Environmental obesogen tributyltin chloride leads to abnormal hypothalamic-pituitary-gonadal axis function by disruption in kisspeptin/leptin signaling in female rats

Sena, Gabriela C.; Freitas-Lima, Leandro Ceotto; Merlo, Eduardo; Podratz, Priscila L.; Araújo, Julia F.P. de; Brandão, Poliane A.A.; Carneiro, Maria Tereza Weitzel Dias; Zicker, Marina Campos; Ferreira, Adaliene Versiani Matos; Takiya, Christina Maeda; Barbosa, Carolina Monteiro de Lemos; Morales, Marcelo M.; Santos-Silva, Ana Paula; Miranda-Alves, Leandro; Silva, Ian V.; Graceli, Jones Bernardes

doi:10.1016/j.taap.2017.01.021

Cited by 76 publications

(47 citation statements)

References 96 publications

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“…Consistent with previous studies, a significant increase in the body weight of mice was observed in the 50 μg·kg −1 TBTCl group in the present study. Moreover, several papers showed that TBTCl resulted in increased epididymal adipose mass in mice, as shown in this study.…”

Section: Discussionsupporting

confidence: 93%

Tributyltin reduces the levels of serum adiponectin and activity of AKT and induces metabolic syndrome in male mice

Yan

Guo

Cheng

et al. 2018

Environmental Toxicology

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Tributyltin (TBT), a proven environmental obesogen, functions as a nanomolar agonist of the peroxisome proliferator activated receptor-γ (PPARγ). However, the adverse effects of TBT on metabolism are incompletely understood. In this study, male ICR mice were administered TBT (5 and 50 μg·kg ) by an intraperitoneal injection once every 3 days for 30 days from 28 days of age and bred for another 30 days after the last administration of TBT. We analyzed the effects of these exposures on the fat depot weights, serum lipid profile, serum leptin and adiponectin, hepatic lipid accumulation, and activity of AKT in the liver and skeletal muscle isolated from mice 8 mins after receiving an insulin injection. Pubertal exposure to TBTCl resulted in a higher body weight, increased epididymal and liver fat accumulation, hyperlipidemia, an elevated low-density lipoprotein/high-density lipoprotein ratio, serum adiponectin deficiency, worse glucose tolerance, and lower insulin-dependent AKT phosphorylation in the liver and muscle in mice. These results showed that TBT exposure induced peripheral insulin resistance and metabolic syndrome in mice.

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Section: Discussionsupporting

confidence: 93%

Tributyltin reduces the levels of serum adiponectin and activity of AKT and induces metabolic syndrome in male mice

Yan

Guo

Cheng

et al. 2018

Environmental Toxicology

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“…Grote et al ( 29 ) demonstrated that rats treated with 6 mg/kg of TPTCl had increased serum estrogen levels. By contrast, other studies have shown a reduction in the serum estrogen levels and increased testosterone in TBTCl-treated rats ( 14 , 27 , 31 , 36 ). Ma et al ( 24 ) demonstrated that azocyclotin treatment caused an increase in testosterone levels and a decrease in estrogen levels in the ovaries of female zebra fish.…”

Section: Reproductive Toxicologycontrasting

confidence: 59%

“…Organotins can also affect the female reproductive function in different animal models ( 12 , 16 , 19 , 28 – 30 ). Rats exposed to 100 ng/kg of TBTCl have abnormalities in the estrous cycle and present increased ovary and serum tin levels ( 14 , 31 ). In addition, OTs led to a decrease in the weight of the reproductive organs of rodents in a dose-dependent manner ( 21 , 32 – 35 ).…”

Section: Reproductive Toxicologymentioning

confidence: 99%

“…Furthermore, it has been reported that exposure to OTs causes impairment of the release and production of sex hormones ( 14 , 24 , 27 , 29 , 33 ). Grote et al ( 29 ) demonstrated that rats treated with 6 mg/kg of TPTCl had increased serum estrogen levels.…”

Section: Reproductive Toxicologymentioning

confidence: 99%

“…For humans and other vertebrates, the major route of OTs exposure is by the intake of contaminated seafood, and studies evaluating their toxicological risks are limited ( 7 – 11 ). OTs impair reproductive functioning, and the damage is associated with the imbalance of sex hormones and with improper modulation of the hypothalamic–pituitary–gonadal axis function of rodents ( 12 – 14 ). Here, we report that OTs act as reproductive disruptors in vertebrate studies (Table 1 ); among them are tetrabutyltin (TeBT), tributyltin chloride (TBTCl), tributyltin acetate (TBTAc), triphenyltin chloride (TPTCl), triphenyltin hydroxide (TPTOH), dibutyltin chloride (DBTCl), dibutyltin dichloride (DBTCl2), diphenyltin dichloride (DPTCl2), monobutyltin (MBT), and azocyclotin.…”

Section: Introductionmentioning

confidence: 99%

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Organotin Exposure and Vertebrate Reproduction: A Review

et al. 2018

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Organotin (OTs) compounds are organometallic compounds that are widely used in industry, such as in the manufacture of plastics, pesticides, paints, and others. OTs are released into the environment by anthropogenic actions, leading to contact with aquatic and terrestrial organisms that occur in animal feeding. Although OTs are degraded environmentally, reports have shown the effects of this contamination over the years because it can affect organisms of different trophic levels. OTs act as endocrine-disrupting chemicals (EDCs), which can lead to several abnormalities in organisms. In male animals, OTs decrease the weights of the testis and epididymis and reduce the spermatid count, among other dysfunctions. In female animals, OTs alter the weights of the ovaries and uteri and induce damage to the ovaries. In addition, OTs prevent fetal implantation and reduce mammalian pregnancy rates. OTs cross the placental barrier and accumulate in the placental and fetal tissues. Exposure to OTs in utero leads to the accumulation of lipid droplets in the Sertoli cells and gonocytes of male offspring in addition to inducing early puberty in females. In both genders, this damage is associated with the imbalance of sex hormones and the modulation of the hypothalamic–pituitary–gonadal axis. Here, we report that OTs act as reproductive disruptors in vertebrate studies; among the compounds are tetrabutyltin, tributyltin chloride, tributyltin acetate, triphenyltin chloride, triphenyltin hydroxide, dibutyltin chloride, dibutyltin dichloride, diphenyltin dichloride, monobutyltin, and azocyclotin.

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