Department of Pharmacology and Toxicology, College of Pharmacy, University of Arizona, Tucson, Arizona, USA.
Reproduction. 2018 Dec;156(6):R187-R194. doi: 10.1530/REP-18-0338.
The blood-testis barrier protects developing germ cells by limiting the entry of xenobiotics into the adluminal compartment. There is strong evidence that the male genital tract can serve as a sanctuary site, an area of the body where tumors or viruses are able to survive treatments because most drugs are unable to reach therapeutic concentrations. Recent work has classified the expression and localization of endogenous transporters in the male genital tract as well as the discovery of a transepithelial transport pathway as the molecular mechanism by which nucleoside analogs may be able to circumvent the blood-testis barrier. Designing drug therapies that utilize transepithelial transport pathways may improve drug disposition to this sanctuary site. Strategies that improve disposition into the male genital tract could reduce the rate of testicular relapse, decrease viral load in semen, and improve therapeutic strategies for male fertility.
血睾屏障通过限制异物进入腔室来保护发育中的生殖细胞。有强有力的证据表明,男性生殖道可以作为避难所,即身体的某个区域,肿瘤或病毒能够在那里存活下来,因为大多数药物无法达到治疗浓度。最近的工作已经对男性生殖道中内源性转运体的表达和定位以及跨上皮转运途径的发现进行了分类,这是核苷类似物能够规避血睾屏障的分子机制。设计利用跨上皮转运途径的药物治疗方法可能会改善药物对该避难所的处置。改善进入男性生殖道的处置策略可以降低睾丸复发率、减少精液中的病毒载量,并改善男性生育力的治疗策略。