The NIPH is collaborating with British researchers to study the effects of various environmental toxins on spermatozoa. The researchers looked at benzo[a]pyrene, a substance that is present in cigarette smoke but which is also present in other sources such as grilled food and diesel exhaust. We are exposed to this compound on a daily basis, mainly via ingestion. On top of this smokers have significantly higher levels of benzo[a]pyrene in the body than non-smokers.
Damage to the male germ cells in the testicle
Sperm develop from the male germ cells that divide several times before they undergo an extensive maturation process to become ready to fertilise an egg. The researchers examined sperm cells from mice in various stages of development and studied the effects of benzo[a]pyrene. The results show that the paternal genome in the mature sperm could be compromised irrespective of which stage the environmental impact occurred during spermatogenesis. However, the type of damage varied with spermatozoal development stage.
What do these results mean for fertilisation?
" If the sperm cell is damaged in the later stages of maturation, it can affect sperm quality. Sperm cells with DNA damage are less able to fertilise eggs and also to give rise to a full-term pregnancies. Fertilisation with spermatozoa with damaged DNA can cause early miscarriage because the development of the embryo in disturbed," said researcher Ann-Karin Olsen at the Division of Environmental Medicine, NIPH.
Increased likelihood of disease in offspring
Can damaged spermatozoa cause disease in the next generation?
“We believe that such damage may lead to increased risk of disease in the offspring, but there is a difference between the effects of the injuries to germ cells and the damage to "semi-mature" and almost mature spermatozoa. Damage to the stem cells in the testicle is serious because these are mutations which will also be found in all the cells in the offspring," said Olsen.
“When it comes to damage to the "semi-mature” and nearly mature cells, we know that such spermatozoa can fertilise an egg even with a lot of damage. However fertility is reduced and the embryonic development is disturbed. We know little about the subsequent effects of such damage on disease development in the offspring,” continued Olsen.
Not directly transferrable
Olsen adds that these research results cannot be applied directly to humans because experiments are conducted in mice using much higher levels of benzo[a]pyrene than humans are normally exposed to, although knowledge about the mechanisms is very important. However, the research results are consistent with other observations. It has already been established that for couples undergoing IVF treatment to have children, male smokers are less likely to become a father than non-smokers. Moreover, studies show a correlation between paternal smoking and the risk of certain cancers in children.
Do not wait too long
Do men who smoke damage their spermatozoa permanently?
“We must distinguish between injury to the stem cells for the sperm and damage to sperm during development. If the stem cells aquire DNA mutations, any spermatozoa that develop from these cells will carry these mutations. DNA damage inflicted during the final weeks before conception are not yet mutations, but have the potential to be transformed into mutations, and they will cause poor sperm quality and thereby reduce the likelihood of having children.”
Is it possible to avoid damage, besides being a non-smoker?
“I would recommend to be conscious of everyday choices with respect to exposure to harmful chemicals, they should be avoided as much as possible. It has been shown that other substances can damage spermatozoa in the same way as benzo[a]pyrene. It is wise for men to consider what they expose themselves to before planning to conceive. It takes about three months from when a stem cell begins to divide until mature sperm is generated. In addition, men should not wait too long to have children because the genetic changes accumulate with time," says Olsen.
Maternal smoking can also cause damage
Norwegian and Danish men have lower sperm quality than men from Finland, Sweden and the Baltic states. The researchers speculate that this is because women began smoking earlier in Norway and Denmark than in other countries. There is now evidence that women's smoking during pregnancy has a consequence for testes development in male foetuses and their future sperm quality.
The research project at the NIPH continues with several studies. The researchers will study what happens when low doses of benzo[a]pyrene are used over longer periods, which is more relevant to typical human exposure. Other hazardous substances are also interesting to study.
”We want to identify the bad guys - the substances that are most dangerous for the male germ cells," says Olsen.
Olsen AK et al Environmental exposure of the mouse germ line: DNA adducts in spermatozoa and formation of de novo mutations during spermatogenesis. PLoS One, 2010 June 28;5 (6): e11349
Studies from Denmark
Mamsen LS et al. Mamsen LS et al Cigarette smoking during early pregnancy reduces the number of embryonic germ and somatic cells. Hum Reprod 2010, Sept 7, electronic publishing.
Lutterodt MC et al The number of oogonia and somatic cells in the human female embryo and foetus in relation to whether or not exposed to maternal cigarette smoking. Hum Reprod 2009; 24 (10): 2558-66.