Smoking while pregnant affects the development of the ovaries in a woman's girl children.

What is it about?

When a woman continues to smoke cigarettes when pregnant there is a much greater chance that her offspring will be born with defects or will have less good health as a child and adult. There are many examples, including increased risk of being born small, having asthma or poorer school performance and also reproductive problems, such as reduced fertility. The mechanisms involved are not well understood. One reason for this is that it is, not surprisingly, very difficult to study the developing human fetus in the womb. We solve this by studying fetuses which are terminated for non-medical reasons. By measuring metabolites of nicotine in the fetus itself we can be sure whether the mother smoked cigarettes, or was exposed to a lot of second hand smoke, while pregnant. We studied ovaries from fetuses between 11 and 20 weeks of gestation and compared those exposed to cigarette smoke in the womb with those which were not. If the mother smoked, the fetus had higher levels of the female sex hormone, oestrogen. Within the ovary itself, the development of structures called follicles, which surround the eggs was disturbed in smoke-exposed fetuses. Some of the negative outcomes were consistent with effects driven by a class of contaminating chemicals that are found in cigarette smoke and in air pollution - polycyclic aromatic hydrocarbons. We found that the signals between cells needed to allow the construction of the follicles, and protection of the egg,s became uncoordinated in many of the fetal ovaries if the mother smoked.

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Why is it important?

Our unique study shows that if a women continues to smoke while pregnant, her girl children will have high oestrogen levels and uncoordinated development of her ovaries. This is partly driven by messages between chemicals in cigarette smoke and signals within the ovary that control normal development. As a consequence the offspring is more likely to be born with a smaller number of eggs enclosed within structures called follicles. These represent her reproductive capacity and as a consequence sh is more likely to be less fertile or have an earlier menopause. We already know it is very bad for children if their mother continued to smoke while pregnant with them. What our study adds is a better mechanistic understanding of how chemicals in cigarette smoke (some are also in air pollution) can disturb normal development in the human. This may provide insights into strategies to reduce damage from such chemicals.

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