Prenatal stress and later metabolic consequences: Systematic review and meta-analysis in rodents

Abstract

Background: Numerous rodent studies have evaluated the effects of maternal stress (MS) on later in life susceptibility to Metabolic Syndrome (MetS) intermediate phenotypes with varying results. The aim of this study was to quantitatively synthesize the available data on the effects of MS on offspring obesity, estimated indirectly by body mass (BM), body fat (BF) and plasma leptin; systolic blood pressure (SBP); plasma glucose (and insulin) and blood lipid concentrations. Methods: Literature was screened and summary estimates of the effect of MS outcomes were calculated by using random-effects models. Data on the effects of exogenous corticosteroid administration (or inhibition of 11β-HSD2) during pregnancy in rodents was analysed separately to characterize the direct phenotypic effects of prenatal corticosteroid excess (PCE). Results: We conducted 14 separate meta-analyses and synthesized relevant data on outcomes scarcely reported in literature. Both MS and PCE were associated with low birth weight without rapid catch-up growth resulting in decreased body mass later in life. Our analysis also revealed significant and contradictory effects on offspring adiposity. Little evidence was found for effects on glucose metabolism and blood lipids. We identified increased SBP in offspring exposed to PCE; however, there is not enough data to draw any conclusion about effects of MS on SBP. Conclusions: Neonatal weight proved to be decreased in offspring prenatally exposed to stress or corticosteroids, but laboratory rodents in the absence of a challenging environment did not show catch-up growth. The available evidence is inconclusive regarding the effect on adiposity revealing clear methodological and knowledge gaps. This meta-analysis also confirmed a significant positive association between PCE and SBP. Nevertheless, additional studies should address the association with MS.

Influence of prenatal stress on metabolic abnormalities induced by postnatal intake of a high-fat diet in BALB/c mice

“…49 Restraint stress would modify maternal behavior contributing to the long-term effects observed in offspring. 50 However, in a recent meta-analysis, we demonstrated that cross-fostering to non-stressed dams had the same effects on body weight than continuing with the same stressed mother, 24 suggesting that maternal stress does not influence body weight of these animals.…”

“…23 In this regard, in a recent meta-analysis of rodent studies, we found that birth weight was decreased in offspring exposed to PS, but then in the absence of a challenging environment, catch-up growth is prevented. 24 Sex is an important variable that seems to confer a differential vulnerability to stress. Men and women differ in physiological and behavioral responses to stressors and the epidemiological patterns of stress-related diseases.…”

Impact of maternal physical exercise on inflammatory and hypothalamic–pituitary–adrenal axis markers in the brain and lungs of prenatally stressed neonatal mice

“…Furthermore, physical exercise before and during the gestational period was able to reverse some of these effects, particularly in the hippocampus and lungs of females at day 10 of life. Available evidence indicates that prenatal stress can generate several deleterious effects, including an increase in inflammatory cytokines, hyperactivation of the HPA axis, an increase in glucocorticoid exposure, and reduction in GR and MR receptors, in addition to behavioral effects leading to the development of anxiety and depression (Burgueno et al., 2020; Harris & Glucocorticoids, 2011; Rakers et al., 2020). On the other hand, the effects of prenatal stress are still poorly explored in peripheral organs, such as the lungs, and at early ages, especially during the neonatal period.…”

“…A previous study from our group showed that prenatal stress may reduce the impact of asthma in adult mice (Vargas et al., 2016). On the other hand, evidence in the literature demonstrates that gestational stress is related to an increased risk of developing asthma and other diseases, including mental disorders and morphological and structural alterations in the hippocampus (Burgueno et al., 2020; Turcotte‐Tremblay et al., 2014). Nevertheless, the results presented here indicate beneficial effects of maternal treadmill exercise on inflammatory markers in the brain of prenatally stressed mice, corroborating a previous study in which exercise has been shown beneficial by helping to prevent the effects caused by stress in adult mice (Luft et al., 2020).…”

Changes Induced by Mind–Body Intervention Including Epigenetic Marks and Its Effects on Diabetes

“…Maternal antenatal stress has also been noted to affect body weight and glucose metabolism in the offspring [16]. According to a meta-analysis, body mass index (BMI) (18 studies) and body fat (5 studies) were significantly higher when under fetal stress [17]. In the placenta, HSD11B2 exists to reduce exposure to the maternal glucocorticoid hormone, converting cortisol or corticosterone into inactive metabolites.…”