Subacute tributyltin exposure alters the development and morphology of mammary glands in association with CYP19A1 expression in female rats

IF 3.3 4区医学 Q2 REPRODUCTIVE BIOLOGY Reproductive toxicology Pub Date : 2024-06-26 DOI:10.1016/j.reprotox.2024.108635

Natalia P. Silva , Charles S. da Costa , Kayke L. Barbosa , Cidália de F. Januario , Leticia N. Gama-de-Souza , Cinthia Breves , Rodrigo S. Fortunato , Leandro Miranda-Alves , Miriane de Oliveira , Celia R. Nogueira , Jones B. Graceli

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Abstract

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.

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亚急性三丁基锡暴露会改变雌性大鼠乳腺的发育和形态，这与 CYP19A1 的表达有关。

三丁基锡（TBT）是一种与生殖功能障碍有关的干扰内分泌的化学物质（EDC）。然而，很少有研究调查了接触三丁基锡化合物对乳腺发育的影响。因此，我们评估了亚急性三丁基锡化合物暴露是否会导致乳腺发育异常。我们给出生后第 25 天至第 55 天的雌性大鼠注射了三丁基锡化合物（100 和 1,000 纳克/千克/天，共 30 天），并对乳腺发育、形态、炎症、胶原沉积和蛋白质表达进行了评估。在两个三丁基锡化合物组中都观察到乳腺发育异常。具体来说，暴露于三丁基锡化合物会减少末端芽（TEB）、1 型肺泡芽（AB1）和 2 型肺泡芽（AB2）的数量。在三丁基锡化合物大鼠的乳腺中发现，小叶和分化（DF）2 评分增加。接触三丁基锡化合物会增加乳腺血管、肥大细胞数量和胶原沉积。此外，两种 TBT 大鼠都表现出导管内增生和 TEB 样结构。在三丁基锡化合物大鼠的乳腺中观察到雌激素受体α（ERα）、孕酮受体（PR）和细胞色素 P450 家族 19 亚家族 A 成员 1（CYP19A1）阳性细胞的增加。在 CYP19A1 阳性细胞和 TEB 数量之间观察到强烈的负相关。此外，CYP19A1 阳性细胞与乳腺 TEB 样结构、导管增生、炎症和胶原沉积呈正相关。因此，这些数据表明，接触三丁基锡化合物会通过调节雌性大鼠的 CYP19A1 信号通路损害乳腺发育。

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来源期刊

Reproductive toxicology 生物-毒理学

CiteScore

6.50

自引率

3.00%

发文量

131

审稿时长

45 days

期刊介绍： Drawing from a large number of disciplines, Reproductive Toxicology publishes timely, original research on the influence of chemical and physical agents on reproduction. Written by and for obstetricians, pediatricians, embryologists, teratologists, geneticists, toxicologists, andrologists, and others interested in detecting potential reproductive hazards, the journal is a forum for communication among researchers and practitioners. Articles focus on the application of in vitro, animal and clinical research to the practice of clinical medicine. All aspects of reproduction are within the scope of Reproductive Toxicology, including the formation and maturation of male and female gametes, sexual function, the events surrounding the fusion of gametes and the development of the fertilized ovum, nourishment and transport of the conceptus within the genital tract, implantation, embryogenesis, intrauterine growth, placentation and placental function, parturition, lactation and neonatal survival. Adverse reproductive effects in males will be considered as significant as adverse effects occurring in females. To provide a balanced presentation of approaches, equal emphasis will be given to clinical and animal or in vitro work. Typical end points that will be studied by contributors include infertility, sexual dysfunction, spontaneous abortion, malformations, abnormal histogenesis, stillbirth, intrauterine growth retardation, prematurity, behavioral abnormalities, and perinatal mortality.