三丁基锡会导致成年雌性大鼠出现肥胖相关的乳腺异常。
The tributyltin leads to obesogenic mammary gland abnormalities in adult female rats.
机构信息
Dept of Morphology, Federal University of Espírito Santo, Brazil.
Laboratory of Experimental Endocrinology, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil; Postgraduate Program in Endocrinology, Faculty of Medicine and Postgraduate Program of Pharmacology and Medicinal Chemistry, Federal University of Rio de Janeiro, Brazil; Experimental Endocrinology Research, Development and Innovation Group, Institute of Biomedical Sciences, Federal University of Rio de Janeiro, Brazil.
出版信息
Toxicol Lett. 2019 Jun 1;307:59-71. doi: 10.1016/j.toxlet.2019.02.016. Epub 2019 Mar 1.
Tributyltin chloride (TBT) is an obesogen associated with several complications. However, few investigations have evaluated TBT effects on adult mammary glands (MG). In this investigation, we assessed whether TBT's obesogenic effects resulted in abnormal MG fat pad expansion and other irregularities. TBT was administered to female rats (100 ng/kg/day for 15 days via gavage), and their MG morphophysiological development was assessed. We further assessed the MG fat pad for PPARγ, ERα, and aromatase protein expression, as well as inflammation, oxidative stress (OS), apoptosis and fibrosis. Irregular MG morphological development such as lower TEB number, alveolar (AB), lobule and differentiation (DF) score were observed in TBT rats. TBT rats had abnormal MG fat accumulation as evidenced by increased numbers of hypertrophic adipocytes, triglyceride (TG) levels and PPARγ expression. A strong negative correlation between the MG obesogenic makers and TEB number, AB and DF score were observed in TBT rats. MG inflammation was observed in TBT rats. A positive correlation between the MG obesogenic markers and inflammation were observed. High ERα and aromatase expression were observed in MG of TBT rats. MG OS, apoptosis and fibrosis were present in the TBT rats. Additionally, a positive correlation between the MG obesogenic markers and OS were observed in TBT rats. Thus, these data suggest that obesogenic TBT effects led to MG irregularities in the adult female rats.
三丁基锡氯化物 (TBT) 是一种与多种并发症相关的致肥胖物。然而，很少有研究评估 TBT 对成年乳腺 (MG) 的影响。在这项研究中，我们评估了 TBT 的致肥胖作用是否导致了异常的 MG 脂肪垫扩张和其他异常。通过灌胃给雌性大鼠施用 TBT（每天 100ng/kg 持续 15 天），并评估其 MG 形态生理学发育情况。我们进一步评估了 MG 脂肪垫中过氧化物酶体增殖物激活受体 γ（PPARγ）、雌激素受体 α（ERα）和芳香酶蛋白的表达，以及炎症、氧化应激（OS）、细胞凋亡和纤维化。在 TBT 大鼠中观察到不规则的 MG 形态发育，例如 TE 数量减少、腺泡 (AB)、小叶和分化 (DF) 评分降低。TBT 大鼠的 MG 脂肪积累异常，表现为肥大脂肪细胞数量增加、三酰甘油 (TG) 水平升高和 PPARγ 表达增强。在 TBT 大鼠中，MG 致肥胖标志物与 TE 数量、AB 和 DF 评分之间存在强烈的负相关。在 TBT 大鼠中观察到 MG 炎症。MG 致肥胖标志物与炎症之间存在正相关。在 TBT 大鼠的 MG 中观察到高表达的雌激素受体 α (ERα) 和芳香酶。TBT 大鼠的 MG 存在 OS、细胞凋亡和纤维化。此外，在 TBT 大鼠中，MG 致肥胖标志物与 OS 之间存在正相关。因此，这些数据表明，致肥胖的 TBT 作用导致成年雌性大鼠的 MG 异常。
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