Lethal effect of smoking on oocytes clarified
WESTPORT, CT (Reuters Health) - The polycyclic aromatic hydrocarbons (PAHs) found in tobacco smoke and elsewhere induce oocyte death by activating a preexisting apoptotic pathway rather than through some nonspecific toxic effect, according to a report pub
Cigarette smoking has been linked to early menopause, and animal studies have shown that PAHs induce oocyte death, but until now, the mechanisms involved were unclear, the authors state.
Dr. Jonathan Tilly, from Massachusetts General Hospital in Boston, and colleagues found that treating female mice with PAH compounds led to oocyte expression of Bax, a gene previously shown to initiate apoptosis. Further analysis revealed that the PAHs bind to an oocyte surface receptor known as the aromatic hydrocarbon receptor (Ahr), which then enters the nucleus to stimulate Bax expression.
Mice that were engineered to lack the Bax gene or the Ahr gene did not show oocyte death when exposed to PAHs, the researchers note.
To gauge the importance of the findings for humans, the researchers grafted human ovarian tissue under the skin of mice. Once again, a striking Bax-driven increase in degenerating oocytes was noted after treatment with the PAH compounds.
"We have been very interested for many years in the things that drive menopause," Dr. Tilly told Reuters Health. "With the link that has been established between smoking and early menopause, it raised some questions that the chemicals present in cigarette smoke may influence some apoptotic pathway."
"The Ahr evolved about 450 million years ago, but its natural ligand has remained elusive," Dr. Tilly pointed out. "No one knows what naturally stimulates this receptor, but the PAHs can subserve this role and pharmacologically turn the receptor on," he said.
"We have studied Bax-dependent apoptosis for several years and we've developed strategies for protecting the oocyte from this type of insult," Dr. Tilly noted. "Now that we know PAH binding of Ahr is tied to Bax-driven apoptosis, we can apply many of the protective strategies that we've already developed."