Spiegelhoff Audrey, Wang Kathy, Ridlon Monica, Lavery Thomas, Kennedy Conner L, George Serena, Stietz Kimberly P Keil
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison, Madison, WI 53706, USA.
Toxics. 2023 Jul 13;11(7):609. doi: 10.3390/toxics11070609.
Polychlorinated biphenyls (PCBs) are persistent organic pollutants linked to deleterious health outcomes, including voiding dysfunction in developmentally exposed mice. Changes in prostate volume and/or extracellular matrix composition are associated with voiding dysfunction in men and animal models. Whether PCB-induced changes in voiding function in male mice occur in part via alterations to the prostate or an alternate mechanism is unclear. Therefore, we tested whether developmental exposure to the MARBLES PCB mixture altered prostate morphology in young adult offspring. C57Bl/6J female mice were dosed daily with the MARBLES PCB mixture at 0, 0.1, 1 or 6 mg/kg/d for two weeks prior to mating and through gestation and lactation, offspring were collected at 6 weeks of age. Ventral prostate mass was decreased in the 1 mg/kg/d PCB group compared to other PCB groups. There were no PCB-induced changes in prostate smooth muscle thickness, apoptosis, proliferation, or testes mass. PCBs impacted the prostate extracellular matrix; anterior prostate collagen density was decreased in the 1 mg/kg/d PCB group compared to all other groups. Normalized bladder volume was increased in male and female offspring in the 6 mg/kg/d PCB group compared to control. No change in water consumption, bladder mass or bladder smooth muscle thickness accompanied changes in bladder volume. Urine and serum creatinine concentrations were elevated but only in male mice. Together, these results suggest that developmental exposure to PCBs can influence prostate wet weight and prostate/bladder morphology, but PCBs do not promote prostate enlargement. Whether these changes persist throughout adult life and how they contribute to voiding function in animal models and humans is of future interest.
多氯联苯(PCBs)是持久性有机污染物,与有害健康后果相关,包括发育过程中接触多氯联苯的小鼠出现排尿功能障碍。前列腺体积和/或细胞外基质组成的变化与男性及动物模型中的排尿功能障碍有关。目前尚不清楚多氯联苯诱导的雄性小鼠排尿功能变化是否部分通过前列腺改变或其他机制发生。因此,我们测试了发育过程中接触多氯联苯混合物MARBLES是否会改变成年幼崽的前列腺形态。C57Bl/6J雌性小鼠在交配前两周及整个妊娠期和哺乳期每天给予0、0.1、1或6mg/kg/d的多氯联苯混合物MARBLES,在幼崽6周龄时收集样本。与其他多氯联苯组相比,1mg/kg/d多氯联苯组的腹侧前列腺质量降低。多氯联苯对前列腺平滑肌厚度、细胞凋亡、增殖或睾丸质量没有诱导性变化。多氯联苯影响前列腺细胞外基质;与所有其他组相比,1mg/kg/d多氯联苯组的前前列腺胶原密度降低。与对照组相比,6mg/kg/d多氯联苯组的雄性和雌性幼崽的标准化膀胱体积增加。膀胱体积变化时,饮水量、膀胱质量或膀胱平滑肌厚度没有变化。尿液和血清肌酐浓度升高,但仅在雄性小鼠中出现。总之,这些结果表明,发育过程中接触多氯联苯会影响前列腺湿重和前列腺/膀胱形态,但多氯联苯不会促进前列腺增大。这些变化是否在成年期持续存在,以及它们如何影响动物模型和人类的排尿功能,是未来研究的关注点。