Physiologie de la Reproduction et des Comportements PRC Centre INRAE Val de Loire, CNRS, IFCE, INRAE, Université de Tours, 37380, Nouzilly, France.
Histochem Cell Biol. 2022 May;157(5):581-593. doi: 10.1007/s00418-022-02079-z. Epub 2022 Feb 3.
Sheep, like most seasonal mammals, exhibit a cyclic adaptive reproductive physiology that allows ewes to give birth to their progeny during the spring when environmental conditions are favorable to their survival. This process relies on the detection of day length (or photoperiod) and is associated with profound changes in cellular plasticity and gene expression in the hypothalamic-pituitary-gonadal axis, mechanisms that are suggested to participate in the seasonal adaptation of neuroendocrine circuits. Recently, pituitary vascular growth has been proposed as a seasonally regulated process in which the vascular endothelial growth factor A (VEGFA), a well-known angiogenic cytokine, is suspected to play a crucial role. However, whether this mechanism is restricted to the pituitary gland or also occurs in the mediobasal hypothalamus (MBH), a crucial contributor to the control of the reproductive function, remains unexplored. Using newly developed image analysis tools, we showed that the arcuate nucleus (ARH) of the MBH exhibits an enhanced vascular density during the long photoperiod or non-breeding season, associated with higher expression of VEGFA. In the median eminence (ME), a structure connecting the MBH to the pituitary gland, higher VEGFA, kinase insert domain receptor (KDR/VEGFR2) and plasmalemma vesicle-associated protein (PLVAP) gene expressions were detected during the long photoperiod. We also found that VEGFA and its receptor, VEGFR2, are expressed by neurons and tanycytes in both the ARH and ME. Altogether, these data show variations in the MBH vasculature according to seasons potentially through a VEGFA-dependent pathway, paving the way for future studies aiming to decipher the role of these changes in the hypothalamic control of seasonal reproduction.
绵羊与大多数季节性哺乳动物一样，表现出周期性的适应性生殖生理，使母羊能够在环境条件有利于其生存的春季产仔。这个过程依赖于对日照长度（或光周期）的检测，并与下丘脑-垂体-性腺轴的细胞可塑性和基因表达的深刻变化相关联，这些机制被认为参与了神经内分泌回路的季节性适应。最近，垂体血管生长被认为是一个季节调节的过程，其中血管内皮生长因子 A（VEGFA），一种众所周知的血管生成细胞因子，被怀疑在其中发挥关键作用。然而，这种机制是否仅限于垂体，或者也发生在中脑基底部（MBH），这是生殖功能控制的关键贡献者，仍然未知。使用新开发的图像分析工具，我们发现 MBH 的弓状核（ARH）在长光照周期或非繁殖季节表现出增强的血管密度，与 VEGFA 的高表达相关。在连接 MBH 与垂体的正中隆起（ME）中，在长光照周期期间检测到更高的 VEGFA、激酶插入结构域受体（KDR/VEGFR2）和质膜小泡相关蛋白（PLVAP）基因表达。我们还发现，VEGFA 及其受体 VEGFR2 均由 ARH 和 ME 中的神经元和 tanycytes 表达。总之，这些数据表明，根据季节的不同，MBH 血管会发生变化，可能是通过 VEGFA 依赖的途径，为未来旨在解码这些变化在季节性生殖的下丘脑控制中的作用的研究铺平了道路。
