| Disease | DAILY DOSING FOR 2-30 DAYS. RESPONSE WAS MONITORED MICROSCOPICALLY ON SPERM EXTRACTED FROM TESTIS AND PROXIMAL, MIDDLE AND DISTAL EPIDIDYMIS AT REGULAR INTERVALS, DURING AAND AFTER TREATMENT, UP TO 70 DAYS.
AT THE SPERM LEVEL, THE TITLE COMPOUND HAD A SPECIFIC EFFECT ON THE MITOCHONDRIAL APPARATUS. THIS WAS EXPRESSED IN FORM OF SEGMENTAL APLASIA WHICH OCCURRED PREDOMINANTLY JUST ABOVE THE ANNULUS AND IN DEGENERATION OF INDIVIDUAL MITOCHONDRIA.
THE APLASIA WAS THE ONLY DEFECT RECOGNIZED IN SPERM EXTRACTED FROM TESTIS AND PROXIMAL EPIDIDYMIS. DISLOCATIONS OF AXIAL FIBERS WERE OBSERVED AND PROGRESSIVELY INCREASED DURING EPIDIDYMAL TRANSIT.THESE SECONDARY LESIONS INHIBITED MOTILITY COMPLETELY.
MITOCHONDRIAL DEGENERATION WAS FIRST RECOGNIZED IN STEP 18 OF SPERMIOGENESIS, A TIME WHEN THE DEVELOPMENT OF THE MITOCHONDRIAL SHEATH IS ALMOST COMPLETE. IT CONTINUED BEYOND SPERMIATION AND WAS AGGRAVATED BY PROLONGATION OF TREATMENT.
SUCH A DEGENERATION WAS NOT OBSERVED IN PRECEEDING STEPS OF SPERMATIDS, NOR IN PRECURSORS AND SERTOLI CELLS. APLASIA WAS THE RESULT OF MITOCHONDRIAL EFICIT CAUSED BY MITOCHONDRIAL DEGENERATION.
TO TEST THE HYPOTHESIS THAT THE UNCOUPLING EFFECT OF GOSSYPOL WAS RESPONSIBLE FOR THE STRUCTURAL DAMAGE, RATS WERE TREATED WITH DICOUMAROL. THIS TREATMENT ALSO INDUCED APLASIA BUT NOT TO THE SAME EXTENT.
IN ADDITION TO SPECIFIC SPERM LESIONS, GOSSYPOL RETARDED BODY GROWTH AND CAUSED AN ATROPHY OF ACCESSORY SEX GLANDS. IT REDUCED THE WEIGHTS OF TESTIS AND EPIDIDYMIDES BY CA. 39% AND 35%,RESPECTIVELY,WHEN THE TREATMENT WAS PROLONGED (30 DAYS).
THE DROP IN TESTICULAR WEIGHT CORRELATED WITH A LOSS OF GERM CELLS. LIGHT AND ELECTRON MICROSCOPY REVEALED MARKED DEGENERATION OF MID-PACHYTENE SPERMATOCYTES(STAGE VII) AND SPERMATIDS IN STEP 7.
ALTHOUGH THE DEGENERATION WAS NOT AS CONSPICUOUS AS ABOVE, THESE WAS A SIGNIFICANT DECREASE IN NUMBER OF PRELEPTOTENE SPERMATOCYTES (STAGE VII TO VIII). AN EXFOLIATION OF SPERMATIDS, NOTICEABLY BEGINNING FROM STEP 6 ONWARDS,WAS A COMMON PHENOMENON.
SERTOLI CELLS SHOWED PRLIFERATION OF LYSOSOMES, ACCUMULATION OF LIPIDS AND MARKED VACUOLATION.
WEIGHT LOSS IN ANDROGEN TARGET ORGANS AND REDUCTIONS OF GERM CELL NUMBER, ESPECIALLY IN STAGE VII OF THE CYCLE, LED THE INVESTIGATIONS TO BELIEVE THAT GOSSYPOL EXHIBITS AN ANTIANDROGEN EFFECT. |