Implication of sperm RNAs in transgenerational inheritance of the effects of early trauma in mice
Prof. Dr. Isabelle Mansuy, University Zürich, neuroscientist,
Submitted rat babies for the first 2 weeks after their birth to stress. The animas developed depression and anxiety disorders later in life. These children were then treated with love and caring and so was their offspring. However, the next 3 generations – as far us the study went – developed the same disorders. Mansury could show that these changes were passed on epigenetically, not genetically . Important genes of the fathers were incorrectly methylated, also several genes in eggs and sperm cells of the offspring
New scientific research suggests that the negative effects of trauma can be inherited. Fathers may actually transfer the consequences of their early experiences to their children via an epigenetic process. Researchers report that mice that experienced stress early on passed down the negative consequences – depression, underestimation of risk, and upset of metabolism – to their offspring, even if their offspring were not directly exposed to stress or trauma.
In a recent study, Isabelle Mansuy and her colleagues at the University of Zurich, Switzerland periodically removed mother mice from their babies, engaging the mothers in traumatic situations by physically restraining them or placing them in cold water in order to induce stress. Because the mothers were removed from their pups at random times every day, the mothers couldn’t nurture their babies in preparation for these traumatic experiences and, as a result, the pups grew up displaying depressive symptoms. This was expected. …
This research is also putting attention on the father and his epigenome, showing that behavioral changes as a result of trauma experienced by the father can indeed be inherited in mice. What is perhaps most fascinating is the potential to find similar biomarkers in humans. This could give us the ability to determine if increases in, for example, a certain type of microRNA can predict whether someone may suffer from stress or develop psychiatric disorders later in life.
Affectionate Moms with Depression May Epigenetically Buffer Their Child from Stress
Different environmental factors experienced by a child can undoubtedly impact their life in the long run. Whether they were born into poverty, lack access to education, or are surrounded by violence, these experiences have the ability to dramatically disrupt their lives if they’re without the right support system. But, could a mother’s exposure to stress impact her child even before he or she is born? And could the way a mother treats her child buffer any adverse impact? Research on depressed mothers has recently shown that their response to stress can be transferred through the placenta and negatively impact their baby developing in the womb, affecting birth weight, susceptibility to disease, and brain development. Now, researchers are expanding on this evidence and have uncovered an epigenetic connection between maternal depression, sensitivity, and the programming of a child’s stress response system.
In a study conducted at the University of Utah, led by Elisabeth Conradt, scientists looked at how a mother’s hormonal response to stress, exhibited by her neuroendocrine system, epigenetically affected her infant’s hormone release response to stress. This stress reaction in the child is guided by the hypothalamic-pituitary-adrenal (HPA) axis, which describes connections between the hypothalamus, the pituitary gland, and the adrenal glands. The well-known HPA axis creates a hormone known as cortisol, which is produced in reaction to stressful events.
Reference: Conradt, E., Hawes, K., Guerin, D., Armstrong, D.A., Marsit, C.J., Tronick, E., Lester, B.M. (2016). The Contributions of Maternal Sensitivity and Maternal Depressive Symptoms to Epigenetic Processes and Neuroendocrine Functioning. Child Development, 87 (1): 73.
Stressed mouse dads give their offspring high blood sugar
Mouse fathers under psychological stress were more likely to have offspring with high blood sugar compared to their unstressed counterparts. In a study appearing February 18 in Cell Metabolism, researchers link this difference to an epigenetic change in the stressed dad’s sperm–a change that they could prevent by blocking the father’s stress hormones. The study adds to growing evidence that a male’s life experience can be passed down through more than his genetic code alone.
Epigenetics and Obesity and Diabetes Epidemic?
A study was published March 14 in Nature Genetics and Importantly, the study serves as a demonstration that traits acquired by parents can be passed on to their children. Knowing that our behavior is programmed into our gametes may motivate both mom and dad to take even greater care of themselves before having children.
Reference: Huypens, P., Sass, S., Wu, M., Dyckhoff, D., Tschöp, M., Theis, F., Marschall, S., Hrabě de Angelis, M., Beckers, J. (2016). Epigenetic germline inheritance of diet-induced obesity and insulin resistance. Nature Genetics.
Could Stressed Fathers Epigenetically Give their Children High Blood Sugar?
What if stress experienced by fathers could actually be passed down epigenetically to their children, who then experience its effects later in life? Previous research has hinted that, in mice, trauma experienced by a father leaves epigenetic marks on his sperm RNA, which is inherited by his offspring who later express the same depressive behaviors as their dad. Also, another study that investigated the devastating Quebec Ice Storm of 1998 has suggested that prenatal maternal stress could trigger distinct DNA methylation signatures in ice storm babies. And now evidence for intergenerational epigenetic inheritance continues to mount as a new study links stress in mice fathers to increased high blood sugar in their offspring due to the epigenetic modification called DNA methylation. A group of researchers in China, including those from Shanghai Jiao Tong University School of Medicine, Rui-Jin Hospital, and Hubei Polytechnic University School of Medicine, recently published their supportive research in Cell Metabolism.
Reference: Wu, Lu, and Jiao et al. (2016). Paternal Psychological Stress Reprograms Hepatic Gluconeogenesis in Offspring. Cell Metabolism, In press.
Biological mechanism passes on long-term epigenetic ‘memories’
Tel Aviv University researchers discover the on/off button for inheriting responses to environmental changes
According to epigenetics — the study of inheritable changes in gene expression not directly coded in our DNA — our life experiences may be passed on to our children and our children’s children. Studies on survivors of traumatic events have suggested that exposure to stress may indeed have lasting effects on subsequent generations. But how exactly are these genetic “memories” passed on?
A new Tel Aviv University study pinpoints the precise mechanism that turns the inheritance of environmental influences “on” and “off.” The research, published last week in Cell and led by Dr. Oded Rechavi and his group from TAU’s Faculty of Life Sciences and Sagol School of Neuroscience, reveals the rules that dictate which epigenetic responses will be inherited, and for how long.
“Until now, it has been assumed that a passive dilution or decay governs the inheritance of epigenetic responses,” Dr. Rechavi said. “But we showed that there is an active process that regulates epigenetic inheritance down through generations.”
Passing stress from one generation to the next
Researchers have been preoccupied with how the effects of stress, trauma, and other environmental exposures are passed from one generation to the next for years. Small RNA molecules — short sequences of RNA that regulate the expression of genes — are among the key factors involved in mediating this kind of inheritance. Dr. Rechavi and his team had previously identified a “small RNA inheritance” mechanism through which RNA molecules produced a response to the needs of specific cells and how they were regulated between generations.
“We previously showed that worms inherited small RNAs following the starvation and viral infections of their parents. These small RNAs helped prepare their offspring for similar hardships,” Dr. Rechavi said. “We also identified a mechanism that amplified heritable small RNAs across generations, so the response was not diluted. We found that enzymes called RdRPs are required for re-creating new small RNAs to keep the response going in subsequent generations.”
Most inheritable epigenetic responses in C.elegans worms were found to persist for only a few generations. This created the assumption that epigenetic effects simply “petered out” over time, through a process of dilution or decay.
“But this assumption ignored the possibility that this process doesn’t simply die out but is regulated instead,” said Dr. Rechavi, who in this study treated C.elegans worms with small RNAs that target the GFP (green fluorescent protein), a reporter gene commonly used in experiments. “By following heritable small RNAs that regulated GFP — that ‘silenced’ its expression — we revealed an active, tuneable inheritance mechanism that can be turned ‘on’ or ‘off.'”
The scientists discovered that specific genes, which they named “MOTEK” (Modified Transgenerational Epigenetic Kinetics), were involved in turning on and off epigenetic transmissions.
“We discovered how to manipulate the transgenerational duration of epigenetic inheritance in worms by switching ‘on’ and ‘off’ the small RNAs that worms use to regulate genes,” said Dr. Rechavi. “These switches are controlled by a feedback interaction between gene-regulating small RNAs, which are inheritable, and the MOTEK genes that are required to produce and transmit these small RNAs across generations.
“The feedback determines whether epigenetic memory will continue to the progeny or not, and how long each epigenetic response will last.”
A comprehensive theory of heredity?
Although their research was conducted on worms, the team believes that understanding the principles that control the inheritance of epigenetic information is crucial for constructing a comprehensive theory of heredity for all organisms, humans included.
“We are now planning to study the MOTEK genes to know exactly how these genes affect the duration of epigenetic effects,” said Leah Houri-Zeevi, a PhD student in Dr. Rechavi’s lab and first author of the paper. “Moreover, we are planning to examine whether similar mechanisms exist in humans.”
Eric J. Richards, Assistant Professor PH.D. Harvard University, 1989, Molecular Genetics and Plant Biology Programs
Could show that the way rat babies were treated by their moms and caretakers, determined. If and how a certain receptor on the hippocampus is methylated. Positive experiences permanently activated this receptor, a single negative experience was enough to permanently disable the receptor. This setting was passed on to the following generations.
A recent study in the Netherlands on women who gave birth to children in the time just after the WW II (hunger, poverty, illness), revealed, that their daughters had twice the rate of schizophrenia as the control group. The researchers could show that changes on the epigenetic controls of several genes responsible for development and growth were responsible.
Eva Lablanka and Gal Razz (University of Tel Aviv demonstrated that chemical toxins, which affect the aspects of the hormonal system responsible for reproduction, lead to permanent changes are passed on epigenetically to their offspring, generations after generation after after generation, until this family line dies out.
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