Sympathetic nerves innervate most organs and regulate organ blood flow. Specifically, in the uterus, estradiol (E2) elicits rapid degeneration of sympathetic axons and stimulates the growth of blood vessels. Both physiological remodeling processes, critical for reproduction, have been extensively studied but as independent events and are still not fully understood. Here, we examine the neuropilin-1 (NRP1), a shared receptor for axon guidance and angiogenic factors. Systemic estradiol or vehicle were chronically injected to prepubertal rats and uterine and sympathetic chain sections immunostained for NRP1. Uterine semaphorin-3A mRNA was evaluated by in situ hybridization. Control sympathetic uterine-projecting neurons (1-month-old) expressed NRP1 in their somas but not in their intrauterine terminal axons. Estradiol did not affect NRP1 in the distal ganglia. However, at the entrance of the organ, some sympathetic NRP1-positive nerves were recognized. Vascular NRP1 was confined to intrauterine small-diameter vessels in both hormonal conditions. Although the overall pattern of NRP1-IR was not affected by E2 treatment, a subpopulation of infiltrated eosinophil leukocytes showed immunoreactivity for NRP1. Sema3A transcripts were detected in this cellular type as well. No NRP1-immunoreactive axons nor infiltrated eosinophils were visualized in other estrogenized pelvic organs. Together, these data suggest the involvement of NRP1/Sema3A signaling in the selective E2-induced uterine neurovascular remodeling. Our data support a model whereby NRP1 could coordinate E2-induced uterine neurovascular remodeling, acting as a positive regulator of growth when expressed in vessels and as a negative regulator of growth when expressed on axons.

中文翻译：

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Neuropilin-1 受体在快速和选择性雌激素诱导的大鼠子宫神经血管重塑中的作用

交感神经支配大多数器官并调节器官血流。具体而言，在子宫内，雌二醇 (E2) 会引起交感神经轴突的快速退化并刺激血管的生长。对生殖至关重要的两种生理重塑过程都已被广泛研究，但作为独立事件，仍未完全了解。在这里，我们检查neuropilin-1 (NRP1)，轴突引导和血管生成因子的共享受体。全身雌二醇或载体长期注射到青春期前的大鼠和子宫和交感神经链部分，对 NRP1 进行免疫染色。通过原位杂交评估子宫信号素-3A mRNA。对照交感神经子宫投射神经元（1 个月大）在其胞体中表达 NRP1，但在其子宫内末端轴突中不表达。雌二醇不影响远端神经节中的 NRP1。然而，在器官的入口处，识别出一些交感神经 NRP1 阳性神经。在两种激素条件下，血管 NRP1 都局限于宫内小直径血管。尽管 NRP1-IR 的整体模式不受 E2 处理的影响，但浸润的嗜酸性粒细胞白细胞亚群显示出对 NRP1 的免疫反应性。在这种细胞类型中也检测到 Sema3A 转录本。在其他雌激素化的盆腔器官中未观察到 NRP1 免疫反应性轴突或浸润的嗜酸性粒细胞。总之，这些数据表明 NRP1/Sema3A 信号参与选择性 E2 诱导的子宫神经血管重塑。我们的数据支持 NRP1 可以协调 E2 诱导的子宫神经血管重塑的模型，