Colombelli Ketlin T, Santos Sérgio A A, Camargo Ana C L, Constantino Flávia B, Barquilha Caroline N, Rinaldi Jaqueline C, Felisbino Sérgio L, Justulin Luis A
Department of Morphology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil.
Department of Morphology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil.
Gen Comp Endocrinol. 2017 May 15;246:258-269. doi: 10.1016/j.ygcen.2016.12.016. Epub 2016 Dec 29.
Experimental data demonstrated the negative impact of maternal protein malnutrition (MPM) on rat prostate development, but the mechanism behind the impairment of prostate growth has not been well understood. Male Sprague Dawley rats, borned to dams fed a normal protein diet (CTR group, 17% protein diet), were compared with those borned from dams fed a low protein diet (6% protein diet) during gestation (GLP group) or gestation and lactation (GLLP). The ventral prostate lobes (VP) were removed at post-natal day (PND) 10 and 21, and analyzed via different methods. The main findings were low birth weight, a reduction in ano-genital distance (AGD, a testosterone-dependent parameter), and an impairment of prostate development. A delay in prostate morphogenesis was associated with a reduced testosterone levels and angiogenic process through downregulation of aquaporin-1 (AQP-1), insulin/IGF-1 axis and VEGF signaling pathway. Depletion of the microvascular network, which occurs in parallel to the impairment of proliferation and differentiation of the epithelial cells, affects the bidirectional flux between blood vessels impacting prostatic development. In conclusion, our data support the hypothesis that a reduction in microvascular angiogenesis, especially in the subepithelial compartment, is associated to the impairment of prostate morphogenesis in the offspring of MPM dams.
实验数据表明母体蛋白质营养不良（MPM）对大鼠前列腺发育有负面影响，但前列腺生长受损背后的机制尚未完全明确。将出生于喂食正常蛋白质饮食（对照组，17%蛋白质饮食）母鼠的雄性斯普拉格-道利大鼠，与在妊娠期（GLP组）或妊娠期和哺乳期（GLLP）由喂食低蛋白质饮食（6%蛋白质饮食）母鼠所生的大鼠进行比较。在出生后第10天和21天切除腹侧前列腺叶（VP），并通过不同方法进行分析。主要发现为低出生体重、肛门生殖器距离（AGD，一个依赖睾酮的参数）缩短以及前列腺发育受损。前列腺形态发生延迟与睾酮水平降低以及通过水通道蛋白-1（AQP-1）、胰岛素/胰岛素样生长因子-1轴和血管内皮生长因子（VEGF）信号通路下调导致的血管生成过程受损有关。微血管网络的耗竭与上皮细胞增殖和分化受损同时发生，影响血管之间的双向通量，进而影响前列腺发育。总之，我们的数据支持这样一种假说，即微血管生成减少，尤其是上皮下区域的微血管生成减少，与MPM母鼠后代前列腺形态发生受损有关。
