Does exposure to mercury, lead, and other heavy metals affect women’s reproductive health? Intramural Research Training Award Postdoctoral Fellow Anna Z. Pollack, Ph.D., gained vital research skills during her time at the NICHD working to answer that question.
Dr. Pollack was interviewed about her experiences as an NICHD postdoctoral fellow in the summer of 2013. She has since left her fellowship to become an assistant professor at George Mason University, in Virginia.
As an NIH postdoctoral fellow, Dr. Pollack worked in the Epidemiology Branch of the Division of Intramural Population Health Research, formerly the Division of Epidemiology, Statistics, and Prevention Research, where she investigated women’s exposure to heavy metals, and whether that exposure has an effect on their long-term health.
Q: You’re a postdoctoral fellow, sometimes called a “postdoc,” at the NICHD. What does that mean?
Dr. Pollack: What that means is, I’ve finished my Ph.D., and now I am working with a mentor here in the Epidemiology Branch to further my own research career. I actually started here in the Epidemiology Branch as a summer student, after I received my master’s degree. I later became a predoctoral fellow [before getting a Ph.D.]. I actually did my Ph.D. dissertation here as well, and then transitioned to a postdoctoral fellowship, which has been a wonderful and very enriching experience.
Q: What’s the purpose of doing a postdoctoral fellowship? Once you have your doctorate, isn’t that enough training to start your own research career?
When I was starting my Ph.D., I thought, “Oh, I'll certainly not do a postdoctoral fellowship. I want to get right into research and become an independent investigator.” But the value in doing a postdoc is that you have protected time to build your own research and to better understand how to publish papers, how to apply for grants, how to collaborate with other investigators on their projects. You become more skilled at developing your own research proposals, writing papers, and mentoring other people yourself, which are all important skills. When you’re an independent investigator, you don’t have the luxury of as much time to get those skills up and running. It’s been a very valuable experience, having a postdoctoral fellowship.
Q: Has mentoring been a big part of your experience at NIH?
As a postdoctoral fellow, you’re on both sides of the mentoring equation. I am mentored by Dr. Enrique Schisterman, who is our Branch Chief and is a senior investigator in the Epidemiology Branch here at NICHD. When I was a predoctoral fellow, I met with him much more regularly to go over the “nuts and bolts” of how to approach a certain paper and how to think about the analysis. If I was going to give a poster or a talk at a conference, I would meet with him repeatedly in order to practice my talk, practice presenting my poster. Since I’ve been here for a few years in my postdoctoral fellowship, I also had the opportunity to mentor a summer student, and that was a great experience. I actually took a course on mentoring that’s offered here at NIH through the Office of Intramural Training and Education. That was very helpful when I mentored my student this past summer. I worked with her to develop her own independent research, which we’re currently working on publishing.
Q: It’s part of the scientific “tradition,” isn’t it, to have and be a mentor?
Yes, and it’s a great thing about science that you can keep these mentors from various facets of your life as you move forward. So it’s helpful.
Q: Do you work in a lab?
In epidemiology, we talk about ourselves as having “labs,” but it really doesn’t look the same way it looks on what we call the main campus of NIH. We work in a suburban office building, and I spend a lot of time in front of my computer doing work day to day.
Q: What is your research area of expertise?
I have been focusing on reproductive epidemiology, which is the study of health in populations of people. In my particular area, I focus on women’s health, and I have worked some on understanding reproductive hormones in the menstrual cycle in relation to certain environmental exposures. I’ve done some other work, more recently, on female gynecological disease, including a condition called endometriosis and another condition called uterine fibroids. Those are two very prevalent conditions in women of reproductive age.
Q: How did you get interested in the area?
Initially, I was interested in chemicals called endocrine disruptors, that is, chemicals that affect the way the hormones in your body work. I’ve been interested in these chemicals since I was an undergraduate, and I had the opportunity to do some research with Dr. Sandra Petersen [of the University of Massachusetts, Amherst]. We were looking at this chemical called dioxin, which is a potent endocrine disruptor. We were working in animal models at that time, and I was interested in health in populations of people. My interest in how chemicals could affect hormones transitioned into human health effects, and that’s been my interest since then.
Q: Let’s talk a little bit about the BioCycle Study, because I think that’s the data you’ve been working on.
Sure. The BioCycle Study is a study that was done between 2005 and 2007 in upstate New York. They recruited 259 healthy premenopausal women who volunteered for this fairly rigorous study. They were interested in looking at the interplay between the women’s hormones and biomarkers of oxidative stress, and understanding that relationship.
My mentor, Dr. Schisterman, undertook the BioCycle Study in order to better understand that interplay. The research participants were wonderful in their effort. They came into the clinic up to eight times per menstrual cycle, for two cycles. They had to give blood and urine samples at each clinic visit, so it was no small thing that they were volunteering for. That's been a very rich resource to use since then.
Q: Can you just explain what a biomarker is and what oxidative stress is?
Sure. By biomarker, I mean there’ll be components of those exposures that we can measure in either blood or urine. What we’re looking for is evidence of these chemicals in urine samples.
The reason people take antioxidant vitamins and use antioxidant skin creams and lotions is to fight oxidative stress, which can harm the body. It has been thought that reproductive hormones worked to decrease oxidative stress, but that relationship wasn’t ever fully understood.
Q: The BioCycle Study was a collaboration between investigators from the NICHD and from the University of Buffalo. Is it unusual to work with outside investigators?
The way research is done on the intramural side of the Epidemiology Branch is that tenure-track investigators will design a research project. Then, they work with outside groups, which would be either universities or companies, that can then put that project into place and carry out that research project. This was done through a collaboration with the State University of New York at Buffalo.
So as you can imagine, getting 259 women into eight clinic visits and recruiting them for research is not an inexpensive undertaking. It’s important that the study be available as a resource for additional projects. The BioCycle Study was forward-thinking in that way. Biospecimens—blood and urine—were banked so that investigators could later launch their own projects and look at different hypotheses.
For my dissertation work, I was interested in how common metal exposures may affect reproductive hormone levels. Metal exposures come from a variety of sources, and it’s something to which we’re all exposed at very low levels. Cadmium, lead, and mercury are the three metals that I was interested in.
As you may know, mercury exposure largely comes from fish consumption. Elemental mercury is released from, commonly, coal-fired power plants. Then, that elemental mercury is deposited into the water and is changed by bacteria into what’s called methylmercury. It follows up the food chain, so that’s why these larger fish, like shark and swordfish, are two fish that have very high mercury concentrations. That’s because they’re at the top of the food chain. Those two fish have very high mercury levels.
Although all of us have some low-level exposure to cadmium, that’s largely through diet. Various shellfish have high levels of cadmium, including my favorite, blue crab. In addition, cigarette smoking is a primary source of exposure to cadmium.
In terms of lead, exposure comes from lead paint, which is no longer in use, of course; but in older homes, dust from those lead paint chips can be a source of exposure. In the United States, we no longer have leaded gas, so that’s not a source of exposure here. But in many developing countries, leaded gas continues to be used, so that continues to be a significant source of exposure. In addition, here in the D.C. area, as some people may be aware, there are some water pipes that contain lead. Depending on where you live, that could be an additional source of lead exposure.
Q: What studies have you done on each of these metals, and what have you found?
Most of my work, ideally, should be “null,” meaning that I should find nothing. I’m looking at people who are healthy, who are not exposed from their occupation, which we would expect to give them higher levels of exposure. As we would expect, many of my findings have been null, which is rather comforting.
We wanted to know whether cadmium, lead, and mercury were associated with increased biomarkers of oxidative stress. We actually found no association. Interestingly, I saw that with increased mercury exposure, one biomarker of oxidative stress decreased. That was interesting because we thought, “While these metals are probably bad for you, why would we see a decrease in this one biomarker of oxidative stress?” If you remember, one of the most common sources of mercury is fish consumption. But fish consumption is also very good for you. There are important fatty acids that come from fish consumption. We think that what was going on there is, mercury increased with fish consumption, but it was also an indicator of the healthful effects of fish consumption.
Some of our findings were below levels of public health concern. At low levels of lead, we saw some increases in progesterone levels, which is a reproductive hormone in women. I’ve also seen some decreases in follicle stimulating hormone, which is another reproductive hormone in women, with increasing cadmium exposure.
Q: But you don’t know what happens over years and years of exposure, is that right?
Sure. The BioCycle Study, because it was so intensive, we don’t have the luxury of understanding how this plays out over long periods of time. The study was only able to follow the women for two menstrual cycles. While we have very good data over about a 2-month period for these women—which can help us understand whether or not there’s interactions on a month-to-month basis—we don’t know if these could become chronic health issues.
Q: You also looked at bone density and heavy metals in premenopausal women, correct?
Right. Another project that I worked on was looking at these three metal exposures, cadmium, lead, and mercury, in relation to bone mineral density. In older populations and post-menopausal women, other studies have seen that cadmium is associated with decreased bone mineral density. Actually, in areas with very high cadmium exposure, there is a clear association between poor bone mineral density and cadmium exposure. But less was known about whether or not these associations could be seen in premenopausal women, in populations that are exposed to levels of cadmium to which we would all be exposed.
I was able to look at that [using data from] the BioCycle Study. What we found in that study was that actually, cadmium, lead, and mercury were not appreciably associated with bone mineral density, which is, as I was saying earlier, comforting because these are levels to which all of us are probably exposed. These were young, healthy, premenopausal women. If we were seeing effects on bone mineral density in young healthy women, at levels to which we’re all exposed, that would really be concerning. It was somewhat reassuring that I didn’t find positive associations in that study.
Q: Is that the ultimate goal, to figure out what can we handle, as human beings, in terms of exposure to these metals?
Certainly. With respect to cadmium, lead, and mercury, these are three naturally occurring elements to which we all have some level of exposure. It’s not likely that we could ever completely rid ourselves of exposure to these metals, so it’s important to understand where the safe levels lie. Interestingly enough, all of the women in the BioCycle Study are below the Centers for Disease Control and Prevention levels of concern [for exposure], particularly so with lead. That we’ve seen some health effects does raise the question of those levels. Understanding that perhaps health effects may even occur below those [exposure] levels [set by the government] is, I think, important.
Q: What were your findings related to caffeine in pregnant women?
The study that I did on caffeine exposure and miscarriage, I did while I was a summer student. I was interested in understanding whether caffeine consumption could be associated with pregnancy loss. There’s been a lot of work in this area, and it seems to be conflicting. While there are fairly universal recommendations that pregnant women not consume vast quantities of caffeine, there’s still varying degrees to which people recommend curtailing caffeine use during pregnancy.
We found that there was no association between moderate caffeine intake and pregnancy loss. That was in conflict with some other studies that had come out around that same time, but it was such that we felt comfortable in that paper that there were no associations between moderate levels of caffeine consumption and pregnancy loss.
Q: You want to become an independent investigator?
Certainly, yes. My goal, after my postdoctoral fellowship is finished, is to become an independent tenure-track investigator. Ideally, what I’d like to do is to be an assistant professor on the tenure track at a university that focuses both on research and teaching.
[Note: Dr. Pollack is now an assistant professor at George Mason University, in Virginia.]
Q: I know you’re early in your career, but do you ever think about, when you get to the end of your career, what you want to have accomplished?
Sure. I think, over the course of my career, what drives me is to understand how chemical exposures, to which we’re all exposed, how those might affect our everyday health. I think that by the end of my career, what I want to have understood is some of those exposures, whether some of those exposures are safe, or whether there are some ways to which we can reduce our exposure to some of those chemicals, whether it’s through changing some practices, or whether that’s through some efforts at changing regulations and changing the availability of those products in general.