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W. Löscher, H. Lüttgenau, W. Schlegel and S. Krüger

Summary. The pharmacokinetics of various non-steroidal anti-inflammatory drugs were determined to find dosage regimens by which drug concentrations known as active from human anti-inflammatory therapy could be reached and maintained in rabbits during continued administration. Based on the pharmacokinetics and side-effects of the different drugs, phenylbutazone was selected for the fertility experiments. Treatment of male rabbits with phenylbutazone for 9 consecutive days significantly reduced seminal concentrations of PGE-2 and PGF-2α and tended to increase ejaculate volumes, sperm motility, and fertility. These results indicate that, at least in rabbits, inhibition of PG synthesis by prolonged treatment with non-steroidal anti-inflammatory drugs does not impair male fertility. Instead, chronic treatment with the drugs at non-toxic doses may improve sperm quality and fertility.

Keywords: prostaglandins; anti-inflammatory drugs; rabbits; male fertility

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W. Schlegel, B. Fischer, H. M. Beier and H. P. G. Schneider

Summary. PGE-2 and PGF-2α in rabbit semen were selectively inactivated by incubation with antisera, or most of the seminal prostaglandins were transformed into biologically inactive 15-keto-prostaglandins by prostaglandin-15-hydroxydehydrogenase (PG-15-HDH). These treated ejaculates were vaginally inseminated. Compared to the controls (738 eggs of which 94% were fertilized) a dose-dependent reduction of the fertilization rate was observed with the anti-PGF-2α-treated ejaculates. A nonuniformly, but statistically significantly reduced fertility was found in the other 2 treatment groups. After incubation with higher doses of PG-15-HDH, some fertilization was accomplished with ejaculates showing an extremely weak forward progression or immotile spermatozoa. An improvement in sperm motility, however, was observed in ejaculates treated with antiserum to PGF-2α. Seminal prostaglandins may not exclusively affect sperm motility. The observed influences on the fertilization rate after treatment of spermatozoa with antisera to PGE-2 and PGF-2α or PG-15-HDH suggest that these are local effects in the female genital tract.

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W. Schlegel, S. Krüger, D. Daniels, B. Fischer, H. P. G. Schneider and H. M. Beier

Summary. Corpora lutea and ovarian stromal tissue were anlaysed for prostaglandin (PG) concentrations and activities of enzymes involved in PG metabolism at 8, 10, 12, 13 and 15 days after induction of ovulation. In CL of pseudopregnant rabbits, the PGE-2–9-ketoreductase (PGE-2–9-KR) was highly active on Days 10, 12 and 15 when compared with Day 8 (P < 0·01; P < 0·001; P < 0·05). In pregnant animals PGE-2–9KR activity was only increased on Day 12 (P < 0·05) but declined to basal levels on Days 13 and 15. Comparing PGE-2–9-KR activity of pseudopregnant and pregnant animals, a significant elevation was found on Day 15 of pseudopregnancy (P < 0·025). Activities of PG-15-hydroxydehydrogenase did not exhibit any significant changes with time in pseudopregnant or pregnant rabbits.

PGE-2 concentrations were increased on Days 12, 13 and 15 (P < 0·025) when compared with Day 8. Changes in PGF-2α concentrations paralleled those of PGE-2–9-KR. The concentrations of PG metabolites 13,14-dihydro-15-keto-PGE-2 and -PGF-2α were lower than those of the primary PGs and did not show stage-specific changes in pseudopregnant and pregnant animals.

These results demonstrate that the rabbit CL posesses enzymes to convert PGE-2 to PGF-2α and to metabolize both PGs. PGE-2–9-KR may be involved in regulating the PGF-2α/PGE-2 ratio and possibly in controlling the life-span of the corpus luteum.

Keywords: PGE-2-9-ketoreductase; prostaglandin-15-hydroxydehydrogenase; luteolysis; prostaglandin metabolism; pseudopregnancy; rabbit