Department of Environmental Health Sciences, School of Public Health & Health Sciences, University of Massachusetts, Amherst, MA 01003, USA.
Biospecimen Resource and Molecular Analysis Facility, Baystate Medical Center, Springfield, MA 01199, USA.
Endocrinology. 2021 Jun 1;162(6). doi: 10.1210/endocr/bqab041.
The mammary gland is a hormone sensitive organ that is susceptible to endocrine-disrupting chemicals (EDCs) during the vulnerable periods of parous reorganization (ie, pregnancy, lactation, and involution). Pregnancy is believed to have long-term protective effects against breast cancer development; however, it is unknown if EDCs can alter this effect. We examined the long-term effects of propylparaben, a common preservative used in personal care products and foods, with estrogenic properties, on the parous mouse mammary gland. Pregnant BALB/c mice were treated with 0, 20, 100, or 10 000 µg/kg/day propylparaben throughout pregnancy and lactation. Unexposed nulliparous females were also evaluated. Five weeks post-involution, mammary glands were collected and assessed for changes in histomorphology, hormone receptor expression, immune cell number, and gene expression. For several parameters of mammary gland morphology, propylparaben reduced the effects of parity. Propylparaben also increased proliferation, but not stem cell number, and induced modest alterations to expression of ERα-mediated genes. Finally, propylparaben altered the effect of parity on the number of several immune cell types in the mammary gland. These results suggest that propylparaben, at levels relevant to human exposure, can interfere with the effects of parity on the mouse mammary gland and induce long-term alterations to mammary gland structure. Future studies should address if propylparaben exposures negate the protective effects of pregnancy on mammary cancer development.
乳腺是一种对激素敏感的器官,在有生育能力的组织重排(即怀孕、哺乳和退化)的脆弱时期易受到内分泌干扰化学物质(EDCs)的影响。人们认为怀孕对乳腺癌的发展具有长期的保护作用;然而,尚不清楚 EDC 是否会改变这种作用。我们研究了一种常见的防腐剂对生育小鼠乳腺的长期影响,这种防腐剂叫对羟基苯甲酸丙酯,具有雌激素特性,常用于个人护理产品和食品中。怀孕的 BALB/c 小鼠在整个怀孕和哺乳期接受 0、20、100 或 10000µg/kg/天的对羟基苯甲酸丙酯处理。还评估了未暴露的未生育雌性小鼠。退化后 5 周,收集乳腺并评估其组织形态学、激素受体表达、免疫细胞数量和基因表达的变化。对于乳腺形态的几个参数,对羟基苯甲酸丙酯降低了生育的效果。对羟基苯甲酸丙酯还增加了增殖,但不增加干细胞数量,并适度改变 ERα 介导基因的表达。最后,对羟基苯甲酸丙酯改变了生育对乳腺中几种免疫细胞类型数量的影响。这些结果表明,在与人类暴露相关的水平下,对羟基苯甲酸丙酯可以干扰生育对小鼠乳腺的影响,并引起乳腺结构的长期改变。未来的研究应该探讨对羟基苯甲酸丙酯暴露是否会否定怀孕对乳腺癌发展的保护作用。