There's more and more evidence that men's lifestyle and environment long
before they have kids can affect their future children's health. Now, a
Canadian-led study has shed some light on how and why that effect occurs.
When the researchers changed signals on proteins called histones in the sperm
of male mice, their offspring and even their grandchildren had increased birth
defects, mortality and stunted growth, they reported in the journal Science. The signals that were
changed are the type of signals that are affected by environmental factors such
as food, drugs and stress in both mice and humans.
"We didn't expect these lasting effects across generations from changing a
protein in one generation," said Sarah Kimmins, an associate professor of
reproductive biology at Montreal's McGill University, the senior author of the
"It's a completely non-DNA based transmission of this abnormal development."
their health before conception and during pregnancy, Kimmins says the
new discovery emphasizes that what's transmitted in the father's sperm is
also essential to the health and development of the offspring.
"It's another critical piece of information that says we really need to start
looking at fathers' pre-conception health," she said. "And that's a message
that's really missed in society."
Kimmins said there are two main kinds of evidence that have shown that men's
(and other male mammals') environment before conception affects their
- Epidemiological studies that link things such as a father's smoking and diet
with their children's and grandchildren's health, growth and risk of health
problems such as cardiovascular disease.
- Lab studies in animals making a direct link between a father's diet, stress
and exposure to drugs or toxic substances with their offsprings' health.
father across generations," Kimmins added.
It's well-known that fathers pass on DNA and genes to their offspring, but
those genes and DNA don't change much except for rare mutations.
More recently, scientists have started looking at signals called methylation
that attach to the DNA to turn genes up or down. Those signals are part of the
"epigenome" – a system that affects the way genes are expressed.
Kimmins and her team decided to look at histones because they're also part of
the epigenome and they're found in sperm in tiny amounts. They act like spools
that DNA wraps around, and they organize the DNA, opening it up to make genes
available to make proteins, or closing the DNA to stop genes from working. They
also help direct other proteins involved in gene regulation.
Most interestingly, new research had shown that histones are associated with
DNA involved in development of both mice and humans during pregnancy.
Kimmins and her team created transgenic mice with a faulty gene that caused
unusual methylation in the histone proteins in their sperm.
Kimmins and her team created transgenic mice with a
faulty gene that caused unusual methylation in the histone proteins in their
They found that the offspring of those mice were far more likely to die
shortly after birth or have birth defects such as limb, skeletal and facial
deformities. Many others also had skin problems or stunted growth.
The problems even extended to the grandchildren of the transgenic mice, even
if they and their parents didn't inherit the faulty gene, showing this wasn't a
genetic effect involving DNA, but could still be passed down through
While a gene was originally responsible for changes to the epigenome in this
case, the same kinds of changes are known to be caused by environmental factors
such as stress and diet.
Kimmins is confident the same effects would be seen in humans as mice because
humans have very similar histone proteins in their sperm that interact with the
same genes in the same places.
Kimmins and her colleagues are now trying to determine whether they can
observe epigenetic changes in the sperm of humans – a group of men in Toronto
and a group of men in Africa – linked with their diet and their exposure to
substances such as alcohol.