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."
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