Folinic acid reduces cleft lip [CL(P)] in A/WySn mice.

Area of Science:

• Developmental Biology
• Teratology
• Pharmacology

Background:

• The A/WySnBk mouse strain exhibits a high incidence (25-35%) of spontaneous cleft lip and palate (CL(P)).
• Early embryonic development, particularly facial formation, is a critical period sensitive to teratogenic influences.

Purpose of the Study:

• To investigate the efficacy of folinic acid in preventing genetically predisposed CL(P) in a mouse model.
• To determine if continuous folinic acid administration during a critical developmental window reduces CL(P) frequency.

Main Methods:

• Pregnant A/WySnBk mice received continuous folinic acid via osmotic minipumps from gestation day (gd) 8.5-9.5.
• Control groups included untreated mice and those receiving saline via minipumps.
• Fetuses were examined on gd 18 for CL(P) and other abnormalities.

Main Results:

• Folinic acid treatment significantly decreased CL(P) incidence from 40.0% in controls to 10.2% (P<.001).
• The reduction was specific to folinic acid, as saline-treated controls showed no significant difference from untreated groups.
• No significant differences in mortality, litter size, or fetal weight were observed between groups.

Conclusions:

• Continuous administration of folinic acid during early gestation effectively ameliorates genetically determined CL(P) in mice.
• Folinic acid represents a potential therapeutic strategy for preventing CL(P).