Kennedy Conner L, Spiegelhoff Audrey, Lavery Thomas, Wang Kathy, Manuel Robbie Sj, Wang Zunyi, Wildermuth Hannah, Keil Stietz Kimberly P
Department of Comparative Biosciences, School of Veterinary Medicine, University of Wisconsin-Madison Madison, WI 53706, USA.
Department of Surgical Sciences, School of Veterinary Medicine, University of Wisconsin-Madison Madison, WI 53706, USA.
Am J Clin Exp Urol. 2022 Apr 15;10(2):82-97. eCollection 2022.
The impact of developmental exposure to environmental chemicals on lower urinary tract function is not well understood, despite the fact that these chemicals could contribute to etiologically complex lower urinary tract symptoms (LUTS). Polychlorinated biphenyls (PCBs) are environmental toxicants known to be detrimental to the central nervous system, but their impact on voiding function in mouse models is not known. Therefore, we test whether developmental exposure to PCBs is capable of altering voiding physiology in young adult mice. C57Bl/6J female mice received a daily oral dose of the MARBLES PCB mixture for two weeks prior to mating and through gestation and lactation. The mixture mimics the profile of PCBs found in a contemporary population of pregnant women. Voiding function was then tested in young adult offspring using void spot assay, uroflowmetry and anesthetized cystometry. PCB effects were sex and dose dependent. Overall, PCBs led to increases in small size urine spots in both sexes with males producing more drop-like voids and greater peak pressure during a voiding cycle while females displayed decreases in void duration and intervoid interval. Together, these results indicate that developmental exposure to PCBs are capable of altering voiding physiology in young adult mice. Further work to identify the underlying mechanisms driving these changes may help develop more effective preventative or therapeutic strategies for LUTS.
尽管环境化学物质可能导致病因复杂的下尿路症状(LUTS),但发育过程中接触环境化学物质对下尿路功能的影响尚未得到充分了解。多氯联苯(PCBs)是已知对中枢神经系统有害的环境毒物,但其对小鼠模型排尿功能的影响尚不清楚。因此,我们测试发育过程中接触多氯联苯是否能够改变年轻成年小鼠的排尿生理。C57Bl/6J雌性小鼠在交配前两周以及整个妊娠期和哺乳期每天口服MARBLES多氯联苯混合物。该混合物模拟了当代孕妇群体中发现的多氯联苯特征。然后使用排尿斑点试验、尿流率测定法和麻醉膀胱测压法对年轻成年后代的排尿功能进行测试。多氯联苯的影响具有性别和剂量依赖性。总体而言,多氯联苯导致两性中小尺寸尿斑增多,雄性在排尿周期中产生更多点滴状排尿且峰值压力更大,而雌性的排尿持续时间和排尿间隔时间缩短。总之,这些结果表明发育过程中接触多氯联苯能够改变年轻成年小鼠的排尿生理。进一步确定驱动这些变化的潜在机制的工作可能有助于开发更有效的LUTS预防或治疗策略。