EPIGENETICS: CAN YOUR ACTIONS TODAY AFFECT YOUR
GRANDCHILDREN'S GENES AND BEHAVIOR?

Drugs given to pregnant animals can affect the brains and behavior of at least two generations of offspring, Toronto researchers say. The finding adds to evidence that dietary intake, drug use, toxic exposure, and other environmental factors can cause "epigenetic" effects-that is, changes in gene function that occur in the absence of changes in DNA sequencing and that can be inherited by future generations.

Stephen Matthews and colleagues studied the effects of betamethasone, a synthetic glucocorticoid drug, on the offspring of guinea pigs. Doctors frequently give beta- methasone to pregnant women at risk of delivering very prematurely, because a single dose can markedly reduce the death rate of their babies. However, babies who do not arrive as prematurely as expected can be exposed to many courses of the drug.

The researchers used guinea pigs because the animals' placentas are similar to humans' and they give birth to similarly mature offspring. The animals were divided into three groups, with one group receiving three injections of betamethasone, a second group receiving three injections of saline, and the third group receiving no injections at all.

As expected, offspring of the drug-exposed guinea pigs were hyperactive-an effect also documented in human infants of women given multiple doses of betamethasone. However, the researchers discovered that when affected female offspring mated with normal male guinea pigs, their offspring-the grandchildren of the original drug-exposed animals-also exhibited behavioral abnormalities. Males showed little interest in exploring new surroundings, while females were hyperactive and made odd vocalizations.

The study's results are consistent with other research showing that dietary changes or exposure to toxins can cause epigenetic changes affecting future generations. One study, for instance, found that when pregnant rats were exposed to a high dose of a particular pesticide, 90% of male offspring in the next four generations exhibited reproductive problems.

"Pregnancy drugs can affect grandkids too," New Scientist, December 3, 2005, www.newscientist.com. Address: Stephen Matthews, Dept. of Physiology, Medical Sciences Bldg. Room 3240B, 1 King's College Circle, University of Toronto, Toronto, Ontario, Canada M5S 1A8, stephen.matthews@utoronto.ca.