Fig. 1.

Schematic representing the proposed interaction between maternal, placental and fetal factors that may underlie aspects of programing of neurodevelopmental disease. Both maternal stress and immune activation have been associated with altered fetal programing of the developing hypothalamic–pituitary axis (HPA) and nervous system. Putative maternal contributions include increased glucocorticoids, pro-inflammatory cytokines, altered nutrient availability and dysregulated leptin and insulin signaling. In eutherian mammals, these maternal contributions are transmitted to the fetal compartment via the placenta. This transmission is achieved through passive permeability (i.e. glucocorticoids), active transport (e.g. glucose and other nutrients) and perhaps most intriguingly through endocrine and paracrine signaling within the endocrine placenta (e.g. glucocorticoid inactivation via 11-beta hydroxysteroid dehydrogenase 2 [11βHSD2] and local production of cytokines and growth factors). The resulting fetal hormonal milieu as transmitted via the placenta directly interacts with the developing embryo to shape the ontogenetic trajectory. Changes in programing are likely affected by developmental differences as well as embryo sex, which leads to chromosomal and somatic differences in both the placenta and embryo.