Fetal Programming by Methyl Donor Deficiency Produces Pathological Remodeling of the Ascending Aorta.

[Figure: see text].

Methyl donor deficiency impairs bone development via peroxisome proliferator-activated receptor-γ coactivator-1α-dependent vitamin D receptor pathway.

Deficiency in methyl donor (folate and vitamin B) and in vitamin D is independently associated with altered bone development. Previously, methyl donor deficiency (MDD) was shown to weaken the activity of nuclear receptor coactivator, peroxisome proliferator-activated receptor-γ coactivator-1α (PGC1α), for nuclear signaling in rat pups, including estrogen receptor-α and estrogen-related receptor-α; its effect on vitamin D receptor (VDR) signaling, however, is unknown. We studied bone development under MDD in rat pups and used human MG-63 preosteoblast cells to better understand the associated molecular mechanism.