Paternal smoking associated with lower total sperm counts

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The adverse effect of maternal smoking during pregnancy is well established and associated with several negative neonatal outcomes (such as low birth weight and preterm birth). It is also evident in some studies that the semen quality of men exposed to prenatal maternal smoking is generally more impaired than that of unexposed men.(1) However, there is little known about the effect of paternal smoking in the time leading up to and during pregnancy.

Now, preliminary results from a large population study based on the Danish National Birth Cohort has found that paternal smoking is associated with lower total sperm counts and sperm concentrations independent of maternal smoking and other confounding factors (such as age, alcohol consumption or BMI).

‘There have been previous studies investigating the association of paternal smoking with semen quality but these were small studies without information on key confounders,’ said investigator Dr Sandra Søgaard Tøttenborg from Bispebjerg Frederiksberg Hospital, in Copenhagen, Denmark. ‘Our larger study does support these previous findings that paternal smoking is associated with sperm concentrations in male offspring independently of maternal smoking. We also found the association was independent of other preconceptional and prenatal risk factors for adult semen quality – including parental age, alcohol and caffeine consumption, pre-pregnancy BMI, and household occupational status.’ The results were presented by Tøttenborg at the 35th Annual Meeting of ESHRE in Vienna.

The study was a follow-up analysis of 778 19-year-old young men born to mothers registered in the Danish National Birth Cohort between 1996 and 2002. Smoking information (including that on the father) was based on a maternal report around gestational week 16. Semen quality in the young men was analysed according to WHO criteria to include sperm concentration, total sperm count, morphology and sperm motility.(2)

Results showed that in the adjusted analyses the sons of fathers who smoked daily (and where the mothers did not smoke) had a 8% lower sperm concentration and 9% lower total sperm count than the sons of paternal non-smokers.(3)

‘Our results did show an association with paternal smoking,’ said Tøttenborg, ‘but the effect of maternal smoking is much larger. If the mother but not the father smoked, the reduction was 26% for sperm concentration and 46% for sperm count. It’s certainly worse for the boys if the mother smokes. Nevertheless, the circumstances in which the father smokes but the mother doesn’t is much more prevalent, so this is still very relevant for public health. A decline in sperm count of 8-9% can seriously affect the fertility of men with already sub-optimal sperm quality.’

Tøttenborg added that, while the association with sperm count and concentration observed in this study is not dramatic when compared to other known risk factors (such as exposure to certain pesticides and some urogenital disorders such as cryptorchidism), it still remains in the same range as that associated with smoking in the adult man.

The likely explanation for a pre-conceptional or prenatal effect of paternal smoking in the offspring is epigenetic, by which paternal smoking can induce alterations in the sperm genome which in turn may be transmitted to the cells of the offspring.

Abstract
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In his reaction to the research, Dr Rod Mitchell, consultant paediatric endocrinologist and group leader, MRC Centre for Reproductive Health, University of Edinburgh, said: “The association between ‘in-utero’ exposures and future reproductive health of the male offspring are well established in animal models, supported by association studies in humans.

“Ruling out alternative explanations (alcohol consumption or BMI) for associations (between smoking and sperm count in the adult sons) is a particular strength of the study design.

“The reported reduction in sperm count (46%) when the mother smokes would be expected to have a direct effect on fertility in some sons. However, the reported reduction in sperm count if the father smoked was much more modest and importantly was non-significant, meaning it could simply be due to chance alone.

“If such an association between paternal smoking and sperm count in sons were proven, this could represent direct effects of smoking on the father’s sperm, or alternatively it may be a result of in-utero effects of exposure to passive smoking on foetal testicular development. However, the study does not explore a mechanism for this reported association.

“Given that major health risks of smoking are well recognised, this study may indicate yet another reason to consider modification of this lifestyle factor. Importantly, whilst the study appears to have been conducted in a robust fashion, the study requires scientific peer-review and publication before definitive conclusions can be drawn.”

Professor Richard Sharpe, MRC Centre for Reproductive Health, University of Edinburgh, and member of the Society for Endocrinology said: “We have known for some time that smoking by mums in pregnancy is associated with up to a 40% decrease in sperm count in resulting sons when they become adults, based on 4 independent studies; and of course, maternal smoking is associated with numerous other long-term adverse health effects for the resulting babies. What the latest Danish study shows for the first time, apart from confirming these 4 previous studies with regard to maternal smoking ‘effects on sperm count’, is that smoking by the father during the pregnancy that gave rise to his son, is also associated with a non- significant but slightly adverse effect on his son’s sperm count, albeit of smaller magnitude than that found if the mother smoked.

“This may be yet another brick in the wall showing the harmful effects of passive smoking. The study appears sound and utilises the superb medical databases available in Denmark. Whilst this is an association study, and therefore does not prove that paternal and/or maternal smoking during pregnancy causes a decrease in sperm count in resulting sons, the consistency of the findings (for maternal smoking) in now 5 independent studies makes it more likely that this is cause and effect.

“Assuming this to be the case, we still do not know the mechanism, although top of the list would be that smoke chemical exposure reduces the rate at which the Sertoli cells in the foetal testes increase in number, as it is the final number of Sertoli cells that determines the ceiling of sperm production (and thus sperm count) in adulthood.”

Professor Allan Pacey, professor of andrology, University of Sheffield, said: “This is an interesting study which highlights a small but potential link between a man’s sperm quality and the lifestyle of his parents. We now know that many aspects of adult health, including fertility, are established very early in life before we are born. Therefore, to date, most investigations into this area have tended to focus on the health and lifestyle of the mother. For example, previous studies have shown that the sperm quality of men whose mothers smoked during pregnancy are significantly lower than those whose mothers didn’t. However, very little attention has been focussed on the lifestyle of the father (presumably because he isn’t the once carrying the pregnancy).

“In this study, a small but non-significant effect is seen on the sperm quality of son’s born to partnerships where the father smoked but the mother didn’t. The authors conclude that this could be because the fathers smoking causing genetic changes in his sperm that were then passed onto his son. This may be true. But I do wonder if it simply a case of ‘passive smoking’ by the mother as presumably the fathers and mothers of these males shared a common household?

“However, regardless of the precise biological effect, the data does serve to illustrate the need for both future fathers and mothers to be as healthy as possible, both before and during a pregnancy.”

ESHRE material
Science Media Centre material


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