Prenatal programming of stress responsiveness and behaviours: Progress and perspectives

Abstract

Parental exposure to stress or glucocorticoids either before or during pregnancy can have profound influences on neurodevelopment, neuroendocrine function and behaviours in offspring. Specific outcomes are dependent on the nature, intensity and timing of the exposure, as well as species, sex and age of the subject. Most recently, it has become evident that outcomes are not confined to first‐generation offspring and that there may be intergenerational and transgenerational transmission of effects. There has been intense focus on the mechanisms by which such early exposure leads to long‐term and potential transgenerational outcomes, and there is strong emerging evidence that epigenetic processes (histone modifications, DNA methylation, and small non‐coding RNAs) are involved. New knowledge in this area may allow the development of interventions that can prevent, ameliorate or reverse the long‐term negative outcomes associated with exposure to early adversity. This review will focus on the latest research, bridging human and pre‐clinical studies, and will highlight some of the limitations, challenges and gaps that exist in the field.

Developmental programming of the HPA axis and related behaviours: epigenetic mechanisms

“…Mechanistic studies in animals are linking early exposures to adversity with changes in gene regulatory mechanisms, including modifications of DNA methylation and altered levels of miRNA (Chan et al 2018, McGowan & Matthews 2018. Similar associations are emerging from recent human studies (Sasaki et al 2013, Hamada & Matthews 2019. Several genes associated with the regulation of HPA function and related behaviours are susceptible to altered epigenetic modulation.…”

“…Prenatal exposure to sGC has been shown to influence HPA and stress-related behaviours in offspring in a number of animal models, including primates, sheep, guinea pigs, rats and mice (Moisiadis & Matthews 2014, McGowan & Matthews 2018, Hamada & Matthews 2019. Studies from our group in the guinea pig have shown that single and repeated in utero exposure to sGC results in increased HPA responsiveness to a novel environment in juvenile offspring, with no effect on basal cortisol levels (Moisiadis et al 2017(Moisiadis et al , 2018.…”

“…Outcomes are also very much dependent on the nature of the stressor, the timing and duration of exposure and the sex of the offspring. In addition, effects are dynamic such that phenotypes can differ depending on the age of the offspring at the time of assessment, and in females, the stage of the reproductive cycle (Hamada & Matthews 2019). In humans, maternal psychosocial stress and increased maternal cortisol through the first and second trimester were linked to elevated adrenocortical responses to stress in newborns and at 5 years of age (Davis et al 2011).…”

“…The early environment of the embryo, foetus and newborn have been clearly linked to altered hypothalamicpituitary-adrenal (HPA) function and related behaviours through the juvenile period and into adulthood (for reviews see Moisiadis & Matthews 2014, Chan et al 2018, McGowan & Matthews 2018, Hamada & Matthews 2019.…”

Early Life Adversities and Well-being Later in Life: Evidence from China

“…It has been shown that the gene expression and the DNA-methylation processes of babies are altered to adapt to the changing intrauterine environment. The methylation process of the genes such as Nr3c1, CRH, CRHBP, Crb,and Nr3c1 F1 promoter (see, e.g., Welberg & Seckl, 2001;Hamada & Matthews, 2019;McGowan & Matthews, 2017) would be altered. For instance, the Nr3c1 gene which controls the glucocorticoids receptor production and controls the HPA axis reactivity of babies.…”