Laboratory of Cell Biology, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida Italia 3318, ZP 11600, Montevideo, Uruguay.
Department of Experimental Neuropharmacology, Instituto de Investigaciones Biológicas Clemente Estable (IIBCE), Avenida Italia 3318, ZP 11600, Montevideo, Uruguay.
Cell Tissue Res. 2020 Aug;381(2):299-308. doi: 10.1007/s00441-020-03196-8. Epub 2020 Apr 2.
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.
交感神经支配着大多数器官，并调节器官的血液流动。具体来说，在子宫中，雌二醇（E2）引起交感神经轴突的快速退化，并刺激血管生长。这两个对生殖至关重要的生理重塑过程已经被广泛研究，但作为独立事件，它们仍未被完全理解。在这里，我们研究了神经纤毛蛋白-1（NRP1），这是一种轴突导向和血管生成因子的共同受体。将雌二醇或载体系统地注射到青春期前的大鼠中，并对子宫和交感神经链切片进行 NRP1 免疫染色。通过原位杂交评估子宫 Sema3A mRNA。对照性的、向子宫投射的交感神经元（1 个月大）在其体部表达 NRP1，但不在其子宫内终末轴突中表达。E2 对远节神经节中的 NRP1 没有影响。然而，在器官的入口处，可以识别到一些交感 NRP1 阳性神经。血管 NRP1 局限于子宫内的小直径血管，无论激素条件如何。尽管 E2 处理并没有影响 NRP1 的整体免疫反应模式，但一些浸润的嗜酸性白细胞表现出 NRP1 的免疫反应性。这种细胞类型也检测到 Sema3A 转录物。在其他雌激素化的骨盆器官中，没有观察到 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 信号参与了 E2 诱导的子宫神经血管重塑的选择性。我们的数据支持一种模型，即 NRP1 可以协调 E2 诱导的子宫神经血管重塑，当在血管中表达时作为生长的正调节剂，而当在轴突中表达时作为生长的负调节剂。
