Saturday, December 29, 2007

Smoking Before, After Pregnancy Harms Daughters' Fertility

Smoking Before, After Pregnancy Harms Daughters' Fertility
WEDNESDAY, Nov. 21 (HealthDay News) -- Researchers haveidentified the chemical pathway by which a mother's smoking before andafter pregnancy might reduce her daughter's fertility by as much astwo-thirds.
Cigarette smoking during pregnancy has been shown in retrospectivestudies to affect the fertility of a woman's offspring, but this is thefirst study to offer an explanation of the biology behind the effect, theCanadian scientists claim.
A team at the Samuel Lunenfeld Research Institute at Mount SinaiHospital in Toronto investigated the impact of polycyclic aromatichydrocarbons (PAH), a byproduct of smoking, on mouse fertility.
Researchers injected three groups of female mice with a low-dosemixture of PAH: One group received PAH before conception and again whenthey were providing milk for their pups; one group received PAH onlybefore conception; and the third group received PAH only during lactation.A fourth control group did not receive PAH but were mated at the same timeas the others. The total amount of PAH given to each mouse over thethree-week injection cycle was equivalent to 25 packs of cigarettes,according to the researchers. The exposed mice did not have fewer pups intheir own litters, but when researchers investigated the number of eggs intheir female offspring, they found about 70 percent fewer folliclesavailable to produce eggs.
"Mothers, mice in this case, exposed to PAHs -- environmentalpollutants found in cigarette smoke, car exhaust, smoke produced by fossilfuel combustion, as well as in smoked food --before pregnancy and/orduring breast-feeding, but not during pregnancy, can cause a reduction inthe number of eggs in the ovaries of their female offspring by two-thirds.This limits the window in which the daughter will be able to reproduce,"explained lead researcher Dr. Andrea Jurisicova.
Further analysis indicated that the effects of PAHs on the number offollicles in female offspring were mediated through a receptor thataffects the expression of a gene that makes a protein that causes cells todie. The researchers then demonstrated similar effects in human ovariantissue transplanted into immunocompromised mice.
Jurisicova described the process: "Toxic compounds were injected underthe skin of mice and were picked up by the bloodstream and carriedthroughout the body until they reached the ovaries. Once at the ovaries,they passed through the cell membrane and bound to the receptor. When thishappens, it activates the receptor, which then enters the cell nucleus.The receptor then finds a specific DNA sequence that turns on the gene,which accumulates and eventually kills the eggs."
"This study now is providing a chemical pathway, which is very nice,"said Dr. Norman Edelman, consultant for scientific affairs with theAmerican Lung Association. The new data provides biological support forepidemiological results, such as the previously observed reduction infertility among daughters of smoking women, he added.
Whether the news will have an impact on a woman's decision to smoke isanother question, said Edelman.
"If we do our job right and these results get good press, this datacould remind women of what they are doing to their unborn fetuses,"Edelman said.
Another expert noted this latest finding adds to a growing body ofevidence that shows a strong connection between smoking and fertility.
"I think it is an interesting study, but it doesn't add much new. Otherstudies have shown similar outcomes. The theory is that smoking couldaffect the follicles or the fallopian tubes," said Dr. Amos Grunebaum,director of obstetrics at New York Weill Cornell Medical Center, in NewYork City. "We have known for many years that smoking affects fertility onmany levels."
"The key is women should quit smoking before they are thinking ofgetting pregnant," Grunebaum said.
The Canadian researchers did offer some good news in their report,published in the Dec. 3 edition of the Journal of ClinicalInvestigation. Injecting resveratrol in the mice who were exposed toPAH prevented the reduction in egg follicles in their offspring.Resveratrol is a naturally occurring antioxidant found in wine and grapeskins. However, that reversal of damage does not mean that women who smokecan counter the effects with a nutritional supplement or a glass of redwine, the researchers stressed.
"We have found that oral consumption of resveratrol as a foodsupplement, at least in mice, is not effective, as levels of resveratroldo not reach sufficient amount in the bloodstream to provide protection,"Jurisicova said.
Although the findings do not define the length of time between quittingsmoking and healthier fertility in offspring, Jurisicova noted thatprevious studies have shown that women who smoke have better results within vitro fertilization one year after they quit smoking. The micein the current study conceived up to two weeks after their final PAHinjection, which is approximately equivalent to three menstrual cycles inwomen.
The effect of a mother's cigarette smoking is not limited to her femalechildren. A study published in the Jan. 1 issue of the American Journalof Epidemiology suggested that the male offspring of mothers who smokehave lower sperm counts.
There is still more research to be done, Jurisicova noted.
"We hope to continue studying the female offspring to see if they enterthe mouse version of menopause earlier than mice whose mothers were notexposed to PAHs," Jurisicova said. "We also hope to study if their reducedfertility passes on to subsequent generations, and if the granddaughtersare predisposed to similar problems."
More information
Need to quit smoking? Visit the U.S. SurgeonGeneral or the National Institutes of Health.

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