DIFFERENTIAL RESPONSES OF HUMAN SPERM TO VARYING CONCENTRATIONS OF PENTOXYFYLLINE WITH DEMONSTRATION OF TOXICITY

Pentoxyfylline (PF), a methylxanthine derivative, is an inhibitor of t he cAMP-phosphodiesterase enzyme, and is known to stimulate the motili ty of fresh and post-thaw human sperm. The purpose of this study was t o examine the effects of different concentrations of PF on motility (M OT), path (curvilinear) velocity (PV), and hyperactivation (HA) of fre sh sperm from patients (n = 24) and donors (n = 6) and post-thaw donor sperm (n = 5). For cryopreservation, the donor semen was frozen in li quid nitrogen using test-yolk-glycerol cryopreservative, stored for a minimum of 48 hours, then thawed at room temperature prior to assay. A liquots of all samples to equal 10 x 10(6)/ml were diluted in 1 mi of the following: medium (human tubal fluid) only (control), or 2.5, 5, 1 0, or 20 mg/ml PF in medium. Specimens were incubated at 37 degrees C, and all were assessed by computer-assisted motion analysis at 0, 0.5, 1, and 2 hours. The patient specimens were divided into two groups: g roup 1, mean percent (standard deviation [SD]) MOT <20% (12.8 +/- 5.8) ; group 2, mean percent (SD) MOT >20% (37.8 +/- 14). For fresh donor s perm, 2.5 mg/ml PF significantly stimulated PV and HA at 0, 1, and 2 h ours, and MOT at 0, 0.5, and 2 hours. PF at 5 mg/ml resulted in a decr eased PV and HA, whereas MOT was decreased by 10 mg/mi. In the <20% MO T group, 2.5 mg/ml PF significantly stimulated MOT at 0.5, 1, and 2 ho urs, and HA at 0 and 2 hours. There was no effect on PV. For group 2 ( >20% motility group), 2.5 mg/ml PF significantly stimulated PV at 0.5, 1, and 2 hours, and HA at 0.5 and 2 hours. There was no effect on MOT . For PT donor sperm, 2.5 mg/ml PF significantly stimulated MOT at 0 a nd 0.5 hours, and HA at 0.5, 1, and 2 hours. All parameters decreased with 5 and 10 mg/ml PF. In all groups, there were profound decreases, often to zero, in motion parameters with addition of 20 mg/ml PF. Thes e data indicated that 2.5 mg/ml PF may be the maximum beneficial conce ntration for normal sperm (i.e., fertile donors). PF appears to have a variable effect on subfertile sperm that may be related to initial sp erm quality. There were minimal effects on PT sperm. At concentrations >5 mg/ml, PF may have detrimental effects, reaching an obvious toxic level at 20 mg/ml.