Oleanolic acid causes reversible contraception in male mice by increasing the permeability of the germinal epithelium

Abstract

The effects of oleanolic acid (OA) on the fertility of male mice were investigated using both invivo and invitro experimental models. The experimental group (n=12) was treated with a daily dose of 30mgOAkg−1 bodyweight (i.p.), while the control group (n=6) received a daily dose of 10% ethanol solution (1mLkg−1 bodyweight). The effect of OA on the permeability status of TM4 Sertoli monolayers was investigated by measuring the transepithelial electrical resistance (TER), intracellular electrical resistance and semiquantitative RT–PCR. After 45 days, OA-treated males produced no pregnancies but in the control group, all 12 females were impregnated (69 offspring). Male mice, which demonstrated sterility when exposed to OA, recovered their fertility after 30 days (78 offspring). Testicular histological observations of OA-treated mice showed detachment of adjacent Sertoli–Sertoli cells. A control monolayer developed TER of 300–400 Ω.cm2, but OA (50, 100, 200µgL−1) treated monolayers developed TER of approximately 100Ω.cm2. Intracellular electrophysiological and RT–PCR data supported the premise that OA compromised tight junctional permeability. The study demonstrated reversible contraception in male mice by increasing the permeability of the germinal epithelium and further postulates that contraceptive reversibility is brought about by the reconstitution of the paracellular junctions between adjacent Sertoli cells.