Smoking can lead to premature ovarian failure, or early menopause, and scientists at Massachusetts General Hospital (MGH) have discovered how. The work published in the August issue of Nature Genetics and available online on July 16th could eventually have implications for fertility, menopause and overall womens health.
Weve uncovered a mechanism to explain why premature ovarian failure occurs following exposure to toxic chemicals in the environment., says principal investigator Jonathan Tilly, PhD, of the MGH Vincent Center for Reproductive Biology. Women who smoke undergo menopause earlier, and we've correlated this with exposure to a class of chemicals in tobacco smoke that accelerate the death of egg cells in the ovaries.
Tilly and his group found that cigarette smoke-derived chemicals called polycyclic aromatic hydrocarbons (PAHs) bind to a receptor called the AHR inside egg cells of the ovaries. This binding triggers the expression of a gene called Bax within an eggs nucleus. The elevated level of Bax then initiates a suicide command and the egg undergoes programmed cell death. Using mouse models, Tillys team also found that eggs with inactivated Ahr or Bax genes were resistant to PAH-induced death, indicating the functional importance of these two players in premature ovarian failure resulting from exposure to these toxic chemicals.
To demonstrate the relevance of their findings to humans, Tilly and his colleagues grafted human ovarian tissue under the skin of mice. After treating the mice with PAHs, they showed that Bax expression and programmed cell death indeed occurred in the human eggs within the grafts in a manner identical that that observed in mouse ovaries.
Because of the prevalence of PAHs in tobacco smoke, the current data strongly support the hypothesis that the early onset of menopause in women smokers is at least partly due to PAH-induced egg cell death, according to Tilly. His groups work has defined the act
Contact: Georgia W. Peirce
Massachusetts General Hospital