Morphogenesis of hypoxia-induced cleft lip in CL/Fr mice.

Cleft lip with or without associated cleft palate [CL(P)], one of the most common human malformations, is in most cases, believed to be caused by a combination of genetic and environmental factors. Previous studies have shown that maternal respiratory hypoxia (10% O2) increases the incidence of CL(P) from the spontaneous level of 36% to 89% in CL/Fr mice. The current investigation was designed to study, morphologically, the developmental alterations of the primary palate primordia in CL/Fr embryos, following a reduction in maternal respiratory oxygen levels. Scanning electron microscopy was utilized to compare the development of 35-43 somite hypoxia and control (normoxia) embryos. Hypoxia increased the incidence of resorptions and increased the incidence of CL(P) in viable embryos, compared to normoxia. Debris, most of which was limited to the deeper aspects of the invaginating nasal placode, was present in hypoxia embryos at stages prior to primary palate fusion and was absent in comparably staged normoxia embryos. It is believed that this debris is cellular in nature and that associated retardation of placodal invagination is primarily responsible for the increased incidence of CL(P). Other effects on morphogenesis and/or growth retardation may also be contributing factors.