Date of Award:

5-1-1983

Document Type:

Thesis

Degree Name:

Master of Science (MS)

Department:

Biology

Department name when degree awarded

Life Sciences:Biology

Committee Chair(s)

Nabil N. Youssef

Committee

Nabil N. Youssef

Abstract

AF1312/TS, an antifertility agent synthesized by Silvestrini and associates in Italy, has the potential to be developed as a contraceptive in human males. This chemical's action is extremely specific, affecting initially, only the elements of the seminiferous epithelium. The drug's action is reversible, and dose, and species specific. This study was undertaken to observe the general morphplogical changes in the testis and epididymis of the mouse due to oral dosing with AF1312/TS. Damage was so drastic, it was evident with the light microscope. Fine structural analysis was used to determine the cell types involved, as well as the organelles damaged within those cell types. In two experiments, different doses, dosing lengths, and tissue sampling times were used. The dosing was intended to simulate an oral contraceptive. In the first experiment, sampling was done at the end of dosing to observe the maximal effect. In the second experiment, samples were taken continuously through the dosing to follow the effect of the drug through time. Breeding trails were run to test the biological effectiveness of AF1312/TS as a contraceptive and its reversibility. This study supports the previous works, which found Sertoli cells to be at the center of the drug's action. Blood-testis barrier disruption was observed very early, and may mediate further damage to the adluminal compartment of the seminferous epithelium. Although no damage was observed in the epididymal epithelium, spermatozoa within the epididymal duct were rendered infertile with higher doses. This effect is probably secondary to Sertoli cell damage.

Share

COinS