Studies probe method to curb Parkinson’s disease and causes of infertility
Three studies led by Dr. Hugh S. Taylor of Yale School of Medicine were presented
at the 2008 Society for Gynecologic Investigation (SGI) Annual Scientific Meeting
held March 26-29 in San Diego, California.
One of the studies looked at a new approach for curbing Parkinson’s disease,
another focused on the link between in utero exposure to a hormone that controls
appetite and decreased fertility, and a third examined how synthetic estrogens
affect the reproductive system.
Curbing Parkinson’s disease
The injection of uterine stem cells trigger growth of new brain cells in mice
with Parkinson’s disease, reported Yale School of Medicine researchers
“Previously, we were able to coax these multipotent stem cells to differentiate
into cartilage cells,” said Taylor, professor in the Department of Obstetrics,
Gynecology & Reproductive Sciences and section chief of Reproductive Endocrinology
and Infertility at Yale School of Medicine. “Now we have found that we
can turn uterine stem cells into neurons that can boost dopamine levels and partially
correct the problem of Parkinson’s disease.”
Parkinson’s disease is a degenerative disorder of the central nervous
system that often impairs the sufferer’s motor skills and speech. The
primary symptoms are the results of decreased stimulation of the motor cortex
by the basal ganglia, which is normally caused by the insufficient formation
and action of dopamine.
The stem cells in this study were derived from human endometrial stromal cells
that were cultured under conditions that induce the creation of neurons. These
cells then developed axon-like projections and cell bodies with a pyramid shape
typical of neurons.
“The dopamine levels in the mice increased once we transferred the stem
cells into their brains,” Taylor said. “The implications of our findings
are that women have a ready supply of stem cells that are easily obtained, are
differentiable into other cell types, and have great potential use for other
Other authors include Dr. Erin Wolff, who presented the abstract at SGI, Zane
B. Andrews, Xiao-Bing Gao
and Katherine V. Yao. This abstract was an SGI Trainee Plenary Session Selection
and winner of the SGI President’s Presenter Award.
Synthetic estrogens and fertility
Researchers at Yale School of Medicine now have a clearer understanding of
why synthetic estrogens such as those found in many widely-used plastics have
a detrimental effect on a developing fetus and cause fertility problems, as
well as vaginal and breast cancers.
Past research shows that exposure to the synthetic estrogen diethylstilbestrol
(DES) alters the expression of HOXA 10, a gene necessary for uterine development,
and increases the risk of cancer and pregnancy complications in female offspring.
The team led by Taylor sought to understand why a developing female fetus exposed
to DES might develop uterine cancer and other problems years after exposure.
Even though DES is no longer on the market, the authors chose to study its
effects to gain insight into how similar synthetic estrogens might work.
The team studied DNA from the offspring of 30 pregnant mice injected with DES.
They found changes in certain regions of the HOXA 10 gene. These alterations
continued beyond the time of development and persisted into adulthood, indicating
that exposure to DES and similar substances results in lasting genetic memory,
known as “imprinting.”
“We found that HOXA 10 protein expression was shifted to the bottom portion
of the uterus in the female offspring,” said Taylor. “We also found
increased amounts of the enzyme responsible for changes in the DNA. Rather than
just changing how much of the protein is there, DES is actually changing the
structure of the HOXA 10 gene.
“These findings bring us closer to understanding the way in which DES interacts
with the developing reproductive system,” said Taylor.
Pregnant women are frequently exposed to other similar substances with estrogen-like
properties, such as Bisphenol-A (BPA). BPA is found in common household plastics
and has recently been linked to long-term fertility problems. Like DES, these
other substances may also impact female reproductive tract development and
the future fertility of female fetuses.
Other authors on the abstract included Jason Bromer, who presented the abstract,
and Jie Wu. This abstract was an SGI Trainee Plenary Session Selection and
winner of the SGI President’s Presenter Award.
Hunger-inducing hormone and fertility
Researchers at Yale School of Medicine have found that in utero exposure to
the hormone ghrelin, a molecule that controls appetite, hunger and nutrition,
can result in decreased fertility and fewer offspring.
Ghrelin, the so-called “hunger hormone,” is produced in the stomach
and brain, induces food intake, and operates through a brain region that controls
cravings for food and other energy sources. Ghrelin decreases the HOXA 10 gene
that is involved in developmental programming of the uterus. The HOXA 10 gene
determines how the uterus will develop in adulthood.
“When you’re obese, ghrelin levels are lower, and based on these
preliminary findings, they may result in lower fertility,” said Taylor.
The researchers bred mice designed to be deficient in ghrelin production. These
mice had offspring with decreased fertility and that produced smaller litter
sizes. These offspring also had lower expression of the HOXA 10 gene, which
is important for proper development of the uterus in the embryo. In the adult
uterus, it maintains the ability of the uterus to provide an optimal environment
for proper development of the embryo.
“Obesity may have an effect on pregnancy in the next generation,” said
Taylor, adding that the findings underscore the importance of nutrition, energy
utilization and appropriate ghrelin levels on normal uterine development. Taylor
and his team will next study the effects of lower ghrelin levels on humans.
Other authors include Amy Tetrault, who presented the abstract at SGI, Sarah
Lieber, Marya Shanabrough and Tamas Horvath.
— By Karen Peart
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