The stress response normally results in the release of glucorticoid hormones that are secreted by the adrenal glands to enable several physiological functions. However, chronic stress leads to continual release of these hormones that are associated with serious mental and physical health problems.
Recent data show that environmental factors such as stress and toxins, for example pesticides and smoking, during prenatal and/or early life are known to result in adverse health effects not only in offspring but also in subsequent generations via epigenetics. These important studies are summarized below.
Effect of stress on early life, genetics and during conflict
The impact of stress on chronic non-communicable disorders, including common mental health disorders like depression, is discussed by George Chrousos in a video Q & A published in BMC Medicine. He highlights the physiological and economic factors that affect stress, as well as how it can be prevented and emphasizes the long term effects of stress in prenatal and early life by saying that:
“Prenatal and early life, (especially the first five years of life), are extremely vulnerable periods and that is why they are called critical or critically vulnerable periods. If there is stress during this time the stress hormones leave behind an epigenetic imprint, which accompanies the child for the rest of his or her life into adulthood and old age.”
There are several studies on the genetics of depression. The latest meta-analysis by Rudolf Uher and colleagues suggests the brain-derived neurotrophic factor (BDNF) Val66Met genetic polymorphism interacts more strongly with life stress than childhood adversity in depression. Even the authors of this analysis admit that most studies utilized self-report questionnaires which are subject to recall bias, and more robust methods are required to measure life stress such as interviews or use of social services records.
Posttraumatic stress disorder (PTSD) is one of the devastating effects of stress during war and conflict situations and a study shows paternal and maternal PSTD have differential epigenetic effects on the offspring of holocaust survivors. These survivors are vulnerable to anxiety and depression that is passed down from their parents which are mediated via epigenetics and not genetic transmission.
Jonathan Wells and colleagues additionally discuss how exposure to violence, mental health stressors, infection and malnutrition during war have intergenerational effects on health, and suggest long-term interventions are required in post-conflict situations.
Exposure from prenatal stress and environmental toxins
There are a number of studies that have determined the effects of stress across generations in general. A recent study by Gerlinde Metz and colleagues is the first to show that prenatal stress across generations in rats leads to reduced gestational length, poor pregnancy outcomes and epigenetic changes in somatic cells, suggesting a family history of stress could be linked to preterm birth and pregnancy outcomes in humans.
“The concept that ancestral stress, particularly during gestation, may influence disease etiology for generations to come is an important aspect to consider in regards to our environment and society. This is a novel concept that will need to be seriously considered in our future health management and therapy.”
Moving onto environmental toxicants like pesticides evidence from Michael Skinner’s own laboratory shows exposure of female rats to dichlorodiphenyltrichloroethane (DDT) promotes obesity and associated epigenetic changes three generations later, suggesting that some cases of obesity may be partly due to environmentally induced transgenerational inheritance.
Interestingly obesity in fathers is associated with a decrease in methylation of the insulin-like growth factor 2 gene in their newborns as observed in a study by Cathrine Hoyo and colleagues. The findings suggest that paternal obesity may disrupt normal imprinting in germ cells and affect the health of their offspring.
With regard to nicotine exposure during pregnancy a ground breaking preclinical study by Virender Rehan and colleagues shows nicotine exposure induces asthma in offspring, and the effects are permanently transmitted to subsequent generations via epigenetic changes in germ cells, providing a breakthrough in studying multigenerational effects of toxins. In light of these findings Frances Leslie discusses the importance of effective smoking cessation strategies during pregnancy. She says,
“Preclinical investigators have long argued that nicotine is a developmental teratogen and should not be used as a treatment for pregnant smokers [2,11]. The current finding of multigenerational effects of in utero nicotine exposure will provide critical support for this view.”
Overall, the evidence and discussions highlight that that prenatal and early life periods are influenced by stress and environmental toxins which result in unhealthy outcomes in the offspring and subsequent generations. Additionally, ancestral stress associated with war and conflict situations lead to traumatic effects over generations. In general the effects of exposure to stress and toxins observed across generations are mediated via epigenetic mechanisms and thus emphasis should be placed on the environment in our society to enable management and treatment of health outcomes.
The articles on the effects of stress and environmental toxins across generations have been published in BMC Medicine and these can be viewed at https://www.biomedcentral.com/bmcmed/tags/generation
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