By Greg Anderson

This post highlights some excellent recent work published by MBP student Monique Rennie at the Mouse Imaging Centre (MICe). The full article is published as Rennie et al., Am J Physiol Heart Circ Physiol 300: H675-H684, 2011.

At least once a day, I find myself in a state of shock-and-awe as I witness someone my own age or younger smoking a cigarette. For some reason, this is more surprising to me than, say, a 60-year old man smoking. It's not as though anyone born post-1980 doesn't know about the dangers of smoking; it's been drilled into our heads from a very young age. Yet the habit persists. Maybe not as many people smoke now as opposed to 1960, but still, the tradition lingers. And now, here to shed more light on the dangers of pre-pregnancy smoking comes new research conducted by members of the Medical Biophysics department.

Polycyclic aromatic hydrocarbons (PAHs) are the main toxic components of cigarettes, in addition to being common environmental pollutants. The negative effects of PAHs on growing fetuses is perhaps their most devastating feature: exposure can lead to fetal growth restriction, reduced fetoplacental blood flow, and a whole host of other morbidities. So while the proportion of women who smoke during pregnancy has dramatically decreased in recent decades, it turns out that this may not be enough. You see, PAHs have the uncanny ability to accumulate in both adipose and mammary tissue of smokers, thus allowing the toxic chemicals to be released into the blood stream during pregnancy. However, there is a scarcity of information on the actual effects of PAH accumulation on pregnancy outcomes in the literature. Thus, Monique and her team set out to try to get to the bottom of some of these nagging questions, using some very sophisticated and novel imaging techniques. "This is a fantastic paper (not to toot my own horn), because those who care only about imaging physics will find it interesting just as much as those who only care about the biological effects of smoking on pre-pregnancy fetuses will" says Monique (after being cornered by yours truly).

Using micro-computed tomography (micro-CT) and some novel vessel tracking software developed by Dr. John Sled, Monique has shown that it's possible to image the growing vasculature of the placenta and to quantify many physical characteristics of these blood vessel trees. In fact, using this vessel tracking software, the number, physical dimensions, and physical characteristics (such as blood pressure) of the developing placental vasculature can be accurately determined. This is an extremely important step in the field of developmental biology, as it allows this field to rely less on qualitative, descriptive science and turns it into a more quantitative and numbers-driven science. As well, the ability to manipulate these vascular trees in 3 dimensions is extremely advantageous, as questions of form and function can now begin to be answered.

Mice in this study were injected with either corn oil (control) or PAHs over a 9-week period to simulate smoking the equivalent of 7 cigarettes a day in humans. Following the last PAH administration, the female mice were then mated with normal male mice, and their fetuses were dissected at embryonic day 15.5 (this is close to the end of pregnancy; most mice have a gestation period of approximately 18-20 days). Following micro-CT analysis, some extremely interesting results were obtained. Compared to control mice, the PAH-treated mice had placental vasculatures that were normal in size (i.e. the span and depth), but that had a 27% reduction in the number of arteriole-sized blood vessels within the vascular tree. The absence of this vast a number of arterioles in the vascular tree led to a subsequent 30% increase in fetoplacental arterial vascular resistance (which is very harmful to the developing fetus as it corresponds to a 19% decrease in umbilical blood flow), as well as leading to an increase in tortuosity of the vascular tree itself. Both of these factors contribute to fetal weight restriction. What would be interesting to see is how the pups born of these PAH-treated mothers would respond to cognitive tasks later in life.

So there you have it: even quitting smoking before becoming pregnant can have dire consequences on the health of unborn children. Using sophisticated, in-house generated computer algorithms, Monique has been able to show that PAHs can negatively affect the placental vasculature not by necessarily changing its size, but by causing it to become more sparse, thus leading to increased vascular resistance. As an imaging paper, this study helps transform developmental biology into a more quantifiable and definitive science (as well as providing biologists with images that truly make one say, "wow"); as a biological paper, this study sheds even more light onto the devastating side-effects of smoking by providing clear, quantitative results. Truly this is the type of work that defines "medical biophysics", and reflects the unique nature of our department. As if anyone needed more reasons to quit smoking, now we're reminded of Helen Lovejoy's' famous Simpsons quote: "Won't somebody please think of the children!?"