significant maternal affect (8).…”

“…The incidence of CLP in offspring of these A/strain mice varies from 24% (when mothers are of the A/strain and fathers are of a strain not susceptible to CLP) to 8% (when fathers are the only parent of A/strain origin) (8). The strain therefore also affords a unique opportunity to investigate the significant maternal influences on the incidence of non‐syndromal CLP, a factor that has been appreciated for many years (6, 7) but for which there are few clues. This mouse model clearly offers an excellent system in which to study the epistatic nature of the interactions between at least one set of loci that influence the presentation of non‐syndromal CLP.…”

Effects of quinine sulfate- an antimalarial drug on palatal growth in developing mice embryo: A histopathological study

“…19,20 Palatal defects is one of the most serious congenital anomalies in humans that cause a sucking (breast feeding) problem in newborn babies and a morphologic deformity that usually leads to death in newborn mouse offspring due to an insufficient ability to suck milk. 21 In humans, the frequency of palatal defects has been reported to increase in pregnant women affected with diabetes mellitus 22 or epilepsy. 23 The incidence of palatal defects are observed when methanol, 24 25 Triamcinolone acetonide, a synthetic glucocorticoid, 26 2,3,7,8-Tetrachlorodibenzop-dioxin (TCDD), a highly toxic halogenated aromatic hydrocarbon, 27 corticosteroid 28 and retinoic acid, 29,30 administered in the pregnant rodents.…”

Molecular contribution to cleft palate production in cleft lip mice

“…; Nonaka et al. ). There were no data of gender at E13.5 fetuses in our experiments, and the samples were randomly selected from the litters, resulting in no significant bias of gender.…”