Transfer of maternal psychosocial stress to the fetus

Psychosocial maternal stress experienced during different vulnerable periods throughout gestation is thought to increase the individual's risk to develop neuropsychiatric, cardiovascular and metabolic disease in later life. Cortisol has generally been identified as the major mediator of maternal stress transfer to the fetus. Its lipophilic nature allows a trans-placental passage and thus excessive maternal cortisol could persistently impair the development of the fetal hypothalamic-pituitary-adrenal axis (HPAA). However, cortisol alone cannot fully explain all effects of maternal stress especially during early to mid pregnancy before maturation of the fetal HPAA has even begun and expression of fetal glucocorticoid receptors is limited. This review focuses on mediators of maternal fetal stress transfer that in addition to cortisol have been proposed as transmitters of maternal stress: catecholamines, cytokines, serotonin/tryptophan, reactive-oxygen-species and the maternal microbiota. We propose that the effects of psychosocial maternal stress on fetal development and health and disease in later life are not a consequence of a single pathway but are mediated by multiple stress-transfer mechanisms acting together in a synergistic manner.