Not all in the genes: Are we inheriting more than we think?

A fundamental discovery about a driver of healthy development in embryos could rewrite our understanding of what can be inherited from our parents and how their life experiences may shape us.

The new research suggests that epigenetic information, which sits on top of DNA and is normally reset between generations, is more frequently carried from mother to offspring than previously thought.

The study, led by researchers from WEHI (Melbourne, Australia), significantly broadens our understanding of which genes have epigenetic information passed from mother to child and which proteins are important for controlling this unusual process.

Epigenetics is a rapidly growing field of science that investigates how our genes are switched on and off to allow one set of genetic instructions to create hundreds of different cell types in our body.

Epigenetic changes can be influenced by environmental variations such as our diet, but these changes do not alter DNA and are normally not passed from parent to offspring.

While a tiny group of 'imprinted' genes can carry epigenetic information across generations, until now, very few other genes have been shown to be influenced by the mother's epigenetic state.

The new research reveals that the supply of a specific protein in the mother's egg can affect the genes that drive skeletal patterning of offspring.

Chief investigator Professor Marnie Blewitt said the findings initially left the team surprised.

"It took us a while to process because our discovery was unexpected," Professor Blewitt, Joint Head of the Epigenetics and Development Division at WEHI, said.

"Knowing that epigenetic information from the mother can have effects with life-long consequences for body patterning is exciting, as it suggests this is happening far more than we ever thought.

"It could open a Pandora's box as to what other epigenetic information is being inherited."

The study, led by WEHI in collaboration with Associate Professor Edwina McGlinn from Monash University and The Australian Regenerative Medicine Institute, is published in Nature Communications.

The new research focused on the protein SMCHD1, an epigenetic regulator discovered by Professor Blewitt in 2008, and Hox genes, which are critical for normal skeletal development.

Hox genes control the identity of each vertebra during embryonic development in mammals, while the epigenetic regulator prevents these genes from being activated too soon.

In this study, the researchers discovered that the amount of SMCHD1 in the mother's egg affects the activity of Hox genes and influences the patterning of the embryo. Without maternal SMCHD1 in the egg, offspring were born with altered skeletal structures.

First author and PhD researcher Natalia Benetti said this was clear evidence that epigenetic information had been inherited from the mother, rather than just blueprint genetic information.

"While we have more than 20,000 genes in our genome, only that rare subset of about 150 imprinted genes and very few others have been shown to carry epigenetic information from one generation to another," Benetti said.

"Knowing this is also happening to a set of essential genes that have been evolutionarily conserved from flies through to humans is fascinating."

The research showed that SMCHD1 in the egg, which only persists for two days after conception, has a life-long impact.

Variants in SMCHD1 are linked to developmental disorder Bosma arhinia microphthalmia syndrome (BAMS) and facioscapulohumeral muscular dystrophy (FSHD), a form of muscular dystrophy. The researchers say their findings could have implications for women with SMCHD1 variants and their children in the future.

A drug discovery effort at WEHI is currently leveraging the SMCHD1 knowledge established by the team to design novel therapies to treat developmental disorders, such as Prader Willi Syndrome and the degenerative disorder FSHD.

Read more at Science Daily

Prehistoric mums may have cared for kids better than we thought

A new study from The Australian National University (ANU) has revealed the death rate of babies in ancient societies is not a reflection of poor healthcare, disease and other factors, but instead is an indication of the number of babies born in that era.

The findings shed new light on the history of our ancestors and debunk old assumptions that infant mortality rates were consistently high in ancient populations.

The study also opens up the possibility mothers from early human societies may have been much more capable of caring for their children than previously thought.

"It has long been assumed that if there are a lot of deceased babies in a burial sample, then infant mortality must have been high," lead author Dr Clare McFadden, from the ANU School of Archaeology and Anthropology, said.

"Many have assumed that infant mortality was very high in the past in the absence of modern healthcare.

"When we look at these burial samples, it actually tells us more about the number of babies that were born and tells us very little about the number of babies that were dying, which is counterintuitive to past perceptions."

The researchers examined United Nations (UN) data from the past decade for 97 countries that looked at infant mortality, fertility and the number of deaths that occurred during infancy. The analysis revealed that fertility had a much greater influence on the proportion of deceased infants than the infant mortality rate.

Because there is very little known about early human societies, the UN data helped the researchers make interpretations about humans from the past 10,000 years.

"Archaeology has often looked at the proportion of deceased infants to learn something about infant mortality. There was an assumption that nearly half, 40 per cent, of all babies born in prehistoric populations died within the first year of their lives," Dr McFadden said.

After analysing the UN data, Dr McFadden found no evidence to support this assumption.

"Burial samples show no proof that a lot of babies were dying, but they do tell us a lot of babies were being born," she said.

"If mothers during that time were having a lot of babies, then it seems reasonable to suggest they were capable of caring for their young children."

The ANU findings could help researchers understand more about humans that inhabited the Earth tens of thousands of years ago and in particular, how mothers in ancient societies cared for and interacted with their children.

Dr McFadden said as we piece together more clues about the history of humans, it's important we "bring some humanity" back to our ancestors.

"Artistic representations and popular culture tend to view our ancestors as these archaic and incapable people, and we forget their emotional experience and responses such as the desire to provide care and feelings of grief date back tens of thousands of years, so adding this emotional and empathetic aspect to the human narrative is really important," she said.

The researchers would also like to see greater emphasis placed on the stories of women in past populations, which they say have long been neglected in favour of male stories.

"We hear a lot of stories about conflict involving males and even narratives around colonisation and expansion of populations tend to have a focus on men and I think it's really important to be telling these stories of women in the past and what the female experience was like, including the roles they played in the community and as a mother," Dr McFadden said.

Read more at Science Daily

Stress on mothers can influence biology of future generations

A mother's response to stress can even influence her grandchildren.

Biologists at the University of Iowa found that roundworm mothers subjected to heat stress passed, under certain conditions and through modifications to their genes, the legacy of that stress exposure not only to their offspring but even to their offspring's children.

The researchers, led by Veena Prahlad, associate professor in the Department of Biology and the Aging Mind and Brain Initiative, looked at how a mother roundworm reacts when she senses danger, such as a change in temperature, which can be harmful or even fatal to the animal. In a study published last year, the biologists discovered the mother roundworm releases serotonin when she senses danger. The serotonin travels from her central nervous system to warn her unfertilized eggs, where the warning is stored, so to speak, and then passed to offspring after conception.

Examples of such genetic cascades abound, even in humans. Studies have shown that pregnant women affected by famine in the Netherlands from 1944 to 1945, known as the Dutch Hunger Winter, gave birth to children who were influenced by that episode as adults -- with higher rates than average of obesity, diabetes, and schizophrenia.

In this study, the biologists wanted to find out how the memory of stress exposure was stored in the egg cell.

"Genes have 'memories' of past environmental conditions that, in turn, affect their expression even after these conditions have changed," Prahlad explains. "How this 'memory' is established and how it persists past fertilization, embryogenesis, and after the embryo develops into adults is not clear. "This is because during embryogenesis, most organisms typically reset any changes that have been made to genes because of the genes' past activity."

Prahlad and her teams turned to the roundworm, a creature regularly studied by scientists, for clues. They exposed mother roundworms to unexpected stresses and found the stress memory was ingrained in the mother's eggs through the actions of a protein called the heat shock transcription factor, or HSF1. The HSF1 protein is present in all plants and animals and is activated by changes in temperature, salinity, and other stressors.

The team found that HSF1 recruits another protein, an enzyme called a histone 3 lysine 9 (H3K9) methyltransferase. The latter normally acts during embryogenesis to silence genes and erase the memory of their prior activity.

However, Prahald's team observed something else entirely.

"We found that HSF1 collaborates with the mechanisms that normally act to 'reset' the memory of gene expression during embryogenesis to, instead, establish this stress memory," Prahlad says.

One of these newly silenced genes encodes the insulin receptor, which is central to metabolic changes with diabetes in humans, and which, when silenced, alters an animal's physiology, metabolism, and stress resilience. Because these silencing marks persisted in offspring, their stress-response strategy was switched from one that depended on the ability to be highly responsive to stress, to relying instead on mechanisms that decreased stress responsiveness but provided long-term protection from stressful environments.

"What we found all the more remarkable was that if the mother was exposed to stress for a short period of time, only progeny that developed from her germ cells that were subjected to this stress in utero had this memory," Prahlad says. "The progeny of these progeny (the mother's grandchildren) had lost this memory. However, if the mother was subjected to a longer period of stress, the grandchildren generation retained this memory. Somehow the 'dose' of maternal stress exposure is recorded in the population."

The researchers plan to investigate these changes further. HSF1 is not only required for stress resistance but also increased levels of both HSF1 and the silencing mark are associated with cancer and metastasis. Because HSF1 exists in many organisms, its newly discovered interaction with H3K9 methyltransferase to drive gene silencing is likely to have larger repercussions.

Read more at Science Daily

New mothers’ sleep loss linked to accelerated aging

When new mothers complain that all those sleepless nights caring for their newborns are taking years off their life, they just might be right, UCLA research published this summer in the journal Sleep Health suggests.

Scientists studied 33 mothers during their pregnancies and the first year of their babies' lives, analyzing the women's DNA from blood samples to determine their "biological age," which can differ from chronological age. They found that a year after giving birth, the biological age of mothers who slept less than seven hours a night at the six-month mark was three to seven years older than those who logged seven hours or more.

Mothers who slept less than seven hours also had shorter telomeres in their white blood cells. These small pieces of DNA at the ends of chromosomes act as protective caps, like the plastic tips on the ends of shoelaces. Shortened telomeres have been linked to a higher risk of cancers, cardiovascular and other diseases, and earlier death.

"The early months of postpartum sleep deprivation could have a lasting effect on physical health," said the study's first author, Judith Carroll, UCLA's George F. Solomon Professor of Psychobiology. "We know from a large body of research that sleeping less than seven hours a night is detrimental to health and increases the risk of age-related diseases."

While participants' nightly sleep ranged from five to nine hours, more than half were getting less than seven hours, both six months and one year after giving birth, the researchers report.

"We found that with every hour of additional sleep, the mother's biological age was younger," said Carroll, a member of the Cousins Center for Psychoneuroimmunology at UCLA's Jane and Terry Semel Institute for Neuroscience and Human Behavior. "I, and many other sleep scientists, consider sleep health to be just as vital to overall health as diet and exercise."

Carroll urged new mothers take advantage of opportunities to get a little extra sleep, like taking naps during the day when their baby is asleep, accepting offers of assistance from family and friends, and, when possible, asking their partner to help with the baby during the night or early morning. "Taking care of your sleep needs will help you and your baby in the long run," she said.

Co-author Christine Dunkel Schetter, a distinguished professor of psychology and psychiatry at UCLA, said the study results "and other findings on maternal postpartum mental health provide impetus for better supporting mothers of young infants so that they can get sufficient sleep -- possibly through parental leave so that both parents can bear some of the burden of care, and through programs for families and fathers."

Dunkel Schetter added that while accelerated biological aging linked to sleep loss may increase women's health risks, it doesn't automatically cause harm to their bodies. "We don't want the message to be that mothers are permanently damaged by infant care and loss of sleep," she emphasized. "We don't know if these effects are long lasting."

'This aisle is closed': Using epigenetics to determine biological age

The study used the latest scientific methods of analyzing changes in DNA to assess biological aging -- also known as epigenetic aging, Dunkel Schetter said. DNA provides the code for making proteins, which carry out many functions in the cells of our body, and epigenetics focuses on whether regions of this code are "open" or "closed."

"You can think of DNA as a grocery store," Carroll said, "with lots of basic ingredients to build a meal. If there is a spill in one aisle, it may be closed, and you can't get an item from that aisle, which might prevent you from making a recipe. When access to DNA code is 'closed,' then those genes that code for specific proteins cannot be expressed and are therefore turned off."

Because specific sites within DNA are turned on or off with aging, the process acts as a sort of clock, Carroll said, allowing scientists to estimate individuals' biological age. The greater an individual's biological, or epigenetic, age, the greater their risk of disease and earlier death.

The study's cohort -- which included women who ranged in age from 23 to 45 six months after giving birth -- is not a large representative sample of women, the authors said, and more studies are needed to better understand the long-term impact of sleep loss on new mothers, what other factors might contribute to sleep loss and whether the biological aging effects are permanent or reversible.

Carroll and Dunkel Schetter reported last year that a mother's stress prior to giving birth may accelerate her child's biological aging, which is a form of "intergenerational transfer of health risk," Dunkel Schetter said.

Read more at Science Daily