Xenobiotic transporter expression along the male genital tract

Abstract

The male genital tract plays an important role in protecting sperm by forming a distinct compartment separate from the body which limits exposure to potentially toxic substrates. Transporters along this tract can influence the distribution of xenobiotics into the male genital tract through efflux back into the blood or facilitating the accumulation of toxicants. The aim of this study was to quantitatively determine the constitutive mRNA expression of 30 xenobiotic transporters in caput and cauda regions of the epididymis, vas deferens, prostate, and seminal vesicles from adult Sprague-Dawley rats. The epididymis was found to express at least moderate levels of 18 transporters, vas deferens 15, seminal vesicles 23, and prostate 18. Constitutive expression of these xenobiotic transporters in the male genital tract may provide insight into the xenobiotics that can potentially be transported into these tissues and may provide the molecular mechanism for site specific toxicity of select agents.

Age-related testicular toxicity of mGluR5 negative allosteric modulators appears to be unrelated to testis drug transporter maturity

“…epididymis, respectively, (Fig. 7) confirm previously published work [27]. In addition, the nucleoside transporters Slc29a1 (Ent1) and Slc29a2 (Ent2) were detected at high levels in the testis (Figs.…”

“…blood testis barrier and blood brain barrier. The previously characterized expression patterns of transporters across the different tissues [26,27] were confirmed in the current study. The expression of several ABC (ATP-binding cassette) transporter family members and several nucleoside transporters is shown in Figs.…”

“…Based on these findings, immaturity of drug transporter expression does not appear to play a role in the increased incidence of testis lesions in younger Wistar rats, although potential differences in transporter function in these animals cannot be ruled out. While other studies have examined the expression levels of drug transporters in adult rat testis with results similar to those reported here [26,27], this is the only study examining the late ontogeny of several transporters in rat testis. Klein et al [41] evaluated the protein expression of Mrp1, Mrp4, and Mrp5 in 3 week and 12 week old Sprague-Dawley rats and found no differences in the expression between the two ages.…”

“…As discussed earlier, other studies have examined the expression levels of drug transporters in the testis and other male reproductive organs in relation to other previously characterized tissues (liver, kidney) [26,27]. The data in the current study is presented in a similar manner (expression relative to kidney levels) to allow for easier comparison to this previously published work.…”

HIV-1-RNA Decay and Dolutegravir Concentrations in Semen of Patients Starting a First Antiretroviral Regimen

“…Thus, the low penetration of DTG into the male genital tract may be explained mainly by the drug's high BP protein binding (>99%). However, total DTG seminal exposure was higher than the free drug concentration in BP, suggesting that drug uptake transporters in addition to passive diffusion of unbound drug may be implicated in DTG penetration in the male genital tract [21].…”