Figure 1.

Proposal of an “epigenetic vicious circle” of maternal nutrition and its implication for bone health in offspring. Maternal malnutrition during pregnancy and lactation, including calcium or vitamin D deficiency or protein restriction, can epigenetically regulate gene expressions related with maternal vitamin D status and placental calcium transfer, and the hypothalamic-pituitary-adrenal (HPA) axis. Maternal stress is known to influence the developing HPA axis in the fetus. Thus, epidemiological studies have demonstrated an inverse association between birth weight and fasting plasma cortisol. Indices of the circulating cortisol profile in adult life have also been shown to influence bone density and rates of bone loss. Finally, it can impair bone health in offspring, including low BMD and osteoporosis. If female offspring affected in that way enter reproductive age and become pregnant, they expose their offspring in a similar way to a malnutrition perinatal environment that they were exposed to themselves, thereby closing an epigenetic “vicious intergenerative circle.” BMD: bone mineral density. (A color version of this figure is available in the online journal.)