The tributyltin leads to obesogenic mammary gland abnormalities in adult female rats

• Published in: Toxicology letters 2019-06, Vol.307, p.59-71
• Main Authors: da Costa, Charles S., Miranda-Alves, Leandro, La Merrill, Michele A., Silva, Ian V., Graceli, Jones B.
• Format: Article
• Language: English
• Subjects: Adipocytes - drug effects; Adipocytes - pathology; Adipose Tissue - drug effects; Adipose Tissue - pathology; Animals; Breast Diseases - chemically induced; Breast Diseases - pathology; Endocrine-disrupting chemicals; ERα/aromatase; Estrous Cycle - drug effects; Female; Inflammation; Mammary gland fat pad; Mammary Glands, Animal - drug effects; Mammary Glands, Animal - pathology; Oxidative stress; Oxidative Stress - drug effects; PPAR gamma - metabolism; Rats; Rats, Wistar; Trialkyltin Compounds - toxicity; Tributyltin chloride; Triglycerides - metabolism
• ISSN: 0378-4274; 1879-3169
• DOI: 10.1016/j.toxlet.2019.02.016

[Display omitted] •TBT disrupted the normal morphology of the mammary gland in adult female rats.•TBT leads to abnormal mammary gland fat accumulation by PPARγ expression.•Abnormal mammary gland fat accumulation by TBT may be associated with other mammary gland irregularities. 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.