Component in Soy Products Causes Reproductive Problems in
Laboratory Mice
From NIH
News - National Institutes of Health
January 10,
2006
Genistein,
a major component of soy, was found to disrupt the development of the
ovaries in newborn female mice that were given the product. This study
adds to a growing body of literature demonstrating the potentially
adverse consequences of genistein on the reproductive system.
“Although
we are not entirely certain about how these animal studies on genistein
translate to the human population, there is some reason to be
cautious,” said Dr. David A. Schwartz, Director of the National
Institute of Environmental Health Sciences (NIEHS). “More
clinical studies are needed to determine how exposure during critical
windows of development can impact human health.”
Genistein
is the primary naturally occurring estrogen in plants (called
phytoestrogens) and can mimic the effects of estrogen in the body.
Genistein can be found in foods containing soy such as soy-based infant
formulas as well as over-the-counter dietary supplements.
The results
of this study conducted by researchers at the National Institute of
Environmental Health Sciences (NIEHS), part of the National Institutes
of Health, in collaboration with an investigator at Syracuse
University, are published in the January issue of Biology of
Reproduction.
The NIEHS
researchers previously showed that mice given genistein immediately
after birth had irregular menstrual cycles, problems with ovulation,
and problems with fertility as they reached adulthood. The new study
looks at the direct effects of genistein on the ovaries during early
development.
“We
knew genistein was linked to reproductive problems later in life, but
we wanted to find out when the damage occurs,” said Retha R.
Newbold, MS, a developmental endocrinologist at NIEHS and an author on
the study. “The study showed that genistein caused alterations to
the ovaries during early development, which is partly responsible for
the reproductive problems found in adult mice.”
Female mice
were injected with three different doses of genistein during their
first five days of life. The genistein given to the mice was comparable
to what human infants might receive in a soy-based formula, which is
approximately 6-9 mg/kg per day. The researchers examined the effects
on days 2 through 6.
The
researchers found effects at all levels. Mice treated with the high
dose (Gen 50 mg/kg) were infertile and mice treated with lower doses
were subfertile, meaning they had fewer pups in each litter, and fewer
pregnancies. Mice receiving the highest level of genistein, 50 mg/kg
per day, had a high percentage of egg cells that remain in clusters,
unable to separate and therefore develop abnormally. The researchers
explain that oocytes that remain in clusters are less likely to become
fertilized based on previous research. The largest difference between
the genistein treated and normal mice was found at six days of age
where 57 percent of the egg cells in the non-treated ovaries were
single or unclustered; and only 36 percent in the genistein treated
group were single.
We think
genistein inhibits the oocytes or egg cells from separating
apart,” said Wendy Jefferson, Ph.D. of NIEHS and lead researcher
on the paper. “Since there are many egg cells in the same
follicle instead of just one, the resources from the surrounding cells
are spread too thin and they can’t get the support they need to
become a mature functioning egg cell.”
“You
need at least one good healthy single oocyte that is ovulated and
fertilized by a sperm to get a healthy baby. Genistein seems to have a
way of making this task very difficult,” said Newbold.
“I
don’t think we can dismiss the possibility that these
phytoestrogens are having an effect on the human population,”
said Dr. Jefferson. “They may not show their effects or be
detected until later in life, but chances are they are having an
effect.”
Figure
1, alt text: This illustration depicts normal egg cell
development in mice as shown in the top. The bottom image shows the
genistein-treated animals where the abnormal egg clustering occurs.
(Note: This illustration was missing from
the original)
Note:
The National Toxicology Program, Center for the Evaluation of Risks to
Human Reproduction (CERHR) will hold an independent expert panel
meeting on “Genistein and Soy Formula” on March 15-17,
2006, at the Radisson Hotel Old Town, Alexandria, VA.
http://ntp.niehs.nih.gov/GenisteinSoyMtg.pdf. The NTP is an
interagency program headquartered at NIEHS.
NIEHS, a
component of the National Institutes of Health, supports research to
understand the effects of the environment on human health. For more
information on environmental health topics, please visit our website at
http://www.niehs.nih.gov/home.htm.
The
National Institutes of Health (NIH) — The Nation's Medical
Research Agency — includes 27 Institutes and Centers and is a
component of the U. S. Department of Health and Human Services. It is
the primary Federal agency for conducting and supporting basic,
clinical, and translational medical research, and it investigates the
causes, treatments, and cures for both common and rare diseases. For
more information about NIH and its programs, visit
http://www.nih.gov.
Reference:
W Jefferson, E Padilla-Banks, R Newbold and M Pepling. Neonatal
genistein treatment alters ovarian differentiation in the mouse:
Inhibition of oocyte nest breakdown and increased oocyte survival.
Biology of Reproduction, January 2006.
W
Jefferson, E Padilla-Banks and R Newbold. Adverse Effects on Female
Development and Reproduction in CD-1 Mice Following Neonatal Exposure
to the Phytoestrogen Genistein at Environmentally Relevant Doses.
Biology of Reproduction 73(4):798-806, 2005. Epub Jun 1, 2005.
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