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Vinclozolin is a fungicide that is sprayed on crops, turf, and ornamental plants in Maine and across the country to control mildew and fungus problems like black spot. It is used not only by farmers, but by householders and gardeners as well. Yet it may have serious consequences for the offspring of mothers exposed to the fungicide during pregnancy.
Vincent Markowski, assistant professor of psychology, is studying the effect of prenatal maternal exposure to toxic environmental substances such as vinclozolin and dioxin on reproductive behavior and cognitive processing in offspring. Markowski, one of the first group of USM faculty to receive appointments at our Bioscience Research Institute of Southern Maine (BRISM), is using BRISM funds to study the effects of environmental toxicants on prenatal brain development.
Markowski has been studying the impact of dioxin on prenatal
development for the past six years. Dioxin is an endocrine
disrupter, which is an agent that influences hormone function.
Markowski and colleagues at the University of Rochester, where
he held a post-doctoral appointment before coming to USM in
the fall of 2000, have concluded a series of dioxin studies
that will be published later in 2002. He is shifting his research
focus now to vinclozolin because more is known about the biochemical
pathways of the fungicide in humans, he says. His research
on vinclozolin will have implications for humans.The EPA has
looked at the impact of vinclozolin on reproductive organs
but not on brain development, so Markowski's research will
fill a gap in the existing knowledge of this compound.
The pilot studies on vinclozolin he's conducting now, made
possible by BRISM funding, will enable Markowski to determine
the quantity of vinclozolin he should administer in experiments
and demonstrate that his techniques are feasible, allowing
him to compete for federal funding. While vinclozolin degrades
quickly, it breaks down into two metabolites that persist
and can be ingested or absorbed by humans from plants.These
metabolites bind to androgen receptors, complex proteins to
which hormones like testosterone bind. The vinclozolin metabolites
interfere with the role testosterone normally plays in developing
male reproductive organs and certain regions of the brain.
Androgen receptors, for example, are found in high concentrations
in regions of the brain that control sexual behavior. One
hypothesis Markowski is testing is that in utero exposure
to vinclozolin may cause fewer neurons to develop in these
regions.
Migrant workers who work in fields sprayed with vinclozolin may be at risk, but also anyone who eats plants treated with the fungicide. In humans, the typical route of exposure, Markowski says, would be oral.
Markowski has designed experiments with rats to test his hypothesis. He feeds
a daily dose of vinclozolin to a number of pregnant females,
producing litters of rats that have been exposed in utero
to amounts of the fungicide equivalent to what human fetuses
would be exposed to if their mothers ate food plants treated
with it. The fungicide doesn't cause toxicity in the pregnant
females ingesting it, but the developing brains of the offspring
are so sensitive that the research does not require high doses
to produce effects. He raises and tests the black and white
hooded rats in the laboratories that BRISM rents on John Roberts
Road in South Portland.
In his lab, rats are placed in operant conditioning boxes and are trained to press levers on a specified schedule to release food pellets. Male rats tend to learn how to operate the levers more quickly than females because of the role testosterone plays in brain development, Markowski explains. The rats continue the operant conditioning over two to three months and are tested five days a week for their efficiency, demonstrated through the number of errors and quantity of food pellets they are able to release. Markowski and his undergraduate assistants collect the data and run it through a computer analysis. Ultimately, they will compare the learning efficiency of male and female rats exposed to vinclozolin to that of rats in control groups. The experience students gain by working with rats on actual experiments brings alive the theories they learn in psychology classes. The operant conditioning box, for example, was originally developed by famous Harvard professor B.F. Skinner, whose work has been read by generations of psychology majors.
In addition to the learning tests, Markowski’s lab also examines other sex-linked behaviors, including social play in juvenile rats, penile erections in adult rats, and stress hormone responses in both juveniles and adults. All of these behaviors are sensitive to exposure to environmental compounds that alter the structure or function of the spinal cord, hypothalamus, or neocortex.
Markowski and two colleagues at Bates College who are collaborating with him on the research are applying for an AREA grant from the National Institute of Environmental Health Sciences that will be based on the preliminary results from the pilot study funded by BRISM.
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