Toxic Effects of Glyphosate (Roundup)

Glyphosate is a popular and broadly used herbicide that is effective against weeds, especially in association with transgenic glyphosate-resistant crop systems.  Although glyphosate is considered a low-toxic herbicide, recent studies, such as one conducted by Romano et al., have revealed toxic effects resulting from low-dose commercial formulations.  The aim of the study was to investigate the effect of gestational maternal glyphosate exposure on the reproductive development of male offspring.  Sixty-day-old male rat offspring were evaluated for sexual behavior and partner preference; serum testosterone concentrations, estradiol, follicle-stimulating hormone (FSH) and luteinizing hormone (LH); the mRNA and protein content of LH and FSH; sperm production and the morphology of the seminiferous epithelium; and the weight of the testes, epididymis and seminal vesicles.  The study found that there was an increase in sexual partner preference scores and the latency time to the first mount testosterone and estradiol serum concentrations; the mRNA expression and protein content in the pituitary gland and the serum concentration of LH; sperm production and reserves; and the height of the germinal epithelium of seminiferous tubules.  These results suggest that masculinization processes, behavior, histological processes, and endocrine processes can all be negatively impacted by maternal exposure to glyphosate.
Romano, Marco Aurelio, et al. (2013) “Glyphosate impairs male offspring reproductive development by disrupting gonadotropin expression.” Archives of toxicology 86.4: 663-673. [GSSS romano gonadotropin glyphosate]

                  Sexual differentiation in the brain takes place from late gestation to the early postnatal days.  This process is dependent on the conversion of circulating testosterone into estradiol by the enzyme aromatase.  This process will eventually determine the gener-specific reproductive endrocrinology and behavior in adults.  A reduction in aromatase activity was observed in placental and embryonic human cells treated with low concentrations of a commercial formulation of glyphosate (Benachour et al. 2007).  From previous studies, the authors suspect that the herbicide glyphosate may be characterized as a potential endocrine chemical disruptor.  Endrocrine disruptors are defined as exogenous agents that interfere with the production, release, transport, metabolism, binding, action or elimination of natural hormones responsible for the maintenance of homeostasis and the regulation of developmental processes (Kavlock et al. 1996).
                  Romano et al.investigated the effect of gestational maternal glyphosate exposure on the reproductive development of male offspring.  Sexual differentiation in the brain occurs during the late gestational and the early postnatal days. Multiple factors can influence sexual expression.  First, sexual behavior is influenced by hormones, so the serum concentrations of testosterone, estradiol, FSH and LH were measured.  The pituitary expression of mRNA and protein content of LH and FSH was also analyzed to assess the possible glyphosate-mediated interference with their production.  Sex hormone serum concentrations may also affect sperm production and the morphology of the seminiferous epithelium, which were evaluated by testicular and epididymal sperm counts and the morphometric analysis of histological sections.  Lastly, the weight of the testes, epididymides and the seminal vesicle, the growth of the animals, and the weight and age at puberty were recorded to evaluate the effect of the treatment on these conditions.
First, to verify sexual partner preferences, the males were exposed at PND60 to a sexually mature male and a female in estrous.  The males from dams treated with glyphosate spent significantly more time in contact with female rats than control animals, suggesting a preference for the female gender.  Next, the glyphosate treatment led to an increase in the latency to first mount, latency to first intromission and latency to mount after first ejaculation.  Furthermore, the levels of both testosterone and estradiol were different between the control group and the glyphosate treated group.  Specifically, the group treated with glyphosate showed higher levels of testosterone and estradiol compared to control animals.  Next, the analysis of LH mRNA expression showed increased levels in treated animals, which was accompanied by higher amounts of LH protein in the pituitary and the serum.  In addition to this, the FSH mRNA expression was increased in treated animals, but this was not associated with a rise in the FSH protein in the pituitary or the serum. 
The changes in hormones observed may influence spermatogenesis.  Thus, the researchers monitored total sperm production, daily sperm production, sperm reserves and sperm transit at PND60.  Glyphosate exposure during the perinatal period increased the total and daily sperm production.  Also, an altered morphometry of the seminiferous epithelium was observed in treated animals.  This alteration caused an increase in epithelial height and a reduction in luminal diameter without changes in the tubular diameter.  In addition, the weight of the testes was found to be similar between groups.  The weight of the undrained seminal vesicle was not altered, but the drained seminal vesicle was heavier than the control group.  This finding suggests that this structure contained a smaller amount of fluid.  Interestingly, the glyphosate rats were observed to initiate puberty at an earlier age.  This change was accompanied by a reduction in their body weight.  However, the weights of the animals at the same age were not different, indicating that observed lower weight is merely a function of the younger age at puberty onset.

This experiment indicated changes in most of the parameters evaluated.  The results suggest that maternal exposure to glyphosate disturbed the masculinization processes.  The authors conclude that glyphosate exposure promotes behavioral changes and histological and endrocrine problems.  Further study is suggested to evaluate whether the effects of maternal exposure to glyphosate are dose-dependent.

Works Cited
Benachour, Nora, et al.“Time-and dose-dependent effects of roundup on human embryonic and placental cells.” Archives of Environmental Contamination and Toxicology 53.1 (2007): 126-133.
Kavlock, Robert J., et al. “Research needs for the risk assessment of health and environmental effects of endocrine disruptors: a report of the US EPA-sponsored workshop.” Environmental health perspectives 104.Suppl 4 (1996): 715.

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