The prostate development has an important postnatal period where cell proliferation begins at the first days after birth and is related to gland growth and ramification. Any metabolic and/or hormonal changes occurring during the postnatal period can interfere with prostate branching. Hyperglycemia is a common condition in low weight preterm babies at neonatal period and also a disorder found in the offspring of obese mothers. Thus, this study aimed to investigate the in vitro effects of a glucose-rich environment during prostate postnatal development. Wistar rats prostate were removed at birth and cultured for 1, 2 and 3 days in DMEM under normal (5.5mM) or elevated (7 and 25mM) glucose concentrations. Samples were processed for morphological analysis, PCNA and smooth muscle α-actin immunohistochemistry, evaluation of active caspase-3, ERK1/2 and Wnt5a gene expression. High glucose concentrations reduced the number of prostatic buds and proliferating cells. The natural increase in smooth muscle cells and collagen deposition observed in control prostates during the first 3 days of development was reduced by elevated glucose concentrations. The amount of active caspase-3 was higher in prostates incubated at 7mM and TGF-β levels also increased sharply after both glucose concentrations. Additionally, high glucose environment decreased ERK 1/ 2 activation and increased Wnt5a expression. These data show that high levels of glucose during the first postnatal days affected prostate development by inhibiting cell proliferation which impairs bud branching and this was associated with anti-proliferative signals such as decreased ERK1/2 activation and increased Wnt5a expression.

中文翻译：

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体外高糖环境损害大鼠出生后前列腺发育

前列腺发育有一个重要的出生后时期，细胞增殖开始于出生后的第一天，并与腺体生长和分枝有关。产后期间发生的任何代谢和/或荷尔蒙变化都会干扰前列腺的分支。高血糖是新生儿期低体重早产儿的常见病症，也是肥胖母亲的后代中发现的一种疾病。因此，本研究旨在研究富含葡萄糖的环境在前列腺产后发育过程中的体外影响。Wistar 大鼠前列腺在出生时被移除，并在正常 (5.5 mM) 或升高的 (7 和 25 mM) 葡萄糖浓度下在 DMEM 中培养 1、2 和 3 天。处理样品用于形态学分析、PCNA 和平滑肌 α-肌动蛋白免疫组织化学、活性 caspase-3 的评估、ERK1/2 和 Wnt5a 基因表达。高葡萄糖浓度减少了前列腺芽和增殖细胞的数量。在发育的前 3 天，在对照前列腺中观察到的平滑肌细胞和胶原沉积的自然增加因葡萄糖浓度升高而减少。在 7 mM 孵育的前列腺中，活性 caspase-3 的量更高，并且在两种葡萄糖浓度后，TGF-β 水平也急剧增加。此外，高葡萄糖环境会降低 ERK 1/2 的激活并增加 Wnt5a 的表达。这些数据表明，出生后第一天的高水平葡萄糖通过抑制细胞增殖来影响前列腺发育，这会损害芽的分枝，这与抗增殖信号有关，例如减少 ERK1/2 激活和增加 Wnt5a 表达。