Department of Structural and Functional Biology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil.
Department of Structural and Functional Biology, Institute of Biosciences, Sao Paulo State University, Botucatu, SP, Brazil; Snyder Institute for Chronic Diseases, Cumming School of Medicine, University of Calgary, Alberta, Canada.
Mol Cell Endocrinol. 2021 Mar 1;523:111148. doi: 10.1016/j.mce.2020.111148. Epub 2020 Dec 31.
The concept of Developmental Origins of Health and Disease (DOHaD) states that exposure to malnutrition early in life increase the incidence of non-communicable chronic diseases throughout the lifespan. In this study, a reduction in serum testosterone and an increase in estrogen levels were shown in older rats born to protein malnourished dams (6% protein in the diet) during gestation and lactation. Intraprostatic levels of reduced glutathione were decreased, while tissue expression of glutathione S-transferase pi and sulfiredoxin-1 were increased in these animals. Strong immunostaining for alfametilacil CoA racemase (AMACR), vascular endothelial growth factor-A (VEGF-A), and aquaporin-1 (AQP1) was also observed. In silico analysis confirmed commonly deregulated proteins in the ventral prostate of old rats and patients with prostate cancer. In conclusion, the increase in oxidative stress associated with an imbalance of sex hormones may contribute to prostate carcinogenesis in offspring, highlighting early-life malnutrition as a key risk factor for this malignance.
健康与疾病的发育起源（DOHaD）概念表明，生命早期的营养不良暴露会增加整个生命周期中非传染性慢性疾病的发病率。在这项研究中，在妊娠和哺乳期，饮食中蛋白质含量为 6%的蛋白质营养不良母鼠所生的老年大鼠的血清睾丸酮水平降低，而雌激素水平升高。这些动物的前列腺内还原型谷胱甘肽水平降低，谷胱甘肽 S-转移酶 pi 和 sulfiredoxin-1 的组织表达增加。α-甲酰基辅酶 A 消旋酶（AMACR）、血管内皮生长因子-A（VEGF-A）和水通道蛋白-1（AQP1）的免疫染色也很强。计算机分析证实了老年大鼠和前列腺癌患者前列腺腹侧中常见的失调蛋白。总之，与激素失衡相关的氧化应激增加可能导致后代的前列腺癌发生，强调生命早期的营养不良是这种恶性肿瘤的关键危险因素。
