ISIS Report 27/02/12
Glyphosate Kills Rat Testis Cells
Another link between Roundup and infertility Dr. Eva
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A new study finds that Monsanto’s glyphosate-based herbicide
Roundup Bioforce® as well as glyphosate alone reduced testosterone levels in
testicular cells at very low concentrations; and at higher concentrations -
still 10 times below agricultural use – the cells died in 24-48 hours.
The study, carried out by Gilles-Éric Séralini and his colleagues at
the Université de Caen Basse-Normandie in France , was published just ahead
of reports on glyphosate contamination of groundwater in Catalonia, Spain ,
and the presence of glyphosate in urine samples of Berlin city residents at 4-20
times the level allowed in drinking water (o.1 micrograms per litre, or 0.1
parts per billion (ppb)) . American consumers exposed to glyphosate through
residual levels in genetically modified (GM) foods are likely to have even higher
levels in their system; although no studies appear to have been done.
These studies are emerging amid growing concern for the effects of
environmental contaminants on decreasing levels of male fertility in humans and
animals in industrialised nations , and there are already indications that glyphosate
herbicide is linked to infertility and other reproductive problems.
Endocrine dysfunction at very low doses
Endocrine disruption can impact a wide range of physiological
functions that includemetabolism, growth and
development, tissue function, behaviour, mood and reproduction. Healthy levels
of testosterone in men are necessary for sperm production among other things.
With previous links of pesticides to infertility, the researchers were
interested in whether glyphosate and its formulations can induce endocrine
disruption in testicular cells.
The effects of Roundup Bioforce® and glyphosate alone were tested
on three types of rat testicular cell: Leydig cells that produce testosterone,
Sertoli cells that nurture germ cells through spermatogenesis, and germ cells
that mature into sperm.
Doses of 1ppm (0.0001%) of both glyphosate and Roundup Bioforce® reduced
testosterone levels in Leydig cells by as much as 35 %, and a significant
increase in expression of aromatase was found within 24 hours. Aromatase is an
enzyme that converts testosterone to oestrogens, and its activity is important
for maintaining a healthy balance between the two hormones. These effects of
supposedly ‘non-toxic’ dilutions of the herbicide underlie glyphosate’s ability
to disrupt the endocrine system.
These results build on a long list of previous findings. Male
prepubescent rats exposed to glyphosate showed reduced testosterone levels as
well as disruption of testicular morphology and a delay in the onset of puberty
. The male offspring of rat mothers exposed to glyphosate during gestation
exhibited abnormal sexual behaviour and abnormal levels of testosterone and
estradiol, early puberty, and increased sperm count . Glyphosate exposure
reduced testosterone levels in mouse Leydig cells , and depressed aromatase
activity in human placental cell lines . The effects were more pronounced
when commercial formulations were used.
Hormonal disruption and/or reproductive problems occurred in both
humans and animals followed environmental exposure to sprayed herbicides or herbicide
residues in GM feed 
(see  Ban Glyphosate
SiS 43,  Lab Study Establishes Glyphosate Link to Birth Defects,SiS48) Regions of high glyphosate use in Argentina have seen rises in birth defects, infertility
and cancers, to the point that Argentinean doctors are calling for a complete
ban of pesticide use near residential areas and a complete ban of aerial
spraying (see  Argentina's Roundup
SiS 48  and Pesticide Illnesses
and GM Soybeans, SiS 53). Livestock consuming large amounts of GM feed have shown
increased infertility, still births, and pseudo-pregnancies, thought to be due,
at least in part, to direct endocrine-disrupting effects of glyphosate (see 
Scientist Reveals All, SiS 53).
Higher doses kill cells
and colleagues also tested whether Roundup and/or glyphosate kill testicular
cells, and whether this occurs through inducing necrosis (premature cell death
caused by external stimuli such as toxins, inflammation, infection or trauma)
or apoptosis (programmed cell death). Necrosis is first marked by a loss of
cell membrane integrity, while apoptosis is a tightly regulated process that is
marked by morphological changes such as cytoplasmic shrinkage, chromatin
condensation (the compaction and fragmentation of nuclear chromatin, with
chromatin being the native organisation of DNA wrapped around histone proteins
in the nucleus), as well as biochemical changes such as the activation of
caspase 3/7 enzymes and the release of cytochrome c from the mitochondria. In
addition, there are variations of cell death that can include necrosis-like
programmed cell death, apoptosis-like programmed cell death that lacks caspase
3/7 activation, as well as secondary necrosis where apoptotic cells eventually
also lose membrane integrity.
experiments monitored membrane integrity, caspase 3/7 activation as well as
chromatin condensation. Leydig cells showed the strongest
necrotic response, with significant membrane degradation after 1 hour of
exposure to 0.1 % Roundup. Degradation reached 5 times that of control
untreated cells at a higher concentration of 1 %, peaking at around 6 hours but
remaining significant after 48 hours.
degradation was found in cells exposed to glyphosate
alone. Thus, the effect may be due to adjuvants present in the commercial
formulation such as polyoxyethyleneamine (POEA), which is added to allow
glyphosate to penetrate plant leaves. There was no significant caspase
3/7 activation other than a small peak after 6 hours exposure. Chromatin
condensation was apparent after 24 hours
following application of 1% Roundup, as consistent with apoptosis.
Sertoli cells also showed signs of necrosis, with
membrane degradation occurring in response to 0.1% Roundup within 24 hours,
although to a lesser extent than Leydig cells. Germ cells appeared almost
insensitive, with only a slight, but statistically significant membrane
degradation following exposure to 1 % Roundup. In contrast to Leydig cells, germ
cells as well as Sertoli cell/germ cell co-cultures showed an apoptotic
response within 48 hours to 1 % glyphosate. However, there was no response to Roundup. This
disparity, as speculated by the authors may be due to distinct membrane
properties that allow glyphosate to enter germ cells more easily. This result may
also be an in vitro artefact that should be investigated further in
findings clearly show cell death responses in testicular cells, most notably in
the Leydig cells. Further experiments are needed to clarify the type of cell
death involved. As mentioned above, cell death is a complicated process.
concentration of the herbicides used in the experiments ranged from 0.0001 % (1
ppm) of Roundup Bioforce®, (corresponding to 0.366ppm of pure glyphosate) to
agricultural levels of 1 % (10,000ppm). The lowest
concentration shown to have an endocrine effect was within the range of a
previous study published by Monsanto reporting the presence of glyphosate
concentrations of up to 0.233ppm in American farmers . Further, the
permitted level of glyphosate residue on food or feed in the US is 400 ppm, or
400 times the lowest concentration tested by Seralini and colleagues. Thus, the
concentrations used in the study are very relevant to human exposure as well as
exposure of other animals. Of particular concern is the scarcity of published
data regarding the possible bioaccumulation of this herbicide, leaving us only
able to speculate how much is in our bodies.
the cell death experiments, significant results were seen with doses of 0.1%,
or 1000ppm. Although this concentration is relatively high, and well above
permitted drinking water concentrations, it is 10 times below that used in
agricultural practice, and 8 times below the maximum
level of glyphosate residue permitted in GM feed. Moreover, as shown by
the endocrine disruption experiments, cell death is not the only parameter of
acute toxicity, so while higher doses may be necessary to kill cells, low doses
can disrupt endocrine function without killing the cells, but nevertheless
impact a wide range of physiological functions, resulting in disease.
Not addressed in this study is the chronic effect
of glyphosate-based herbicide exposure; as only acute effects over 48 hours
were assessed. Chronic exposure has not been sufficiently tested, and needs to
be investigated. Furthermore, regulatory tests are usually done, not with
commercial formulations, but with glyphosate alone. As demonstrated in these and
other experiments, the adjuvants that enhance glyphosate’s action alter the
toxicity of Roundup, resulting in differing effects from those of glyphosate
linking glyphosate to birth defects and reproductive problems in both the
female and male is surely more than sufficient justification for banning this
paucity of studies assessing the presence of glyphosate and its commercial
formulations in humans also needs to be addressed.
There are 2 comments on this article so far. Add your comment
|gabriel Comment left 27th February 2012 21:09:32|
The respond of a friend.
This is so f-c-ing terrible!! Why are they not prosecuted and sentenced to the electric chair once and for all?!
|James Cooley Comment left 28th February 2012 09:09:03|
This information should grab FDA scientists and politicians by the gonads. Let them have it!