Accelerated embryonic development associated with increased risk of neural tube defects induced by maternal diet in offspring of SELH/Bc mice.
BACKGROUND
The SELH/Bc mouse strain has a high risk of the NTD, exencephaly, caused by multifactorial genetics. All SELH/Bc embryos have delayed elevation of neural folds; some never elevate (future exencephalics). Maternal diets affect SELH/Bc exencephaly rates: 25-35% on Purina Diet 5015 versus 5-10% on Purina Diet 5001. We hypothesized that in SELH/Bc, the diets affect maternal blood glucose and embryonic developmental rate.


METHODS
We compared mice fed the two diets. On GD 9.4 we tested maternal blood glucose and examined embryos for developmental age (somite count) and cranial neural fold morphology. We observed GD 14 exencephaly rates.


RESULTS
Diet 5015 caused fivefold more exencephaly (40 vs. 7% on GD 14), significantly higher mean maternal blood glucose in replicate experiments (6.3 vs. 5.5, p < .05; 6.3 vs. 5.3 mmol/L, p < .05), and significantly higher mean litter somite count on GD 9.4 (18.4 vs. 15.0, p < .05; 16.7 vs. 14.4 somites, p < .05). Among midrange embryos (15-16 somites), embryos from Diet 5015 were significantly shifted to earlier stages of midbrain fold morphology and had significantly more distance between the tips of the folds (p < .05).


CONCLUSIONS
In SELH/Bc mice, the 5015 diet causes higher maternal blood glucose, a faster overall embryonic developmental rate during neural tube closure, and delayed midbrain fold elevation relative to overall development. This pattern suggests that maternal dietary effects that modestly increase embryonic growth rate may exacerbate a lack of coordination between genetically delayed neural folds and normally developing underlying tissues, increasing risk of NTD.
Stoate
Katharine L
KL
Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, Canada.
Harris
Muriel J
MJ
Juriloff
Diana M
DM
D000818:Animals; D004622:Embryo, Mammalian / Q000378:metabolism; D047108:Embryonic Development; D005260:Female; D039382:Maternal Nutritional Physiological Phenomena; D051379:Mice; D008815:Mice, Inbred Strains; D009436:Neural Tube Defects / Q000196:embryology* / Q000209:etiology; D011247:Pregnancy; D012306:Risk