Sex dependent impact of gestational stress on predisposition to eating disorders and metabolic disease

Abstract

ObjectiveVulnerability to eating disorders (EDs) is broadly assumed to be associated with early life stress. However, a careful examination of the literature shows that susceptibility to EDs may depend on the type, severity and timing of the stressor and the sex of the individual. We aimed at exploring the link between chronic prenatal stress and predisposition to EDs and metabolic disease.MethodsWe used a chronic variable stress protocol during gestation to explore the metabolic response of male and female offspring to food restriction (FR), activity-based anorexia (ABA), binge eating (BE) and exposure to high fat (HF) diet.ResultsContrary to controls, prenatally stressed (PNS) female offspring showed resistance to ABA and BE and displayed a lower metabolic rate leading to hyperadiposity and obesity on HF diet. Male PNS offspring showed healthy responses to FR and ABA, increased propensity to binge and improved coping with HF compared to controls. We found that long-lasting abnormal responses to metabolic challenge are linked to fetal programming and adult hypothalamic dysregulation in PNS females, resulting from sexually dimorphic adaptations in placental methylation and gene expression.ConclusionsOur results show that maternal stress may have variable and even opposing effects on ED risk, depending on the ED and the sex of the offspring.

Beyond the Activity-Based Anorexia Model: Reinforcing Values of Exercise and Feeding Examined in Stressed Adolescent Male and Female Mice

“…If so, it is expected that AN precipitating factors, such as perinatal and postnatal trauma (see Introduction), amplify such an imbalance. Actually, the use of prenatal stress, early weaning or repeated maternal separation has indicated that ABA symptomatology might be exacerbated by these procedures, albeit not necessarily in a sex-dependent manner (Glavin and Pare, 1985; Hancock and Grant, 2009; Schroeder et al, 2018). In the present study, we selected PWIR as the infant trauma.…”

“…As opposed to genetics, sex, and age, available data on the impact of early traumatic stimuli in the ABA paradigm are somewhat scarce. Prenatal stress (Boersma et al, 2016; Schroeder et al, 2018), early weaning (Glavin and Pare, 1985) or postnatal separation (Carrera et al, 2009; Hancock and Grant, 2009) have shown diverse effects, including when considering the animal sex. Although these studies addressed the consequences of prenatal and perinatal stress manipulations that might bear translational value with respect to AN, the question of the impact of stress during childhood and early adolescence should be considered.…”

A Framework for Developing Translationally Relevant Animal Models of Stress-Induced Changes in Eating Behavior

“…In rodent models, although stress is often linked to the consumption of "comfort foods" (90,91), this is not the case for all stressors. For example, in males, social isolation (92,93) and chronic mild stress (94-98) can decrease intake of sucrose.…”

“…Exposure to stress across the lifespan can impact the outcome of the response on food intake in a sex-, age-and diet-dependent manner, in both humans (reviewed in ( 128)), and rodents (44,45,91,127,(129)(130)(131)(132). In rodents, stress exposure throughout gestation does not affect baseline food intake in males (91,129), but decreases baseline intake in females (91), and reduces sucrose preference in both sexes (129,132). Combining stress exposures in two developmental periods can produce synergistic effects.…”

The role of TET proteins in stress-induced neuroepigenetic and behavioural adaptations

“…Prenatal stress-induced or genetic reductions in placental OGT result in transcriptional and epigenetic regulation in placental tissue and the embryonic HYP associated with maladaptive stress responses in adulthood in a sex-specific manner ( Howerton et al, 2013 ; Howerton and Bale, 2014 ). Moreover, work from our own lab suggests that modulation of Tet and Dnmt mRNA levels are modulated in a sex-specific manner within placental tissue following prenatal stress in mice ( Schroeder et al, 2018 ). Thus, considering the widespread epigenetic and transcriptional changes upon placental OGT perturbations, the abundant expression of TET proteins within the placenta ( Yosefzon et al, 2017 ) and stress-sensitivity of TETs in placental tissue, it is likely that TET-OGT interactions play a role in the response of placental tissue and thus subsequent developmental trajectories following prenatal stress exposure.…”