Thyroid redox imbalance in adult Wistar rats that were exposed to nicotine during breastfeeding

Abstract

Maternal nicotine exposure causes several consequences in offspring phenotype, such as obesity and thyroid dysfunctions. Nicotine exposure can increase oxidative stress levels, which could lead to thyroid dysfunction. However, the mechanism by which nicotine exposure during breastfeeding leads to thyroid gland dysfunction remains elusive. We aimed to investigate the long-term effects of maternal nicotine exposure on redox homeostasis in thyroid gland, besides other essential steps for thyroid hormone synthesis in rats from both sexes. Lactating Wistar rats were implanted with osmotic minipumps releasing nicotine (NIC, 6 mg/kg/day) or saline (control) from postnatal day 2 to 16. Offspring were analyzed at 180-day-old. NIC males showed lower plasma TSH, T3 and T4 while NIC females had higher T3 and T4. In thyroid, NIC males had higher sodium-iodide symporter protein expression, whereas NIC females had higher thyroid-stimulating hormone receptor (TSHr) and thyroperoxidase (TPO) protein expression. TPO activity was lower in NIC males. Hydrogen peroxide generation was decreased in NIC males. Activities of superoxide dismutase, catalase and glutathione peroxidase were compromised in NIC animals from both sexes. 4-Hydroxynonenal was higher only in NIC females, while thiol was not affected in NIC animals from both sexes. NIC offspring also had altered expression of sex steroid receptors in thyroid gland. Both sexes showed similar thyroid morphology, with lower follicle and colloid size. Thyroid from female offspring exposed to nicotine during breastfeeding developed oxidative stress, while the male gland seemed to be protected from redox damage. Thyroid dysfunctions seem to be associated with redox imbalance in a sex-dependent manner.

Nicotine exposure during breastfeeding alters the expression of endocannabinoid system biomarkers in female but not in male offspring at adulthood

“…This finding agrees with findings of our previous studies. [11][12][13] ECS markers in the lateral hypothalamus (LH) and paraventricular nucleus (PVN)…”

“…10 We have previously demonstrated that maternal nicotine exposure during lactation compromises rat offspring's phenotype at long-term in a sex-dependent manner: male offspring showed, at adulthood, obesity, normophagia, despite hypothalamic leptin resistance, hyperleptinemia, hypercorticosteronemia and hypothyroidism, while female offspring had normal body mass, despite hyperphagia, unchanged leptinemia and corticosteronemia, but hyperthyroidism. [11][12][13] Several different mechanisms have been associated with endocrine dysfunctions, some of which have been linked to obesity onset. Studies have already described an interaction of a disturbed endocannabinoid system (ECS) with endocrine system changes and obesity.…”

Relationship between dietary selenium intake and serum thyroid function measures in U.S. adults: Data from NHANES 2007–2012

“…Previous studies have demonstrated that estrogens could increase iodine uptake, thyroperoxidase activity, thyroglobulin expression, and modulate TSH levels ( 36 – 38 ). Moreover, estrogens also influence thyroid gland redox status by regulating nicotinamide adenine dinucleotide phosphate oxidase 4 (NOX4) and dual oxidase 2 (DUOX2) activity and expression ( 37 ). Selenium might have a much weaker effect on thyroid hormones than estrogens, suggesting that the effect of dietary selenium intake on thyroid hormones may be more significant in male adults.…”

Neonatal nicotine exposure changes insulin status in fat depots: sex-related differences

“…75 Recently, our group demonstrated that male nicotine offspring have lower testosterone levels while the female offspring have no difference in plasma levels of testosterone and estradiol. 76 Males with hypogonadism have reduced androgen and increased adiposity. Epidemiological studies show a positive correlation between hypogonadism and obesity, such as type 2 diabetes mellitus and metabolic syndrome.…”