Nonylphenol (NP), a widely diffused persistent organic pollutant (POP), has been shown to impair cerebellar development and cause cerebellum-dependent behavioral and motor deficits. The precise proliferation of granule cell precursors (GCPs), the source of granular cells (GCs), is required for normal development of cerebellum. Thus, we established an animal model of perinatal exposure to NP, investigated the effect of NP exposure on the cerebellar GCPs proliferation, and explored the potential mechanism involved. Our results showed that perinatal exposure to NP increased cerebellar weight, area, and internal granular cell layer (IGL) thickness in offspring rats. Perinatal exposure to NP also resulted in the GCPs hyperproliferation in the external granular layer (EGL) of the developing cerebellum, which may underlie the above-mentioned cerebellar alterations. However, our results suggested that perinatal exposure to NP had no effects on the length of GCPs proliferation. Meanwhile, perinatal exposure to NP also increased the activation of Notch2 signaling, the regulator of GCPs proliferation. In conclusion, our results supported the idea that exposure to NP caused the hyperproliferation of GCPs in the developing cerebellum. Furthermore, our study also provided the evidence that the activation of Notch2 signaling may be involved in the GCPs hyperproliferation.

壬基酚 (NP) 是一种广泛扩散的持久性有机污染物 (POP)，已被证明会损害小脑发育并导致依赖小脑的行为和运动缺陷。小脑的正常发育需要颗粒细胞前体 (GCP) 的精确增殖，即颗粒细胞 (GC) 的来源。因此，我们建立了围产期暴露于 NP 的动物模型，研究了 NP 暴露对小脑 GCPs 增殖的影响，并探讨了所涉及的潜在机制。我们的结果表明，围产期暴露于 NP 会增加后代大鼠的小脑重量、面积和内部颗粒细胞层 (IGL) 厚度。围产期暴露于 NP 还导致发育中小脑外部颗粒层 (EGL) 中 GCP 的过度增殖，这可能是上述小脑改变的基础。然而，我们的结果表明，围产期暴露于 NP 对 GCP 增殖的长度没有影响。同时，围产期暴露于 NP 也增加了 Notch2 信号的激活，Notch2 信号是 GCP 增殖的调节剂。总之，我们的结果支持以下观点：暴露于NP导致发育中的小脑中 GCP 的过度增殖。此外，我们的研究还提供了证据表明 Notch2 信号的激活可能与 GCP 过度增殖有关。