Pytlowanciv Eloísa Zanin, Pinto-Fochi Maria Etelvina, Reame Vanessa, Gobbo Marina Guimarães, Ribeiro Daniele Lisboa, Taboga Sebastião Roberto, Góes Rejane Maira
Department of Structural and Functional Biology, Institute of Biology, Campinas State University-UNICAMP, Campinas, São Paulo, Brazil.
Department of Biology, Institute of Biosciences, Letters and Exact Sciences, Univ Estadual Paulista-UNESP, São José do Rio Preto, São Paulo, Brazil.
Prostate. 2016 May;76(7):662-78. doi: 10.1002/pros.23158. Epub 2016 Feb 5.
Experimental data indicate that high-fat diet (HFD) may alter proliferative activity and prostate health. However, the consequences of HFD exposure during different periods of ontogenetic development on prostate histophysiology remain to be elucidated. Herein, we compare the influence of obesogenic environment (OE) due to maternal obesity and HFD at different periods of life on proliferative activity and nuclear receptors frequency in the rat ventral prostate and a possible relationship with metabolic and hormonal alterations.
Male Wistar rats (19 weeks old), treated with balanced chow (Control group-C; 3% high-fat, 3.5 Kcal/g), were compared with those exposed to HFD (20% high-fat, 4.9 kcal/g) during gestation (G-maternal obesity), gestation and lactation (GL), from post-weaning to adulthood (WA), from lactation to adulthood (LA) and from gestation to adulthood (GA). After the experimental period, the ventral prostate lobes were removed and analyzed with different methods.
Metabolic data indicated that G and GL rats became insulin resistant and WA, LA, and GA became insulin resistant and obese. There was a strong inverse correlation between serum testosterone (∼133% lower) and leptin levels (∼467% higher) in WA, LA, and GA groups. Estrogen serum levels increased in GA, and insulin levels increased in all groups, especially in WA (64.8×). OE-groups exhibited prostatic hypertrophy, since prostate weight increased ∼40% in G, GL, LA, and GA and 31% in WA. As indicated by immunohistochemistry, all HFD-groups except G exhibited an increase in epithelial cell proliferation (PCNA-positive) and a decrease in frequency of AR- and ERβ-positive epithelial cells; there was also an increment of ERα-positive stromal cells in comparison with control. Cells containing PPARγ increased in both epithelium and stroma of all OE groups and those expressing LXRα decreased, particularly in groups OE-exposed during gestation (G, GL and GA).
OE leads to prostate hypertrophy regardless of the period of development and, except when restricted to gestation, leads to a hyperproliferative status which was correlated to downregulation of AR and LXRα and upregulation of ERα and PPARγ signaling.
实验数据表明，高脂饮食（HFD）可能会改变增殖活性和前列腺健康。然而，在个体发育的不同时期暴露于高脂饮食对前列腺组织生理学的影响仍有待阐明。在此，我们比较了由于母体肥胖和不同生命时期的高脂饮食导致的致肥胖环境（OE）对大鼠腹侧前列腺增殖活性和核受体频率的影响，以及与代谢和激素改变的可能关系。
将雄性Wistar大鼠（19周龄）分为对照组（C组，给予平衡饲料，3%高脂肪，3.5千卡/克），与在妊娠期间（G组 - 母体肥胖）、妊娠和哺乳期（GL组）、断奶后至成年期（WA组）、哺乳期至成年期（LA组）以及妊娠至成年期（GA组）暴露于高脂饮食（20%高脂肪，4.9千卡/克）的大鼠进行比较。实验期结束后，切除腹侧前列腺叶并用不同方法进行分析。
代谢数据表明，G组和GL组大鼠出现胰岛素抵抗，WA组、LA组和GA组大鼠出现胰岛素抵抗且肥胖。在WA组、LA组和GA组中，血清睾酮水平（降低约133%）与瘦素水平（升高约467%）之间存在强烈的负相关。GA组雌激素血清水平升高，所有组胰岛素水平均升高，尤其是WA组（升高64.8倍）。OE组出现前列腺肥大，因为G组、GL组、LA组和GA组前列腺重量增加约40%，WA组增加31%。免疫组织化学结果显示，除G组外，所有高脂饮食组上皮细胞增殖（PCNA阳性）增加，AR和ERβ阳性上皮细胞频率降低；与对照组相比，ERα阳性基质细胞也增加。所有OE组上皮和基质中含PPARγ的细胞增加，表达LXRα的细胞减少，特别是在妊娠期间暴露于OE的组（G组、GL组和GA组）。
无论发育时期如何，OE均导致前列腺肥大，且除仅限于妊娠外，还导致增殖过度状态，这与AR和LXRα的下调以及ERα和PPARγ信号的上调相关。
