3. Hormonal effects: Both NK603 maize and Roundup significantly and independently disrupted hormonal regulation. Substances that do this are known as endocrine disruptors. Published evidence was cited to suggest possible avenues through which this might happen.
The GM trait inserted into NK603 intentionally over-expresses a key enzyme which would otherwise be suppressed by glyphosate. The GM version of the enzyme is unaffected by glyphosate, meaning that the GM plant can survive despite being sprayed with glyphosate herbicide.
However, in its original, unmodified state, this enzyme catalyzes the first step in the shikimic acid pathway, a major metabolic trunk with many outcomes. One of those outcomes is the production of the metabolites, caffeic and ferulic acids, which may inhibit the growth of tumours. Ferulic acid is also known to modulate estrogenic activity in mammals. Most mammary tumours are known to be estrogen-responsive. The reduced levels of caffeic and ferulic acid found in GM NK603 maize in this study would be consistent with the observed trends in tumour occurrence, and specifically, with increased incidence of mammary tumours.
In addition to possible downstream metabolic impacts from the GM trait, it is also necessary to account for the independent effect of glyphosate. Roundup, which may be present as a residue in the sprayed GM maize treatments as well as in the dosed water treatments, is known to disrupt aromatase. This pivotal enzyme, also known as estrogen synthetase, catalyzes the conversion of androgen to estrogen. Roundup has further been shown to impact upon androgen and estrogen receptors, and to act as an endocrine disruptor of sex hormones (see evidence cited in the Séralini study). Furthermore, glyphosate has been shown to act as an estrogen substitute capable of stimulating the growth of estrogen-dependent breast cancer cells at very low doses. This may be a contributing factor to the more rapid growth of mammary tumours in at least the Roundup treatment groups.
Thus both the GM maize and the Roundup herbicide it relies upon had toxic effects on the mammalian physiology in a gender-specific way. In other words, the effects on males were different from the effects on females.
Treatment responses recorded in this study were nonlinear, meaning that the effect did not increase in proportion to the dose. They appeared to be more reflective of a threshold-type response. For example, incidence of NRPT in female rats was uniform across all three doses of Roundup in drinking water. This would suggest that even the lowest dose was high enough to meet the threshold for a full response. Endocrine disruptor effects can act at extremely low concentrations and can be nonlinear. This may explain why in the present study, mortality appeared to be higher in male rats fed a diet containing 11% GM maize than a diet containing 22% or 33% GM maize.
The findings of the study challenge the central premise of GM, namely that it is feasible to insert a transgene to confer a single specific trait without compromising the expression of other apparently unrelated traits.
 Thongprakaisang S et al. (2013). Glyphosate induces human breast cancer cells growth via estrogen receptors. Food Chem Toxicol.
 Vandenberg LN et al. (2012). Hormones and endocrine-disrupting chemicals: Low-dose effects and nonmonotonic dose responses. Endocr Rev 33(3): 378-455.