Skip to main content

News & Media

News & Media Front Page

Chemicals Used to Protect Soldiers in 1991 Gulf War Can Damage Testes, Animal Studies Show

Contact

Duke Health News 919-660-1306

DURHAM, N.C. -- A combination of chemicals given to protect
Gulf War soldiers against deadly diseases and nerve gas may
have inadvertently damaged their testes and sperm production,
according to animal experiments at Duke University Medical
Center.

The new study could explain why some veterans have
experienced infertility, sexual dysfunction, and other
genitourinary symptoms, said Mohamed Abou Donia, Ph.D., a Duke
pharmacologist.

Three chemicals were given to soldiers to protect them
against insect-borne diseases and nerve-gas poisoning: the
insect repellent DEET, the insecticide permethrin, and the
anti-nerve gas agent pyridostigmine bromide.

In a study designed to mimic those same conditions, Abou
Donia and his colleagues gave rats equivalent doses to what the
soldiers received. When given together, the chemicals caused
extensive cell degeneration and cell death with various
structures of the testes, he found. The damage was even more
severe among rats that were exposed to moderately stressful
situations in addition to the chemicals.

Results of the study, funded by the Department of Defense,
are published in the Jan. 10, 2003 issue of The Journal of
Toxicology and Environmental Health.

"It appears that moderate stress, combined with the three
chemicals, caused the most severe deterioration in testicular
structure and sperm production, and these conditions were
likely experienced by some Gulf War soldiers in the combat
environment," said Abou Donia, principal investigator of the
study.

"Interestingly, the chemically-treated rats don't look or
behave any differently than normal rats, just as the soldiers
don't show any outward signs of disease," said Abou Donia. "But
under a microscope, you can see clear and well-defined damage
to a variety of testicular structures."

Abou Donia's team found the most pervasive cell damage
within basal germ cells and spermatocytes, which give rise to
mature sperm. The three chemicals combined with stress caused
these cells to detach from one another, slough off, and develop
holes known as "vacuoles." Such changes are well-known stages
in the progression toward programmed cell death, known as
apoptosis. The more cells that die, the greater the suppression
of "spermatogenesis" or sperm production, said Abou Donia.

In fact, pathologic exams showed that most of the developing
stages of sperm were interrupted, and some of the stages were
absent altogether among rats treated with all three chemicals
and stressful conditions.

Similar cell degeneration occurred in the seminiferous
tubules, where developing sperm are produced, and Sertoli cells
that support and nurture the developing germ cells.

"On every objective measure, the testes showed severe
degeneration in the presence of multiple chemicals, suggesting
that the chemicals have a synergistic or additive effect," said
Abou Donia.

BRAIN DEFICITS COINCIDE WITH REPRODUCTIVE DAMAGE

The testicular damage corresponds to equally devastating
brain changes in the same rats exposed to the chemicals plus
stress, said Abou Donia. Findings from those experiments were
published in the August 2002, issue of Neurobiology of
Disease.

In that study, Abou Donia's team showed that chemicals and
stress increased the permeability of the blood-brain barrier,
allowing substances that would normally be blocked to enter the
brain. Moreover, the researchers found large numbers of dead
neurons, or nerve cells, in regions of the brain that control
muscle strength and movement (cortex); balance and coordination
(cerebellum); and memory, cognition and mood (hippocampus). Yet
the animals appeared normal to the naked eye.

Similarly, Gulf War veterans have complained of deficits in
these very functions for more than a decade, while clinical
exams show no obvious signs of disease.

"The brain deficits we found in rats reside in specific
areas of the brain that we can't measure in living humans,"
said Abou Donia. "This is why the deficits are so difficult to
assess clinically and why animal studies are so critical to
understanding the cellular damage."

Complicating the diagnostic process even further is the
sheer volume of brain cells that must die before clinical
deficits become obvious, he said. The human brain contains
billions of nerve cells and supporting cells, so the loss of
brain cells does not produce immediate and overt symptoms.
Often, it takes repeated exposures to chemicals before the
brain is depleted of enough neurons to trigger deficits, he
said.

However, once the damage occurs, little can be done to
repair it. Extensive nerve cell death causes "holes" in the
brain and thus permanent deficits, because neurons cannot
regenerate like other cells in the body.

"Many of the effects we see with chemical exposure are
similar to those of aging, which is also associated with fewer
neurons," said Abou Donia. He said his ongoing research should
help prevent such debilitating conditions in the future.

"The military used these chemicals with the best of
intentions, to protect soldiers from indigenous diseases in the
Gulf War region," he said. "Without protection, there may have
been thousands of deaths. But it appears that the precautions
prevented one set of problems while creating another. Now, our
task is to discern the mechanisms of illness in order to
provide the soldiers with maximum protection and the least risk
of chemically induced injury."

Duke colleagues Hagir B. Suliman, Ph.D., Wasiuddin A. Khan,
Ph.D., and Ali A. Abdel-Rahman were co-authors of the
paper.

News & Media Front Page