Healthy sperm, healthy children

There is growing evidence that epigenetic damage to sperm can result in negative health effects for generations of children.

August 21, 2015

Up to 3% of children are born with birth defects. Yet in two-thirds of these cases, the cause is unknown. There's increasing evidence that the father's health may play a greater role than previously thought in explaining birth defects and some adult-onset diseases, such as cancer.

"Numerous animal and human studies now indicate that exposure of the father to drugs and chemicals can result in infertility, embryo death, birth defects and cancer in children, and there's building evidence that a key underlying mechanism is epigenetic alterations to sperm," explains Dr. Jacquetta Trasler, professor in the Departments of Pediatrics, Human Genetics, and Pharmacology and Therapeutics at McGill University, and Director of the Developmental Genetics Laboratory at the Montreal Children's Hospital Research Institute.

Dr. Trasler's pioneer work has shown how exposure to environmental factors, such as chemotherapy or toxins, can damage sperm and cause health effects, including birth defects, in subsequent generations.

Her research has begun to document the precise ways in which men's sperm can suffer epigenetic damage. Her lab group discovered that the key epigenetic programming of future sperm cells occurs before birth, while female eggs are epigenetically "set" after birth. Her research has also revealed that the most common chemotherapy drugs used to treat testicular cancer causes distinct epigenetic changes in sperm – ones that can be passed on to children.

 "What our research is showing is that it's just as important for potential fathers as potential mothers to think about their behaviours, whether smoking or alcohol or exercise or stress-levels, before they decide to conceive," says Dr. Trasler.

In two major studies supported by the Canadian Institutes of Health Research (CIHR), Dr. Trasler is exploring the complex links between folate (or folic acid) intake, exposure to organochlorines (such as PCBs and DDT), sperm epigenetics and birth defects. Folate plays a key role in epigenetic modification. It is also well established that folate deficiencies in pregnant women can cause neural tube birth defects, such as spina bifida, and that the incidence of these defects can be reduced by adding folate to foods. But there may be more to the story.

"We have preliminary data from animal experiments that too much folate can also cause birth defects," says Dr. Trasler, noting that some infertile men are given high-dose folic acid therapy. In a study led by Laval University's Dr. Janice Bailey, Dr. Trasler will also help examine whether folate can prevent epigenetic changes in sperm in men exposed to high levels of organochlorine pollutants.

Epigenetics, environment and health

In the past five years, due to technological advances, epigenetics has emerged as a major area of health research and promise. While our DNA sequence is fixed, epigenetic characteristics are changeable. Epigenetics involves molecules, or marks, that regulate how the DNA is organized, and which genes are turned "on". Thus, epigenetic research could lead to new therapies, and successful epigenetic drugs are already used in cancer treatments.

CIHR is building epigenetics research capacity through STAGE, Canada's only formal training program in genetic and epigenetic epidemiology, and the Canadian Epigenetics, Environment and Health Research Consortium, which supports leading edge research on the role of epigenetic and environmental interactions in human health and disease.

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