The Effect of Dietary Folic Acid Supplementation on Female Germ Cell Aneuploidy

Aneuploidy refers to cells with an abnormal number of chromosomes. In female germ cells, aneuploidy originates primarily during the first meiotic division of oogenesis as a result of chromosome segregation errors. Aneuploidy can lead to pregnancy loss and genetic defects in newborns. The incidence of aneuploidy in oocytes increases with advanced maternal age. There is evidence suggesting that dietary intervention can mitigate the effect of maternal age on oocyte aneuploidy. Folic acid, an essential B vitamin, is required for DNA synthesis, chromosome stability, methylation reactions, and proper gene expression; these processes are fundamental for female reproductive physiology. The major hypothesis is that folic acid supplementation will reduce the incidence of oocyte aneuploidy associated with advanced maternal aging. Here, I examined the effect of dietary folic acid supplementation on maternal age-induced oocyte aneuploidy using Bub1-heterozygous mice, a transgenic mouse model of aging-associated oocyte aneuploidy. Results showed that old female mice (24 weeks on a diet) fed a folic acid supplemented diet (8 mg/kg) had significantly more (2-fold) normal oocytes compared to the control group (2 mg/kg). Second, I examined the effect of dietary folic acid deficiency, adequacy and supplementation on colchicine-induced oocyte aneuploidy, as a model for studying age- induced oocyte aneuploidy. Results showed that colchicine treatment arrested a high proportion of oocytes (68%) in meiosis I leaving only 32% of meiosis II oocytes for analysis. No differences among the diet groups were observed. These preliminary results indicate that a larger sample size of mice would be required to determine whether diet has an effect on colchicne-induced oocyte aneuploidy and/or the use of a lower colchcine dose or mouse strain may prove more efficient. My data suggest that folic acid supplementation might mitigate the effect of aging on oocyte aneuploidy and that folate may play a causal role in the development of oocyte aneuploidies. These data, if replicated, suggest that women, especially older women, may benefit from consuming a folic acid supplement in the pre-conception period to avoid aneuploidy-affected pregnancies such as miscarriage and trisomy syndromes.