Despite numerous studies on the environmental health and safety (EHS) of silver nanoparticles (AgNPs), most studies looked into their gross toxicities with rather limited understanding on their labyrinthine implicit effects on the target sites, such as the endocrine system. Burgeoning evidence documents the disrupting effects of AgNPs on endocrine functions; however, little research has been invested to recognize the potential impacts on the mammary gland, a susceptible estrogen-responsive organ. Under this setting, we here aimed to scrutinize AgNP-induced effects on the development of pubertal mammary glands at various concentrations that bear significant EHS relevance. We unearthed that AgNPs could accumulate in mouse mammary glands and result in a decrease in the percentage of ducts and terminal ducts in the adult mice after chronic exposure. Strikingly, smaller sized AgNPs showed greater capability to alter the pubertal mammary development than larger sized particles. Intriguingly, mechanistic investigation revealed that the reduction of epithelial proliferation in response to AgNPs was ascribed to reduced ERα expression, which, at least partially, accounted for diseased epithelial morphology in mammary glands. Meanwhile, the decline in fibrous collagen deposition around the epithelium was found to contribute to the compromised development of mammary glands under the exposure of AgNPs. Moreover, as an extension of the mechanism, AgNPs diminished serum levels of estradiol in exposed animals. Together, these results uncovered a novel toxicity feature of AgNPs: compromised development of mouse pubertal mammary glands through the endocrine-disrupting actions. This study would open a new avenue to unveil the EHS impacts of AgNPs.

尽管对银纳米颗粒（AgNPs）的环境健康和安全性（EHS）进行了大量研究，但大多数研究仍在对其迷宫素对靶位（例如内分泌系统）的隐性影响了解甚少的情况下，对其总毒性进行了研究。新兴证据证明了AgNP对内分泌功能的破坏作用。然而，很少有研究可以识别对乳腺的潜在影响，乳腺是一种易感的雌激素反应器官。在此背景下，我们的目标是仔细研究AgNP诱导的各种浓度的EHS相关性对青春期乳腺发育的影响。我们发现，AgNPs可能会在小鼠乳腺中积聚，并导致成年小鼠长期暴露后导管和末端导管的百分比降低。令人惊讶的是，与较大尺寸的颗粒相比，较小尺寸的AgNPs具有更大的改变青春期乳房发育的能力。有趣的是，机理研究表明，响应于AgNPs的上皮增殖减少归因于ERα表达降低，这至少部分地解释了乳腺中病变的上皮形态。同时，发现在上皮周围的纤维胶原蛋白沉积的减少导致在暴露于AgNPs的情况下乳腺的发育受到损害。此外，作为该机制的扩展，AgNPs减少了暴露动物的血清雌二醇水平。在一起，这些结果揭示了AgNPs的新的毒性特征：通过破坏内分泌的作用而损害了小鼠青春期乳腺的发育。