Peripubertal soy isoflavone consumption leads to subclinical hypothyroidism in male Wistar rats.

Exposure to endocrine-disrupting chemicals during critical windows of development may lead to functional abnormalities in adulthood. Isoflavones are a flavonoid group of phytoestrogens that are recognized by their estrogenic activity and are highly abundant in soybean. Since the thyroid gland presents estrogen receptors and infants, toddlers and teenagers may consume isoflavones from soy-based infant formula and beverages as alternatives to animal milk, we propose to investigate the potential effects of relevant concentrations of soy isoflavones in the regulation of the hypothalamic-pituitary (HP) thyroid axis using peripubertal male rats as an experimental model. Thirty-two 23-day-old male rats were exposed to 0.5, 5, or 50 mg of soy isoflavones/kg from weaning to 60 days of age, when they were euthanized, and the tissues were collected to evaluate the mRNA expression of genes involved in the regulation of the HP thyroid axis and dosages of thyroid hormones (THs). Serum TSH concentrations were increased, while alterations were not observed in serum concentrations of triiodothyronine and thyroxine. Regarding mRNA gene expression, Mct-8 was increased in the hypothalamus, Mct-8, Thra1, and Thrb2 were decreased in the pituitary, and Nis and Pds were reduced in the thyroid. In the heart, Mct8 and Thrb2 were increased, and Thra1 was decreased. In the liver, Mct8, Thra1, and Thrb2 were decreased. These results suggest that the consumption of relevant doses of soy isoflavones during the peripubertal period in males may induce subclinical hypothyroidism, with alterations in the regulation of the HP thyroid axis, modulation of TH synthesis, and peripheral alterations in TH target organs.

Consumption of soy isoflavones during the prepubertal phase delays puberty and causes hypergonadotropic hypogonadism with disruption of hypothalamic-pituitary gonadotropins regulation in male rats.

Isoflavones are phytoestrogens with recognized estrogenic activity but may also affect testosterone, corticosterone and thyroid hormone levels in experimental models. However, the molecular mechanisms involved in these alterations are still unclear. Isoflavones are present in soy-based infant formula, in breast milk after the consumption of soy by the mother and are widely used for the preparation of beverages consumed by toddlers and teenagers. In this sense, we proposed to investigate the effects of soy isoflavone exposure during the prepubertal period, a recognized window of sensitivity for endocrine disruption, over the hypothalamic-pituitary-testicular (HPT) axis. For this, 42 3-week-old male Wistar rats were exposed to 0.5, 5 or 50 mg of soy isoflavones/kg from postnatal day (PND) 23 to PND60. We evaluated body growth, age at puberty, serum concentrations of LH, FSH, testosterone and estradiol, and the expression of the transcripts (mRNA) of genes encoding key genes controlling the hypothalamic-pituitary-testicular (HPT) axis. In the hypothalamus, we observed an increase in Esr1 mRNA expression (0.5 and 5 mg). In the pituitary, we observed an increase in Gnrhr mRNA expression (50 mg), a reduction in Lhb mRNA expression (0.5 mg), and a reduction in Ar mRNA expression. In the testis, we observed an increase in Lhcgr mRNA expression (50 mg) and a reduction in Star mRNA expression (0.5 and 5 mg). The serum levels of LH (5 and 50 mg) and FSH (0.5 mg) were increased, while testosterone and estradiol were reduced. Puberty was delayed in all groups. Taken together, these results suggest that prepubertal consumption of relevant levels of soy isoflavones disrupts the HPT axis, causing hypergonadotropic hypogonadism and altered expression levels of key genes regulating the axis.

Intraperitoneal exposure to nano/microparticles of fullerene (C60) increases acetylcholinesterase activity and lipid peroxidation in adult zebrafish (Danio rerio) brain.

Even though technologies involving nano/microparticles have great potential, it is crucial to determine possible toxicity of these technological products before extensive use. Fullerenes C60 are nanomaterials with unique physicochemical and biological properties that are important for the development of many technological applications. The aim of this study was to evaluate the consequences of nonphotoexcited fullerene C60 exposure in brain acetylcholinesterase expression and activity, antioxidant responses, and oxidative damage using adult zebrafish as an animal model. None of the doses tested (7.5, 15, and 30 mg/kg) altered AChE activity, antioxidant responses, and oxidative damage when zebrafish were exposed to nonphotoexcited C60 nano/microparticles during 6 and 12 hours. However, adult zebrafish exposed to the 30 mg/kg dose for 24 hours have shown enhanced AChE activity and augmented lipid peroxidation (TBARS assays) in brain. In addition, the up-regulation of brain AChE activity was neither related to the transcriptional control (RT-qPCR analysis) nor to the direct action of nonphotoexcited C60 nano/microparticles on the protein (in vitro results) but probably involved a posttranscriptional or posttranslational modulation of this enzymatic activity. Taken together these findings provided further evidence of toxic effects on brain after C60 exposure.