From the Special Topic of
According to our Special Topics analysis on Epigenetics
research over the past decade, the paper "Epigenetic
transgenerational actions of endocrine disruptors and male
fertility" (Anway MD, et al., Science 308:
1466-9, 3 June 2005) is a key paper in the Research Front
Epigenetic Gene Regulation. The paper, written by Dr.
Michael Skinner and his team of research fellows at
Washington State University, has 234 cites to its credit
for the period ending October 31, 2008 in
Essential Science IndicatorsSM from
Dr. Skinner is a professor in the School of Molecular Biosciences at
Washington State University. He also established two research centers
there: the Washington State and University of Idaho Center for Reproductive
Biology and the Center for Integrated Biotechnology. He served as the
director of these centers for many years, but stepped down in 2008 to
concentrate more on his own research efforts.
His record in our database includes 91 papers, the bulk of which are
classified in Biology & Biochemistry, cited a total of 2,345 times.
This month, ScienceWatch.com
talks to Dr. Skinner about the paper and its impact
on the field.
Would you please describe the significance of
your paper and why it is highly cited?
In our paper, we were exploring whether exposure to environmental compounds
such as endocrine disruptors (either the anti-androgenic fungicide
vinclozolin or the estrogenic pesticide methoxychlor) during gestation in
rats would result in decreased spermatogenic capacity and increased male
infertility in the next generation. Although only the original generation
mother was exposed to the compounds, we observed these effects in nearly
all males of all the subsequent generations studied (up to four
Subsequent studies have demonstrated effects on a wide variety of adult
onset disease states. The idea that environmental factors could
epigenetically reprogram the germ line in this fashion was a novel idea for
how environmental factors may influence disease etiology. In essence, what
your grandmother was exposed to when she was pregnant may cause disease in
you and your grandchildren.
How did you become involved in this research, and
were there any particular successes or obstacles that stand
"It will be important to determine
what other disease states can come about
through epigenetic effects of environmental
I did my B.S. in chemistry at Reed College in Portland, Oregon, my Ph.D. in
biochemistry at Washington State University, and my postdoc at the C.H.
Best Institute at the University of Toronto. Prior to returning to
Washington State as a professor, I was on the faculty of Vanderbilt
University in Nashville, Tennessee, and the University of California, San
My research focuses on exploring the manner in which different cell types
in a tissue interact and communicate to regulate the growth and
differentiation of gonads. We were investigating the effects of the
environmental compounds on gonadal sex determination and serendipitously
found these epigenetic transgenerational effects on adult onset disease.
Where do you see your research and the broader
field leading in the future?
The broader direction is determining the role of epigenetics in disease
etiology and how environmental factors can promote adult onset disease and
alter biological processes. Because the doses of the endocrine disruptors
in our study were higher than levels occurring in the environment, we need
to employ dose curves and toxicology studies to see if environmental levels
also cause these transgenerational effects. We also need to test other
compounds for their potential epigenetic transgenerational effects. The
current focus is elucidating the molecular mechanisms involved in
reprogramming the germ line and transgenerational nature of the phenomena.
It will be important to determine what other disease states can come about
through epigenetic effects of environmental factors.
What are the implications of your work for this
These results have implications for toxicology, evolutionary biology, and
the molecular basis of heritable disease. With regard to toxicology, we
showed that the potential danger of environmental toxicants known as
endocrine disruptors could have a long-lasting, transgenerational effects.
Secondly, we also demonstrated that an environmental factor could trigger
an epigenetic change to a genetic trait, which impacts our view of
evolutionary biology. Thirdly, there were implications that events in
embryonic and fetal development can affect disease states in adults.
Epigenetics will be a critical process involved in how environmental
factors influence biological processes and disease.
Michael K. Skinner
Center for Reproductive Biology
School of Molecular Biosciences
Washington State University
Pullman, WA, USA
Keywords: EPIGENETIC TRANSGENERATIONAL ACTIONS; MATERNAL
CARE EFFECTS; EPIGENETIC GENE REGULATION; EPIGENETIC DIFFERENCES
ARISE; EPIGENETIC PROGRAMMING.