Effects of the prostanoid receptor antagonist, di-4-phloretin phosphate, upon human sperm motility
Ratnasooriya, W.D.; Premakumara, G.A.
Contraception 45(3): 239-248
1992
ISSN/ISBN: 0010-7824 PMID: 1511609 DOI: 10.1016/0010-7824(92)90068-5Document Number: 318082
The effect of the prostanoid receptor antagonist, di-4-phloretin PO4, (DPP, Leo Akteibolaget, Helsingborg, Sweden) on percent motility and forward velocity of washed human sperm was investigated. Semen specimens were collected after 305 days of abstinence, allowed to liquefy at room temperature for 15-25 minutes, and washed 3 times in modified Krebs-Ringer bicarbonate buffer. Standardized sperm suspensions were incubated for 60 minutes with DPP, and tested at concentrations form 0.01 to 10.0 mM, all of which halted sperm movement irreversibly. The mean concentration immobilizing 50% of sperm was 1.31 mM, and stopping 50% mean forward velocity, 1.95mM. Experiments aimed at pinpointing the mechanism of action of DPP showed that at medium to high concentrations, 2.5-10 mM, DPP caused hypo-osmotic swelling, an indicator if impaired sperm plasmalemma function, and nigrosin-eosin uptake, a sign of loss of viability. There was no evidence of a physical disruption of the sperm plasma membrane, assessed by leakage of the enzyme glutamic oxaloacetic transaminase (GOT). Experiments were also run in medium with or without caffeine and calcium. DPP 0.25 mM slowed motility significantly (p0.05) in normal and Ca++ free medium after 15 minutes. Caffeine enhanced motility in normal medium, but cont Ca++ free medium. DPP impaired motility somewhat in normal medium containing caffeine, but no in Ca++ free medium with caffeine. These results may indicate that DPP works by mobilizing intracellular Ca++, or by decreasing the level of cyclic AMP.