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Research Project
The focus of my research within the Molecular and Genomic Toxicology
Laboratory at Michigan State University is male endocrine disruption
by estrogen-like chemicals using a mouse model system.
Several natural and synthetic chemicals including pharmaceuticals,
nutriceuticals,phytoestrogens, pesticides, environmental pollutants
and industrial chemicals are known to posses distinct estrogen-like
properties and have been examined by our laboratory. My particular
investigation will address the effect of the phytoestrogen,
genistein, on male reproductive development and fertility in
mice.
Genistein is an isoflavone found in unfermented soy products.
As a phytosteroid, genistein "imitates" estrogen considering
that genistein may compete for estrogen receptors. Genistein
may bind to the estrogen receptor without eliciting a large
estrogenic response and may therefore inhibit the stronger endogenous
estrogenic agonists from binding. Coincidentally, genistein
has also been reported to reduce circulating levels of the gonadotrophic
hormone, LH, which is crucial in the regulation of steroidogenesis
and subsequent spermatogenesis and secondary sex characteristics
of males.
The objective is to examine the effect of genistein at distinct
reproductive end points in the male mouse at the molecular,
cellular and tissue levels. Molecular investigations will feature
a testis specific microarray application developed in our laboratory
while cellular and tissue level data will include measures of
sperm analysis, in vitro fertilization and testis histology
respectively.
Furthermore, other potential endocrine disrupting chemicals
will be examined for estrogen-like activity including genistein,
diethylstilbesterol, and zearalonone. The estrogen-like activity
of these chemicals will be assessed taking advantage of the
unique estrogen-inducibility of vitellogenin. Vitellogenin is
a serum phospholipoglycoprotein precursor to egg yolk in ovoviparous
organisms. In vertebrates, estrogen induces vitellogenin in
the liver which is then secreted into the bloodstream and taken
up by oocytes and is not expressed in the male of the species.
Coincidentally, vitellogenin expression has been found to be
an excellent biomarker for exposure of males to estrogenic substances.
A quantitative competitive reverse transcription-polymerase
chain reaction (RT/PCR) will be used for analysis of vitellogenin
mRNA standardized to beta-actin.
Curriculum Vitae
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