MONDAY, July 16, 2001 (HealthDayNews) -- Women considering motherhood have a new reason to avoid tobacco smoke.
A class of chemicals released by burning cigarettes triggers a process leading to the death of immature egg cells in mice, American, Canadian and Japanese scientists report.
And the researchers speculate that chemicals in tobacco smoke could kill up to half the eggs in the ovaries of women who smoke.
Researchers say compounds, called polycyclic aromatic hydrocarbons (PAHs), lock on to a receptor on immature egg cells, also known as primordial oocytes. That triggers a gene, called Bax, that kickstarts a process of cell death called apoptosis. The process is described in today's issue of Nature Genetics.
Senior study author Jonathan Tilly, director of Massachusetts General Hospital's Vincent Center for Reproductive Biology in Boston, says scientists have thought for years that smoking can lead to premature menopause in women. While the average age of menopause in the United States is 50 or 51, studies suggest that women who smoke start menopause two to three years earlier.
Tilly says premature menopause primarily is due to the accelerated loss of eggs, but until now, no one knew how cigarette smoke might cause that effect.
The researchers tested the effect of PAHs on immature eggs in the ovaries of both normal mice and mice with grafted human ovaries containing primordial oocytes. "These chemicals, for whatever reason, target the primordial population of eggs," those that haven't started the maturation process kickstarted by puberty, says Tilly.
Tilly found that the PAH binds to an aromatic hydrocarbon receptor (Ahr) on egg cells, inducing the action of the Bax gene. "This gene includes a protein that impacts negatively on the function of an organelle with the cell called mitochondria, the energy powerhouses of cells," says Tilly. "They make all the energy that a cell uses to survive." Once the mitochondria stops working, the egg cell, starved of energy, dies.
Tilly says previous studies found that young women who had one ovary removed, leaving them with half their egg supply, went into menopause two to three years earlier. "By assumption, we can almost extrapolate that women who smoke are probably killing up to half of their egg population," he says.
Because the effect is cumulative, Tilly says a woman who starts smoking just before menopause might not do much damage, but, "If a teenager starts smoking and continues to smoke throughout her 20s and into her 30s, you really have to raise the flag that she's probably doing some fairly substantial damage to her ovaries."
Tilly also says healthy women begin to notice a substantial decline in fertility in their late 30s or early 40s. If that happens two to three years earlier because a woman smokes, Tilly says the window to have children shrinks further, especially for women whose careers have forced them to postpone childbearing.
While it might seem bizarre that receptors on human egg cells would bind to pollutants, Tilly says the Ah receptor evolved roughly 450 million years ago and is found in many different animals. The fact that it still exists suggests that it's a binding site for something else, but scientists don't yet know what that is.
However, cigarette smoke is not the only source of PAHs, Tilly says. Aluminum or coal processing plants, municipal incinerators and road or roof tarring operations also produce PAHs. The U.S. Environmental Protection Agency's Integrated Risk Information System says seven types of PAHs are probable human carcinogens.
Tilly says the study raises hope that the process could be interrupted to prevent premature egg cell death.
Jerrold Heindel, a biological chemist and a scientific program administrator at the National Institute of Environmental Health Sciences in Research Triangle Park, N.C., says the key is this new knowledge of the molecular mechanism of PAH's role in egg cell death.
"Once we know what the mechanism is, there may be ways to be able to block it," says Heindel.
"If PAH binds to the Ah receptor and then stimulates this pathway, we can do one of two things. [We can] put a more vigorous campaign to reduce the PAHs so they don't get to the high concentrations to cause that effect. Or, if that's not possible, we may be able to find agents that are antagonistic that can be taken that would block the effect of PAH on that pathway," Heindel says.
The study, which was funded by the National Institute of Environmental Health Sciences, is part of a program of research into the role of environmental chemicals in male and female reproduction and development.
What To Do
Heindel says many chemicals in cigarette smoke are toxic to the ovaries. Smoking also is a leading risk factor for lung cancer and coronary heart disease. If you smoke and are pregnant or considering having children, talk to your doctor about a smoking cessation program.
The Agency for Toxic Substances and Disease Registry provides information on PAHs, or check this online book from National Academy Press.
The American Society for Reproductive Medicine publishes this booklet called Age and Fertility. (You will need to download Adobe Acrobat Reader to read it.)
