Although you don't read about it in the Surgeon General's warning on cigarette packs, smoking decreases a woman's fertility and leads to early menopause. Now researchers report how a chemical in cigarette smoke destroys egg cells. Understanding this pathway may suggest ways to head off some of the toxic effects of this family of chemicals, which are produced not just by cigarettes but by almost anything that burns.
Female smokers go through menopause several years earlier than nonsmokers, on average, and a few years ago a team of molecular biologists led by Jonathan Tilly of the Massachusetts General Hospital in Boston reported that egg cell death was responsible. When the eggs-in-waiting that support a female's fertility are killed, their enveloping follicles, which release reproductive hormones such as estrogen, also die. Earlier work had shown that chemicals called polycyclic aromatic hydrocarbons (PAH), which are found in cigarette smoke, can kill mouse eggs, so the team set out to find out how PAHs do their damage.
The researchers suspected that PAHs triggered apoptosis, or programmed cell death, in eggs. Sure enough, they found two regions of DNA that recognize PAHs and then start a chain reaction of gene expression that ends in apoptosis. Although all cells have this DNA, eggs seem uniquely susceptible. Mice engineered to lack either a PAH receptor or the gene that causes apoptosis weren't harmed by injections of PAH, but normal mice lost most of their egg cells. Human egg cells behaved the same way; when human ovary tissue was grafted into mice injected with PAH, the eggs died, the team reports in Nature Genetics online this month.
Tilly's team demonstrated a remarkably tight and specific chain of events leading to egg cell death, says Jerrold Heindel, a toxicologist at the National Institute of Environmental Health Sciences in Research Triangle Park, North Carolina. "This is the first time we've got a direct molecular mechanism relating this particular receptor to apoptosis."