Maternal influences on epigenetic programming of the developing hypothalamic‐pituitary‐adrenal axis

Abstract

Parental and environmental factors during the prenatal and postnatal periods permanently affect the physiology and metabolism of offspring, potentially increasing disease risk later in life. Underlying mechanisms are being elucidated, and effects on a number of organs and metabolic pathways are likely involved. In this review, we consider effects on the developing hypothalamic-pituitary-adrenal (HPA) axis, which may represent a common pathway for developmental programming. The focus is on prenatal and early postnatal development, during which the HPA axis may be programmed in a manner that affects health for a lifetime. Programming of the HPA axis involves, at least in part, epigenetic remodeling of chromatin, leading to alterations in the expression of genes in many organs and tissues involved in HPA activation and response, including the hippocampus and peripheral tissues.

Early Life Trauma and Attachment: Immediate and Enduring Effects on Neurobehavioral and Stress Axis Development

“…Both animal and human research demonstrate that early life experiences interact with genetics to program the central nervous and endocrine systems, including the hypothalamus–pituitary–adrenal (HPA)-axis (1–5). Infant experiences typically occur within the context of the mother and the quality of caregiving by the mother, determined by the patterning and intensity of maternal stimulation of pups’ sensory systems, is a key regulator of HPA-axis neuroplasticity in the neonatal period (6–10).…”

Dietary restriction in the periconceptional period in normal-weight or obese ewes results in increased abundance of angiotensin-converting enzyme (ACE) and angiotensin type 1 receptor (AT1R) in the absence of changes in ACE or AT1R methylation in the adrenal of the offspring

“…Adversity in early life can result in long-term changes in the HPA axis as a consequence of epigenetic modifications of key regulatory genes in rodents, sheep and humans (Weaver et al 2004, Oberlander et al 2008, Murgatroyd et al 2009, Stevens et al 2010, Zhang et al 2010, Grace et al 2011. It has previously been demonstrated in sheep that exposure to maternal undernutrition during the periconceptional period and early gestation results in altered fetal adrenal development from as early as 55 days of gestation (termZ150G3 days of gestation; MacLaughlin et al 2007), an earlier prepartum activation of the fetal HPA axis (Edwards & McMillen 2002b, Bloomfield et al 2004, an increased risk of premature delivery (Bloomfield et al 2003) and increased plasma cortisol concentrations in the post-natal lamb (Gardner et al 2006, Chadio et al 2007.…”

Effects of oxytocin used during delivery on development: A retrospective cohort study

“…It is known that some obstetric variables related to delivery influence the incidence of maternal mood disorders during the postpartum period (Blom et al, 2010), and, on the other hand, in vitro manipulation of the oxytocin-receptor system causes dysfunctions in generation of maternal-offspring bonds in animals (Curley, Jensen, Franks, & Champagne, 2012;Grace, Kim, & Rogers, 2011). Since both aspects are modulated by endogenous oxytocin and have great importance for subsequent development of the newborn, exogenous oxytocin administered during the dilatation or expulsion periods may, at least theoretically, epigenetically modulate expression of genes encoding for oxytocin receptor synthesis (Borrow & Cameron, 2012;Dahlen et al, 2013).…”