Commentary

Effects of Maternal Prenatal Stress on the Fetal Brain and Hope for the Prevention of Psychopathology

Numerous clinical and animal studies have found that antenatal chronic stress can lead to pathological changes the hippocampal development from embryos to adult, but the mechanisms are not well understood. Proteomic analyses provide a new insight to explore the potential mechanisms of this impairment. In this study, gestating rats were subjected to chronic unpredictable mild stress (CUMS) during pregnant days using nine different stimulations, and the changes of the learning and memory performance and the expression of proteins in the hippocampus of offspring were measured. It was found that prenatal chronic stress led to growth retardation, impaired spatial learning and memory ability in the offspring. Furthermore, prenatal stress caused various degrees of damage to neurons, Nissl body, mitochondria and synaptic structures in hippocampal CA3 region of offspring. In addition, 26 significantly different expressed proteins (DEPs) were found between the two groups by using isoquantitative tag-based relative and absolute quantification (iTRAQ) proteomics analysis. Further analyses of these DEPs showed that involved with different molecular functions and several biological processes, such as biological regulation and metabolic processes. Among these, the KEGG pathway enrichment showed that learning and memory impairment was mainly associated with the cyclic guanosine monophosphate protein kinase G (cGMP-PKG) pathway. At the same time, compared with OPC group, the NO, nNOS and cGMP level were significantly decreased, and the expression of PKG protein was also dropped. All of these results suggested that pregnant rats exposed to chronic psychological stress might impair spatial learning and memory ability of offspring, by disturbing the NO/cGMP/PKG signaling pathway.

Stress reactivity is a core aspect of temperament, reflecting a biologically based, socially shaped, tendency to distress that may have intergenerational origins. One commonly held view is that stress exposures in utero and postpartum may prime offspring to anticipate harsh future conditions, triggering a biologically programmed predictive adaptive sensitivity to threat. However, emerging evidence suggests that stress reactivity in offspring is also associated with both maternal and paternal trauma and mental health difficulties that occur well before offspring conception. This positions the developmental origins of stress reactivity within a longer-term intergenerational life-course perspective. We propose there is significant potential for advancing knowledge in this area using multidisciplinary approaches including new methods and data sources.

Stress is conceived as any internal or external stimulus capable of altering/disrupting the physiological milieu, and the ability to cope with such aversive situations is a crucial determinant of health and disease. Various kinds of stress and their impact on the biological system have been investigated for many years. This “stress response” is a highly interactive phenomenon, which involves complex relationships between the HPA axis and other neuroendocrine systems that affect several aspects of social behavior. Stressful experiences in early gestation are better predictors of adverse outcomes than the same measures assessed later in gestation. It is now clear that varieties of stressful conditions during pregnancy can have long-lasting effects on fetal development with respect to emotional, behavioral, immune, and cognitive outcomes. The stress has the potential for ‘social programming’ by differentially influencing reproductive behavior and fetal development. The role of epigenetic changes in mediating alterations in offspring outcome following prenatal stress is likely to be important and starting to be explored. The chapter provides a framework from which novel investigations could work to understand the significance of exposure to stress during early life and its impact on later health, fitness, and social behaviors. The understanding may lead to devise strategies for positive effects on fitness following early life stress.