Silver nanoparticles (AgNPs) are widely used in industrial and medical applications and humans may be exposed through different routes, increasing the risk of toxicity. We investigated the transcript expression of genes involved in the regulation of the hypothalamic-pituitary-testicular (HPT) axis and the parameters associated with sperm functionality after prepubertal exposure. AgNPs modulated the transcript expression of genes involved in the control of the HPT axis and spermatogenesis in the groups treated with lower doses, while the functional parameters related to sperm and puberty were affected in the groups administered higher doses. These results suggest that the HPT axis is disrupted by AgNPs during the prepubertal and pubertal periods, which are highly susceptible windows for the endocrine-disrupting chemical activity.
Humans and environments are constantly
exposed to a wide range
of commercial products containing silver nanoparticles (AgNPs) in
their composition. The hypothalamic-pituitary-testicular (HP-testicular)
axis is sensitive to low doses of AgNPs with repercussions in sperm
functionality. The oxidative stress may be related to the pathogenesis
of sperm alterations because Ag+ ions are released from
AgNPs in the corporal fluids. This study aimed to investigate the
effects of AgNP exposure in the antioxidant defense system. For this,
the transcript expression and the activity of catalase (CAT), superoxide
dismutase (SOD), glutathione peroxidase (GPX), and glutathione reductase
(GSR) enzymes were evaluated in the testis of rats exposed during
the prepubertal period to increasing doses of AgNPs (1.875, 3.75,
7.5, or 15 μg of AgNPs/kg). The higher dose of AgNPs (15 μg/kg)
investigated promoted increases in the activity of CAT, GPX, and GSR
enzymes and in the expression of Gpx4 var1 transcript.
The exposure to 7.5 μg/kg of AgNP increased the Gpx4
var1 mRNA expression. In the group that received 3.75 μg
of AgNP/kg, the expression of Sod1, Gpx4 var2, and Gsr transcripts was decreased while the Gpx4 var1 mRNA expression was augmented. The lower dose of AgNPs tested (1.875
μg/kg) increased the expression of Cat and Gpx4 var1 transcripts. Thus, AgNP alters the expression
and activity of the antioxidant enzymes in a nonmonotonic dose–response
curve and directly or indirectly modulates the events related to spermatogenesis
process.
The increased incidence of thyroid diseases raises a series of questions about what the main predisposing factors are nowadays. If dietary restriction of iodine was once a major global health concern, today, the processes of industrialization of food and high exposure to a wide variety of environmental chemicals may be affecting, directly or indirectly, thyroid function. The homeostasis of hypothalamus–pituitary–thyroid (HPT) axis is finely regulated through the negative feedback mechanism exerted by thyroid hormones. Allostatic mechanisms are triggered to adjust the physiology of HPT axis in chronic conditions. Glyphosate and glyphosate-based herbicides are pesticides with controversial endocrine disrupting activities and only few studies have approached their effects on HPT axis and thyroid function. However, glyphosate has an electrophilic and nucleophilic zwitterion chemical structure that may affect the mechanisms involved in iodide oxidation and organification, as well as the oxidative phosphorylation in the ATP synthesis. Thus, in this review, we aimed to: (1) discuss the critical points in the regulation of HPT axis and thyroid hormones levels balance, which may be susceptible to the toxic action of glyphosate and glyphosate-based herbicides, correlating the molecular mechanisms involved in glyphosate toxicity described in the literature that may, directly or indirectly, be associated to the higher incidence of thyroid diseases; and (2) present the literature regarding glyphosate toxicity in HPT axis.
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