三丁基锡(TBT)是与生殖功能障碍有关的内分泌干扰化学物质(EDC)。然而,很少有研究研究TBT暴露对乳腺发育的影响。因此,我们评估了亚急性TBT暴露是否会导致乳腺发育异常.我们从出生后(PND)25天到PND55天对雌性大鼠施用TBT(100和1,000ng/kg/天,持续30天),乳腺发育,形态学,炎症,胶原蛋白沉积,和蛋白质表达进行评估。在两个TBT组中观察到异常的乳腺发育。具体来说,TBT暴露减少了末端芽(TEB)的数量,1型(AB1)肺泡芽,和2型(AB2)肺泡芽。在TBT大鼠的乳腺中发现小叶和分化(DF)2评分增加。TBT暴露会增加乳腺血管,肥大细胞数,和胶原蛋白沉积。此外,两只TBT大鼠均表现为导管内增生和TEB样结构。雌激素受体α(ERα)的增加,孕激素受体(PR),在TBT大鼠的乳腺中观察到细胞色素P450家族19亚家族A成员1(CYP19A1)-阳性细胞。CYP19A1-阳性细胞数与TEB数呈显著负相关。此外,CYP19A1-阳性细胞与乳腺TEB样结构呈正相关,导管增生,炎症,和胶原蛋白沉积。因此,这些数据表明TBT暴露通过调节CYP19A1信号通路损害雌性大鼠的乳腺发育。
Tributyltin (TBT) is an endocrine-disrupting chemical (EDC) related to reproductive dysfunctions. However, few studies have investigated the effects of TBT exposure on mammary gland development. Thus, we assessed whether subacute TBT exposure causes irregularities in mammary gland development. We administered TBT (100 and 1,000 ng/kg/day for 30 days) to female rats from postnatal day (PND) 25 to PND 55, and mammary gland development, morphology, inflammation, collagen deposition, and protein expression were evaluated. Abnormal mammary gland development was observed in both TBT groups. Specifically, TBT exposure reduced the number of terminal end buds (TEBs), type 1 (AB1) alveolar buds, and type 2 (AB2) alveolar buds. An increase in the lobule and differentiation (DF) 2 score was found in the mammary glands of TBT rats. TBT exposure increased mammary gland blood vessels, mast cell numbers, and collagen deposition. Additionally, both TBT rats exhibited intraductal hyperplasia and TEB-like structures. An increase in estrogen receptor alpha (ERα), progesterone receptor (PR), and cytochrome P450 family 19 subfamily A member 1 (CYP19A1) - positive cells was observed in the mammary glands of TBT rats. A strong negative correlation was observed between CYP19A1- positive cells and TEB number. In addition, CYP19A1 - positive cells were positively correlated with mammary gland TEB-like structure, ductal hyperplasia, inflammation, and collagen deposition. Thus, these data suggest that TBT exposure impairs mammary gland development through the modulation of CYP19A1 signaling pathways in female rats.