G.P. Kumar

REGIONAL HETEROGENEITY IN INTRACELLULAR DISTRIBUTION OF SUPEROXIDE AND HYDROGEN PEROXIDE WITHIN THE SPERM AND ITS RELATION TO SPERM DEVELOPMENT

This study was performed to understand the regional distribution of superoxide anion radicals and hydrogen peroxide within the spermatozoa of mice during both normal and altered situations of epididymal maturation. The intracellular O2*- levels were probed employing dichlorodihydrofluorescein diacetate (DDF) as a reporter. The testicular spermatozoa from normal animals showed strong regional heterogeneity in the DDF fluorescence patterns over the various domains. Vasectomy resulted in strong inhibition in the O2* levels of spermatozoa at all stages of maturation. Interestingly, the fluorescein diacetate staining pattern was strong in the head of spermatozoa from the testis, caput, corpus, and cauda region. Further. there was a progressive reduction in the fluorescence in the head region in the spermatozoa toward the cauda region. The midpiece and tail showed moderate fluorescence, which also diminished as the spermatozoa matured. The spermatozoa from the vas deferens exhibited a weak fluorescence over the head domain, with the other domain staining extremely weak. Here again, vasectomy introduced considerable loss in the fluorescence intensity. The implications of programmed production of reactive oxygen species in specific domains of the spermatozoa during various stages of development are discussed.

Neutralization of pregnancy-preventing activity of cabergoline, a dopamine agonist with progesterone.

Cabergoline (Cab), a dopamine agonist, inhibits the production and/or release of prolactin and reduces progesterone biosynthesis. Cab at doses of 20 microg/kg/d and higher administered on Days 1, 2 and 3 of pregnancy prevented implantation of fertilized ova in all treated female rats. The pregnancy-preventing activity of Cab is attributed to a deficiency of progesterone since estradiol levels remain unchanged. To validate the hypothesis that progesterone deficiency is the cause of the infertility, exogenous progesterone was administered to Cab-treated pregnant female rats and their fertility assessed. Progesterone at a dose of 5 mg/kg/d sc was administered on Days 1 to 7 of pregnancy to female rats treated with Cab (20 and 60 microg/kg/d) on Days 1, 2 and 3 of pregnancy. All progesterone-treated animals became pregnant, and all mated female rats treated with Cab (60 microg/kg/d) and progesterone (5 mg/kg/d) on Days 1 to 7 inclusive became pregnant. In conclusion, progesterone can neutralize the pregnancy preventing activity of Cab. Pregnant female rats treated with Cab can be used to assay for progestagenic activity of compounds.