Fetal and Neonatal HPA Axis.

Stress is an integral part of life. Activation of the hypothalamus-pituitary-adrenal (HPA) axis in the adult can be viewed as mostly adaptive to restore homeostasis in the short term. When stress occurs during development, and specifically during periods of vulnerability in maturing systems, it can significantly reprogram function, leading to pathologies in the adult. Thus, it is critical to understand how the HPA axis is regulated during developmental periods and what are the factors contributing to shape its activity and reactivity to environmental stressors. The HPA axis is not a passive system. It can actively participate in critical physiological regulation, inducing parturition in the sheep for instance or being a center stage actor in the preparation of the fetus to aerobic life (lung maturation). It is also a major player in orchestrating mental function, metabolic, and cardiovascular function often reprogrammed by stressors even prior to conception through epigenetic modifications of gametes. In this review, we review the ontogeny of the HPA axis with an emphasis on two species that have been widely studied-sheep and rodents-because they each share many similar regulatory mechanism applicable to our understanding of the human HPA axis. The studies discussed in this review should ultimately inform us about windows of susceptibility in the developing brain and the crucial importance of early preconception, prenatal, and postnatal interventions designed to improve parental competence and offspring outcome. Only through informed studies will our public health system be able to curb the expansion of many stress-related or stress-induced pathologies and forge a better future for upcoming generations.