Maternal diabetes (types 1 and 2) induces a broad array of congenital malformations, including neural tube defects (NTDs), in humans. One of the difficulties associated with studying diabetic embryopathy is the rarity of individual malformations. In an attempt to develop a sensitive animal model for maternal diabetes-induced NTDs, the present study uses chemically induced diabetes in an inbred mouse model with or without the splotch (Sp) mutation, a putatively nonfunctional allele of Pax3. Pax3 deficiency has been associated with an increase in NTDs. Female C57BL/6J mice, either with or without the Sp allele, were injected intravenously with alloxan (100 mg/kg), and plasma glucose was measured 3 days later. A wide range of hyperglycemia was induced, and these diabetic mice were bred to C57BL/6J males, some carrying the Sp allele. Gestational-day-18 fetuses were examined for developmental malformations. Fetuses from matings in which either parent carried the Sp allele were genotyped by polymerase chain reaction. Maternal diabetes significantly decreased fetal weight and increased the number of resorptions and malformations, including NTDs. A significant correlation was found between the level of maternal hyperglycemia and the malformation rate. The sex ratio for live fetuses in diabetic litters was significantly skewed toward male fetuses. Matings involving the Sp allele yielded litters with significantly higher percentages of maternal diabetes-induced spina bifida aperta but not exencephaly, and this increase was shown to be associated with the presence of a single copy of the Sp allele in affected fetuses. Thus, Pax3 haploinsufficiency in this murine model of diabetic embryopathy is associated with caudal but not cranial NTDs.

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The hydration of hyaluronic acid (HA) accumulated in the secondary palatal processes is expected to exert an intrinsic tissue pressure that could, in part, provide the impetus for shelf reorientation. Glycosaminoglycans were histochemically localized in the A/J mouse palate during development (days 12 to 15) by specific enzymatic degradation followed by preferential staining with alcian blue under differential pH or MgCl2 concentration. The presence of HA and chondroitin sulphates A and C (CS) was demonstrated in proportions that differed regionally. At the time of reorientation (days 14 to 15) HA was the predominant staining component, being distributed according to the relative prominence of extracellular spaces (ECS). HA was present in higher concentration in the anterior than the posterior part of the palate, particularly in an area of low cell density adjoining the CS-rich mesenchyme of the maxillary process. This arrangement suggests that the maxillary process might provide a resilient incompressible structural base for the palate as its HA-rich ECS expands. Sulphated GAG, with CS being the predominant component, was localized for the most part on the oral-side mesenchyme both in the anterior and posterior palate. The most intense staining of sulphated proteoglycans occurred in association with the basal lamina along the presumptive oral-side. Mesenchymal cells along this region appeared condensed and may have been stabilized by these sulphated GAG providing structural constraints which might function in palate morphogenesis.

Pregnant rats were exposed three times daily to immobilization stress during gestational Days 15-19. The behavior of their offspring was compared with the behavior of offspring from unstressed control mothers. Although the stress procedure decreased the weight gain of mothers during pregnancy, it slightly but significantly increased the weight of their offspring at birth and at weaning. On postnatal Day 10, prenatally stressed pups returned to their home cage more quickly than did prenatally unstressed control pups during a nest odor discrimination task, but no differences between groups in the number of correct responses were found. On postnatal Days 70-72, prenatally stressed offspring showed increased exploratory activity in a complex tunnel maze compared with control offspring. On postnatal Day 80, analgesia induced by stress (swimming for 3 min in cold water) was determined (tail flick latency). The degree of stress-induced analgesia was smaller in prenatally stressed rats than in control rats. These data suggest that the effects of prenatal stress on behavior are most clearly discernable when such animals are confronted with a novel or stressful situation.