Prenatal Programming of Human Neurological Function

Abstract

The human placenta expresses the genes for proopiomelanocortin and the major stress hormone, corticotropin-releasing hormone (CRH), profoundly altering the “fight or flight” stress system in mother and fetus. As pregnancy progresses, the levels of these stress hormones, including maternal cortisol, increase dramatically. These endocrine changes are important for fetal maturation, but if the levels are altered (e.g., in response to stress), they influence (program) the fetal nervous system with long-term consequences. The evidence indicates that fetal exposure to elevated levels of stress hormones (i) delays fetal nervous system maturation, (ii) restricts the neuromuscular development and alters the stress response of the neonate, (iii) impairs mental development and increases fearful behavior in the infant, and (iv) may result in diminished gray matter volume in children. The studies reviewed indicate that fetal exposure to stress peptides and hormones exerts profound programming influences on the nervous system and may increase the risk for emotional and cognitive impairment.

Maternal cortisol over the course of pregnancy and subsequent child amygdala and hippocampus volumes and affective problems

“…Sex. Because many animal and human studies suggest that fetal/child sex may moderate the effects of pre-or postnatal exposures on developmental outcomes (62,63,94), we included an interaction term between maternal prenatal cortisol and sex of the child in all our statistical models (SI Materials and Methods provides further details).…”

PlacentalHTR2Amethylation is associated with infant neurobehavioral outcomes

“…1 In a short window of time during early prenatal development, neural networks are formed and behavioral pathways are programmed, and this programming is vulnerable to environmental influences. 2 Environmental factors, including maternal stress, mood, and lifestyle, have been linked to altered neurodevelopmental programming and later life behavioral and neurologic outcomes, 3,4 but the molecular mechanisms underlying these relationships remain unclear.…”

Glucocorticoids: Biochemical Group That Play Key Role in Fetal Programming of Adult Disease

“…However, the placenta secretes placental corticotrophin releasing hormone (P-CRH) which is the major, if not the only, mean of cross talk between maternal and fetal HPA axis. As mentioned earlier (Section 1.2.2) that maternal cortisol is exerting negative feedback inhibition on her hypothalamus release of CRH, on contrast, it induces P-CRH secretion as pregnancy advances (76) which in turn will increase maternal and fetal adrenal cortisol secretion (77,78).…”