Potentiation of triamcinolone‐induced cleft palate in mice by maternal high dietary fat

Abstract

This study investigated whether the current range in dietary fat levels, which has arisen partly in response to some major health concerns, would affect frequency of congenital anomalies if continued into the period of early pregnancy. The effect of 5.6%, or 48% of calories from fat in the maternal diet, was tested on pregnant strain CD-1 mice injected with triamcinolone in doses of 0.01 mg, 0.02 mg, 0.04 mg, or 0.06 mg per day on days 11 through 14 of gestation. Frequency of cleft palate increased with increasing doses of triamcinolone, with clefts of the palate being rare at the two lower doses. No clefts appeared without triamcinolone on either diet. In combination with triamcinolone treatment, 226 fetuses exposed to a maternal low fat diet had normal palates and 86 had cleft palates. With exposure to high fat, 186 fetuses had normal palates and 101 had cleft palates, which was a significant increase in clefting (p < 0.05). Also, the latter group showed a greater degree of retardation in palate development (p < 0.05). Thus both a greater frequency and a more severe form of clefting support the conclusion that high dietary fat potentiated the cleft palate-producing effects of triamcinolone in mice.

Modeling anterior development in mice: Diet as modulator of risk for neural tube defects

“…In rodent models of diabetic pregnancy, supplementation of folate [Wentzel and Eriksson, 2005; Oyama et al, 2009], myo-inositol [Baker et al, 1990], Vitamins C and E [Ceder-berg and Eriksson, 2005; Wentzel and Eriksson, 2005], and arachidonic acid [Goldman et al, 1985] have all been shown to reduce the incidence of diabetes-induced developmental defects. Diet composition was also shown to affect the incidence of cleft palate induced by the teratogens Phenytoin [High and Kubow, 1994], triamcinolone [Zhou and Walker, 1993], or cortisone [Miller, 1977], but molecular sequelae are unknown in these models. Recently published reviews by Harris [2009] and Stover [2009] cover studies to understand the roles of folate metabolic pathway genes in cranial and spinal neural tube defects; therefore our focus here will be specifically on nutritional modulation of cranial defects in non-folate-pathway models.…”

Epigenetic implications in maternal diabetes and metabolic syndrome‐associated risk of orofacial clefts

“…Studies have found that maternal obesity and the Western (American) dietary pattern, which is high in fat and sodium and low in fruits and vegetables, are significantly associated with prevalence of CL/P (Blanco et al, 2015; Vujkovic et al, 2007). Zhou et al reported that a high fat maternal diet significantly increased the prevalence and severity of triamcinolone‐induced cleft palate in mice (Zhou & Walker, 1993). One mechanism by which a maternal diet affects development is through alterations in the epigenome, and high‐fat diet contributes to alterations in DNA methylation, histone methylation, and noncoding RNA expression (Li et al, 2013; Vucetic et al, 2010).…”