Oleanolic acid causes reversible contraception in male mice by increasing the permeability of the germinal epithelium
David Fisher A C , Faizel Mosaval A , Darla L. Tharp B , Doug K. Bowles B and Ralf Henkel A
+ Author Affiliations
- Author Affiliations
A University of the Western Cape, Department of Medical Bioscience, Private Bag X17, Bellville 7535, South Africa.
B University of Missouri, Biomedical Sciences, 1600 E Rollins Street, Columbia, MO 65211, USA.
C Corresponding author. Email: dfisher@uwc.ac.za; davidwfisher333@gmail.com
Reproduction, Fertility and Development 31(10) 1589-1596 https://doi.org/10.1071/RD18484
Submitted: 29 November 2018 Accepted: 9 April 2019 Published: 10 May 2019
Abstract
The effects of oleanolic acid (OA) on the fertility of male mice were investigated using both in vivo and in vitro experimental models. The experimental group (n = 12) was treated with a daily dose of 30 mg OA kg−1 bodyweight (i.p.), while the control group (n = 6) received a daily dose of 10% ethanol solution (1 mL kg−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, 200 µg L−1) treated monolayers developed TER of approximately 100 Ω.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.
Additional keywords: claudin-11, occludin, paracellular permeability, tight junctions, TM4 cells, transepithelial electrical resistance.
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