July 5, 2007 Exposing a developing female sheep fetus to low doses of chemicals commonly present in the environment can disturb the development of the ovary, a scientist told the 23rd annual conference of the European Society of Human Reproduction and Embryology (Wednesday 4 July). Dr. Paul Fowler, of the University of Aberdeen, Scotland, UK, said that this research would help to establish the importance of the effect of environmental chemicals for fertility.
Over recent decades there has been a dramatic increase in the production of industrial and agricultural chemicals and heavy metals, and this has coincided with widespread reports of breeding problems in wild animals. Fertility also appears to be declining among humans and there has also been a rise in reproductive defects observed in newborn babies.
Until now, most studies have looked at a short-lived exposure to high doses of single compounds, and have usually done so in mice and rats. Dr. Fowler and his colleagues decided to study the effect of long-term, low-level exposure to a cocktail of chemicals and heavy metals in an animal which has a long pregnancy, therefore better replicating the situation in the human.
"Our 'real life' model exposed developing sheep fetuses by pasturing their mothers on fields fertilised with either inorganic fertiliser, the control group, or, in the case of the treatment group, with digested human sewage sludge, before and during pregnancy", said Dr. Fowler.
" We examined the ovaries from the fetuses at day 110 of gestation, the equivalent of week 27 in a human pregnancy, and found that the ovaries from the fetuses where the mother was grazing the sewage sludge fields contained fewer eggs and also a number of protein abnormalities. These differences could have implications for problems such as cancer in later life."
The scientists hope that their Wellcome Trust-funded study will help to pinpoint the stages of pregnancy at which the developing fetus is most sensitive to disruption and also to measure the degree to which fertility is affected in the offspring after puberty, following their exposure as fetuses to environmental concentrations of a mixture of pollutants. "Switching some mothers from sewage sludge fertilised to control pastures before conception will tell us whether maternal exposure either before or during pregnancy does most damage to the offspring", said Dr. Fowler. "The sheep model is quite novel, with relatively little research in the area currently being performed in this way. One of the collaborators in the project, Professor Richard Sharpe from the MRC Human Reproductive Sciences Unit in Edinburgh, UK, has already found reduced testosterone and testis cell numbers in the male fetus exposed to sewage sludge at day 110 of gestation.
The group has applied for further funding to look more closely at the implications of the sheep findings for humans, for instance by comparing quantities of chemicals in the human fetus with those seen in sheep, and investigating whether changes induced in the sheep fetus could be a problem for the developing human. They also intend to look at the mechanisms by which exposure to environmental chemicals can cause defects in reproductive development in order to determine what might be done to reduce risks for the human fetus.
There is still considerable debate around the level of importance of environmental chemicals in cancer, obesity, infertility and other complex diseases which have multiple causes. "We hope our research will help in the drive for evidence-based policy making on this issue", said Dr Fowler. "If we can definitely establish that environmental chemicals are important in triggering these diseases, then we might be able to produce better treatments, but it would also be important to devise legislation to begin reducing the levels of such chemicals. We would then look to work with chemical and agricultural industries to find safer chemicals by improving how they assess fetal development effects. If such measures helped to reduce the rates of cancer, obesity and infertility, there would be considerable benefits in terms of the costs of healthcare."
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