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Prenatal effects on sperm production in adult males

10 May 2010
By Professor Allan Pacey
Senior Lecturer in Andrology at the University of Sheffield
Appeared in BioNews 557
Nearly 10 years ago, Professor Niels Skakkebæk from the Copenhagen University Hospital, published details of a new syndrome to account for the apparent increase in problems related to the male reproductive system that had been documented in many countries (1). These problems included increasing incidence of testicular cancer and undescended testicles, and apparently lower sperm counts in some young men in comparison to their fathers' generation.

The syndrome, termed 'Testicular Dysgenesis Syndrome', had at its core the notion that the testicle might be sensitive to chemicals in the environment and diet which led to increased risk of cancer or poor fertility in some men. No surprise there, you may say. But importantly, the theory proposed that is was not exposure in adult life that was important, rather exposure of the testicle in pre-natal life that might be more critical in determining the risk of cancer or infertility in adult life.

The idea of something happening before an individual is born that could affect their health in adult life was new. A few years before, Professor David Barker, working at the University of Southampton, had published data (2) suggesting that an individual's risk of heart disease in adult life might be related to their birth-weight and therefore, by inference, the quality of the pregnancy they enjoyed in fetal-life.

To study such trans-generational effects is clearly very difficult, particularly in human populations where the generation time is so long. There are obvious ethical and technical limitations of performing any kind of interventional experiment to prove these theories one way or the other. Yet, when data sets emerge which allow us to test them, they invariably fit to a lesser or greater extent.

Take, for example, the data on smoking cigarettes. The studies that have examined the effect on sperm counts of men smoking cigarettes show that there is only a small influence at best: the sperm counts of men who smoke cigarettes are largely similar to those of men who do not (3). But when data sets compare the sperm counts of men whose mothers smoked during pregnancy a much larger effect is seen: sperm counts of men born to women who smoked are significantly lower than those of men whose mothers didn't smoke (4).

This is just one example, and it is important to note that this is not an endorsement to would-be fathers to continue (or start) smoking when they are trying to achieve a pregnancy: smoking is known to damage sperm DNA (5), which probably contributes to infertility. But the data do illustrate the point that the number of sperm that men are able to produce may not necessarily be attributable to his lifestyle and exposures as an individual. Rather, it may have already been established before he was born.

At a conceptual level, it is very difficult for individuals to attribute their own life events with something that their mothers may have done or been exposed to before they were born. As such, the theories of Barker or Skakkebæk are still not as widely recognised as they should be. Therefore, when journalists write articles about what may affect male fertility they invariably jump straight to the obvious and concern themselves only with what men should or shouldn't do with their lives to retain whatever sperm production capacity they have. Sadly, they tend to ignore the rather interesting biological processes that occur many years earlier and which are probably more important.

It was with some pleasure and surprise, therefore, to see some better reporting in the Daily Telegraph (6) and Daily Mail (7) newspapers concerning the very comprehensive review of the topic by Professor Richard Sharpe at the University of Edinburgh, Scotland (8). Perhaps, finally, we are getting the message across that sperm counts are about more than just the man and his lifestyle.
1) Skakkebaek N. E., Rajpert-De Meyts E., Main K. M., (2001) Testicular dysgenesis syndrome: an increasingly common developmental disorder with environmental aspects
Human Reproduction 16: 972-978 |  23 October 2021
2) Barker D. J., (1995) Fetal origins of coronary heart disease
British Medical Journal 311: 171-174 |  23 October 2021
3) Vine M. F., Margolin B. H., Morrison H. I., Hulka B. S., (1994) Cigarette smoking and sperm density: a meta-analysis
Fertility and Sterility 61: 35-43 |  23 October 2021
4) Ramlau-Hansen C. H., Thulstrup A. M., Storgaard L., Toft G., Olsen J., Bonde J. P., (2007) Is prenatal exposure to tobacco smoking a cause of poor semen quality? A follow-up study
American Journal of Epidemiology 165: 1372-1379 |  23 October 2021
5) Sepaniak S., Forges T., Gerard H., Foliguet B., Bene M. C., Monnier-Barbarino P., (2006) The influence of cigarette smoking on human sperm quality and DNA fragmentation
Toxicology. 223: 54-60 |  23 October 2021
6) Women who are obese or smoke during pregnancy 'can low sperm count in sons'
The Daily Telegraph |  19 April 2010
7) Mothers-to-be who smoke 'can harm son's fertility' say scientists
The Daily Mail |  19 April 2010
8) Sharpe R. M., (2010) Environmental/lifestyle effects on spermatogenesis
Philosophical transactions of the Royal Society of London, Series B, Biological sciences 365: 1697-1712 |  23 October 2021
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