Prenatal Social Stress in the Rat Programmes Neuroendocrine and Behavioural Responses to Stress in the Adult Offspring: Sex‐Specific Effects

Abstract

Stress exposure during pregnancy can 'programme' adult behaviour and hypothalamic-pituitary-adrenal (HPA) axis stress responsiveness. In the present study, we utilised an ethologically relevant social stressor to model the type of stress that pregnant women may experience. We investigated the effects of social defeat by a resident lactating rat over 5 days during the last week of pregnancy on the pregnant intruder rat HPA axis, and on HPA responsivity to stress and anxiety-related behaviour in the adult offspring of the socially-defeated intruder rats. HPA axis responses after social defeat were attenuated in the pregnant rats compared to virgin females. In the adult offspring, systemic interleukin (IL)-1beta or restraint increased adrenocorticotrophic hormone and corticosterone secretion in male and female control rats; however, in prenatally stressed (PNS) offspring, HPA responses were greatly enhanced and peak hormone responses to IL-1beta were greater in females versus males. Male PNS rats displayed increased anxiety behaviour on the elevated plus maze; however, despite marked changes in anxiety behaviour across the oestrous cycle, there were no differences between female control and PNS rats. Investigation of possible mechanisms showed mineralocorticoid mRNA levels were reduced in the hippocampus of male and female PNS offspring, whereas glucocorticoid receptor mRNA expression was modestly reduced in the CA2 hippocampal subfield in female PNS rats only. Corticotropin-releasing hormone mRNA and glucocorticoid receptor mRNA expression in the central amygdala was greater in PNS males and females compared to controls. The data obtained in the present study indicate that prenatal social stress differentially programmes anxiety behaviour and HPA axis responses to stress in male and female offspring. Attenuated glucocorticoid feedback mechanisms in the limbic system may underlie HPA axis hyper-reactivity to stress in PNS offspring.

Error management theory and the adaptive significance of transgenerational maternal‐stress effects on offspring phenotype

“…Our perspective may also provide insights into determining the origin of sex‐specific sensitivity to maternal or developmental stress (Box 3; Bale & Epperson, 2015; Brunton & Russell, 2010; Love et al., 2005). In species where there is disparity in the proximate or ultimate costs of raising a given sex, our framework predicts that the more expensive sex would have a lower threshold to respond to maternal stress given that the costs of errors would be higher compared to the less expensive sex (Love & Williams, 2008; Love et al., 2005).…”

The Placenta as a Mediator of Stress Effects on Neurodevelopmental Reprogramming

“…In nonhuman primates, chronic maternal stress leads to deficits in attention, object permanence, and motor function in offspring, in particular when the stress was experienced early in gestation (Schneider and Coe, 1993;Schneider, 1992;Schneider et al, 1999). In rodent models, prenatal stress induces hypothalamic-pituitary-adrenal (HPA) stress axis dysregulation, heightened behavioral stress reactivity, depression-like behaviors, and cognitive deficits (Bock et al, 2015;Brunton and Russell, 2010;Cottrell and Seckl, 2009;Darnaudéry and Maccari, 2008;Kapoor and Matthews, 2005;Kapoor et al, 2009;Lemaire et al, 2000;Bale, 2007, 2008;Weinstock, 2008). Similar to human studies, the gestational timing of the stress and fetal sex are key determinants in offspring outcome, where studies in both mice and guinea pigs found that prenatal stress produced HPA axis dysregulation and cognitive effects only in male offspring exposed during early or mid-gestation Matthews, 2005, 2008;Kapoor et al, 2009;Bale, 2007, 2008).…”

Using Chronic Social Stress to Model Postpartum Depression in Lactating Rodents

“…Recent rodent studies have been focusing on the use of ethologically relevant stressors, such as chronic social stress (CSS), in the study of the effects of stress on offspring behavior and mood disorders [9][10][11][12][13] . In an effort to develop an ethological model for postpartum depression, reduce the physiological component of the stressor used, and generate consistent behavioral and physiological results, our lab has focused on the use of social stress.…”