Biohazard: smoking before or after pregnancy may harm daughters' fertility.

Exposing female mice to chemicals found in cigarette smoke before pregnancy or during the period in which they nurse their young impairs the reproductive capacity of their female offspring, a new study finds.

Many women stop smoking when they discover they are pregnant, aware that this habit endangers the baby. The new data suggest that may not be enough to protect their daughters' long-term reproductive health.

In mammals, females develop their lifetime supply of eggs--housed in the ovaries--while still in the womb or shortly thereafter. At menarche, women gradually begin to lose this dowry through monthly ovulation until their eggs run out at menopause.

However, data had suggested other factors, including cigarettes, can cut into egg reserves. For instance, women who smoke tend to reach menopause sooner than nonsmokers.

To test whether this risk is passed along to offspring, scientists injected female mice with two chemicals found in cigarette smoke, benzo(a)pyrene and 7,12-dimethyl-benz(a)anthracene. Mice got one injection weekly for 3 weeks in doses that mimicked amounts ingested by a woman who smoked at least a pack of cigarettes a day. The scientists accounted for weight differences.

Shortly afterward, the mice became pregnant and delivered normal-size pups. Ovaries in the female pups were not normal, however. Examined shortly before the pups reached puberty, these ovaries had one-third fewer eggs than pups born to unexposed mothers, the researchers report in the December Journal of Clinical Investigation.

Another group of female adult mice exposed to the cigarette-smoke chemicals only after pregnancy, while suckling newborn pups, had female young with a similar dearth of eggs. Finally, female pups whose mothers were exposed to the chemicals before pregnancy and during lactation were missing two-thirds of the normal egg supply, notes study coauthor Andrea Jurisicova, a molecular biologist at the University of Toronto.

The most obvious explanation for the losses, Jurisicova says, "is that the [smoke] compounds are hanging around in the mom" and getting released during pregnancy or lactation. The chemicals may accumulate in fat, and then leach out slowly. "It's very likely that the compounds affect the primordial germ cell population being formed," she hypothesizes.

Smoking before pregnancy or during lactation poses a biohazard to the offspring's health, Jurisicova and her colleagues conclude.

Further experiments showed that resveratrol, a chemical derived from the skin of grapes, prevents egg loss. Female mice born to mothers given resveratrol had normal egg reserves, even when their mothers had also been exposed to the smoke chemicals. Research has suggested resveratrol offers a host of health benefits (SN: 11/4/06, p. 293). These now might include the ability to rescue germ cells from chemicals that would switch on a self-destruct mechanism, Jurisicova says.

"This is very interesting work indicating that maternal cigarette smoking may have transgenerational effects" says Jodi A. Flaws, an epidemiologist at the University of Illinois at Urbana-Champaign. "Future studies should examine whether there are similar effects ... in humans."