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Smoking in pregnancy 'could make unborn sons infertile'
Mothers who smoke early in pregnancy may sow the seeds of infertility in their unborn sons by arresting the development of sperm cells, new research suggests.
Scientists found numbers of immature reproductive cells were dramatically reduced in male embryos exposed to the effects of tobacco.
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The findings echo those of previous research showing a similar effect on female embryos.
They were published alongside the results of a second study explaining why men who smoke may be putting their fertility at risk.
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The new work sheds further light on the links between smoking and infertility, and reinforces public health advice urging couples to quit the habit before attempting to conceive.
The first team led by Professor Claus Andersen, from the University Hospital of Copenhagen in Denmark looked at 24 embryonic testes obtained from legally terminated pregnancies.
Each of the aborted male embryos was between 37 and 68 days old.
The scientists compared the number of germ cells - immature cells that become sperm in males and eggs in females - in the testes of embryos from smoking and non-smoking women.
Those from smokers contained less than half as many germ cells as those from non-smokers. The number of non-reproductive somatic cells was also reduced by more than a third in the testes of embryos from smoking mothers.
The effect was dose dependent, so that the more a woman smoked the more impact it had on the embryo.
Previous research looking at the effect of smoking on female embryos found a similar pattern, said the researchers writing in the journal Human Reproduction.
Overall, the number of germ cells in male and female embryos exposed to tobacco smoke were reduced by 41%.
Professor Andersen said: "As the germ cells in embryos eventually develop to form sperm in males and eggs in females, it is possible that the negative effect on the numbers of germ cells caused by maternal smoking during pregnancy may influence the future fertility of
offspring.
"In addition, the reduction in the number of somatic cells also has the potential to affect future fertility, as somatic cells in the testes support the development of germ cells to form functional sperm. If the somatic cell number is reduced, fewer functional sperm will be produced."
The findings may help to explain the trend towards reduced fertility seen in recent years, said Prof Andersen.
He added: "Although the prevalence of smoking during pregnancy has declined in the last decade in developed countries, one in eight mothers continue to smoke throughout their pregnancy, and in Denmark the prevalence of smoking actually increased to 43% in 2005 among women younger than 20 at the time of delivery.
"This tendency is alarming, and when you take the results from this study in combination with the other known negative effects of cigarette smoke during pregnancy, it further emphasises that pregnant mothers should refrain from smoking."
Prof Andersen stressed that the first three months of pregnancy was a crucial time when the developing embryo's sexual organs are differentiating to form either male testes or female ovaries.
"This process is very delicately regulated, with a number of hormones fluctuating," he said. "If something goes wrong at this point, just six to eight weeks after conception, it may have an impact on the function of the gonads later in life.
"Our results show that the gonads are susceptible to factors, such as cigarette smoke, just at this critical time when they start to differentiate."
The scientists still do not know whether the reduction in embryonic cell numbers associated with smoking is permanent, or reflects a growth delay that is compensated for later on.
"We would expect adverse effects to be more pronounced if the mother continues smoking throughout pregnancy, but we have only studied gonads from the first trimester and can only guess whether this effect actually will occur," said Prof Andersen. "So the effect on future fertility is still unknown. However, this study does indicate that smoking during pregnancy may have an adverse effect on the future reproductive ability of offspring, since both the number of germ cells and somatic cells are dramatically reduced and these are the foundations of future fertility."
The second study, also published in Human Reproduction, focused on levels of proteins called protamines that play an important role in the development of sperm.
A team led by Professor Mohamed Hammadeh, from the University of Saarland in Homburg Saar, Germany, looked at the levels of two protamines - P1 and P2 - in the sperm of 53 heavy smokers and 63 non-smokers.
The proteins help to "package" DNA into chromosomes that can fit inside cells. If something goes wrong with this process it can lead to fertility problems in men and a higher rate of miscarriages.
The scientists found that, compared with non-smokers, P2 concentrations were 14% lower in the sperm of men smoking more than 20 cigarettes a day.
In addition the relative levels of P1 and P2 were altered in smokers.
Prof Hammadeh said: "In normal fertile men, the ratio of P1 to P2 is almost equal at 1:1. Any increase or decrease in this ratio represents some kind of infertility.
"In this study the ratio was significantly higher in smokers than in non-smokers, with higher levels of P1 than of P2."
He added: "Given the potential adverse effects of smoking on fertility, cancer and so on, physicians should advise infertile patients who smoke cigarettes to quit smoking."
Fertility expert Dr Allan Pacey, senior lecturer in andrology at the University of Sheffield, said: "These two studies provide further proof that the smoking of cigarettes is bad for the reproductive system of men and women.
"Clearly couples trying to conceive should not smoke and should avoid exposure to cigarette smoke. To make sure sperm are healthy, this needs to be sustained as it takes about three months to produce a cohort of sperm: stopping smoking on Friday does not mean healthy sperm by Monday.
"Furthermore, once a woman is pregnant, it is vitally important that she does not smoke and that the baby is not exposed to the harmful chemicals contained in cigarette smoke whilst it is developing.
"It breaks my heart to see pregnant women having a crafty cigarette outside the maternity hospital in Sheffield where I work.
"That is not the best start in life for any baby. But equally we need to recognise that, for some people, stopping smoking is hard and we need to support them to give up."
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Friday 25 May 2012
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