Breast cancer resistant protein (BCRP, ABCG2) is an ATP-binding cassette (ABC) transporter, which together
with two other ABC efflux drug pumps, namely P-glycoprotein (P-gp, ABCB1) and multidrug resistance-related protein 1
(MRP1, ABCC1) is the most important multidrug resistance protein foun d in eukaryotic cells including cells in the testis.
However, unlike P-gp and MRP1, which are components of the Sertoli cell blood-testis barrier (BTB), BCRP is not expressed
at the BTB in rodents and human testes. Instead, BCRP is expressed by peritubular myoid cells and endothelial cells of the
lymphatic vessel in the tunica propria, residing outside the BTB. As such, the testis is equipped with two levels of defense
against xenobiotics or drugs, preventing these harmful substances from entering the adluminal compartment to perturb meiosis
and post-meiotic spermatid development: one at the level of the BTB conferred by P-gp and MRP1 and one at the tunica
propria conferred by BCRP. The presence of drug transporters at the tunica propria as well as at the Sertoli cell BTB thus
poses significant obstacles in developing non-hormonal contraceptives if these drugs (e.g., adjudin) exert their effects in germ
cells behind the BTB, such as in the adluminal (apical) compartment of the seminiferous epithelium. Herein, we summarize
recent findings pertinent to adjudin, a non-hormonal male contraceptive, and molecular interactions of adjudin with BCRP so
that this information can be helpful to devise delivery strategies to evade BCRP in the tunica propria to improve its bioavailability
in the testis.