Banishing Glyphosate

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Banishing Glyphosate
Rising Ca 2+ concentration in the cytoplasm in turn causes Ca 2+ influx into the mitochondria and nuclei. In the mitochondria, Ca 2+
accelerates the disruption of normal oxidative metabolism leading to necrotic cell death. In nuclei, Ca 2+ modulates gene transcription
and nucleases that control apoptosis (programmed cell death that involves fragmentation of DNA).
There is already evidence that glyphosate may act as an endocrine disruptor for both males and females by altering aromatase
activity, oestrogen regulated genes, and testosterone levels in rats [10]. But Roundup acts via different mechanisms. Roundup
exposure during pregnancy and lactation at a level that did not induce maternal toxicity in Wistar rats nevertheless induced
adverse reproductive effects in male offspring, including decreased daily sperm production during adulthood, increase in abnormal
sperms, and low testosterone serum level at puberty. In exposed female offspring, only a delay in vaginal canal opening was
observed [11].
Oxidative stress and endocrine disrupting effects specific to Roundup
The key to understanding the action of Roundup on male infertility is the reactive oxygen species (ROS) generated in oxidative
stress (see [12, 13] The Body Does Burn Water and Living with Oxygen, SiS 43). Not only are ROS implicated in practically every
chronic human disease including cancer [14] (Cancer a Redox Disease, SiS 54), but also play an essential role in the pathogenesis
of many reproductive processes as detailed in a review published in 2003 [15]. In male-factor infertility, oxidative stress attacks
the lipids of the sperm plasma membrane and the integrity of DNA in the sperm nucleus. In addition, ROS induce DNA damage,
accelerate germ cell death and decrease sperm counts, thereby contributing to male infertility.
ROS is so closely linked to male infertility that infertile males generating high levels of ROS are 7 times less likely to initiate a
pregnancy compared with those with low levels of ROS. A meta-analysis demonstrated that ROS levels were significantly correlated
with the fertilization rate in couples undergoing in vitro fertilization [16].
Ashok Agarwal at the Centre for Advanced Research in Human Reproduction, Infertility and Sexual Function, Cleveland Ohio
in the United States led a retrospective study on 132 male factor infertility (MFI) patients (failure to initiate pregnancy with fertile
partner after one year of unprotected sex) consisting of 24 with all normal sperm parameters, 38 with all abnormal parameter
and the rest with 1 or more abnormal parameters [17]. They found that the 34 normal healthy donors (controls) had significantly
higher sperm concentrations, motility and morphology compared with all MFI patients. There was a significant association
between MFI and ROS with odds ratio of 4.25, independently of sperm parameters and age. They concluded that high ROS is an
independent marker of MFI, irrespective of whether these patients have normal or abnormal semen parameters. They proposed that
ROS measurement should be included a part of idiopathic infertility evaluation, and treatment with antioxidants may be beneficial
for such patents.
ROS are generated as intermediates in the central metabolic process whereby oxygen-breathing organisms obtain energy to
fuel all their activities. The energy metabolism takes place in the mitochondria, the tiny membranous powerhouses within cells
where fragments from the breakdown of glucose are oxidized ultimately into carbon dioxide and water. It involves a tightly coupled
process of oxidative phosphorylation in which electrons and protons are extracted from the chemical fragments, with electrons
transported down the electron transport chain and protons transported up the proton gradient, so that their energy can be
tapped to make ATP (adenosine triphosphate, the universal energy intermediate of the body) (for a good summary of the entire
process see Chapters 21 and 22 of [18] Living Rainbow H2O, ISIS publication). During this tightly coupled process, ROS are generated
as partially oxidized intermediates [13]. Consequently, disturbances that uncouple oxidative phosphorylation lead to a failure
of oxidation and release the partially oxidized and damaging ROS intermediates into the cell, resulting in oxidative stress.
It is very likely that the primary target of Roundup, especially its POEA surfactant, is the mitochondria, which plays a key role
in the development of sperm cells and sperm motility [19]. In addition, male infertility could arise from ROS damages to mitochondrial
DNA.
Francisco Peixoto at University of Trás-os-Montes, Real, in Portugal compared the effects of Roundup with glyphosate on
isolated rat liver mitochondria [20] and found dramatic differences. Roundup collapses the transmembrane potential of the mitochondria
and uncouples oxidative phosphorylation, depressing the rates of oxidation, with effects starting at 0.5 mM (7.5 ppm).
These effects are most likely due to non-specific permeation of the mitochondrial membrane by Roundup or its adjuvant POEA.
In addition, Roundup specifically inhibited succinate dehydrogenase, succinate cytochrome c reductase, and ATP synthase and
ATPase, key enzymes in oxidative phosphorylation. Glyphosate, on the other hand, does not have any significant effects on the
function of mitochondria up to the highest concentration used, 15 mM (253.5 ppm).
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