title: Differential responses of human sperm to varying concentrations of pentoxyfylline with demonstration of toxicity.
abstract: Pentoxyfylline (PF), a methylxanthine derivative, is an inhibitor of the cAMP-phosphodiesterase enzyme, and is known to stimulate the motility of fresh and post-thaw human sperm. The purpose of this study was to examine the effects of different concentrations of PF on motility (MOT), path (curvilinear) velocity (PV), and hyperactivation (HA) of fresh sperm from patients (n = 24) and donors (n = 6) and post-thaw donor sperm (n = 5). For cryopreservation, the donor semen was frozen in liquid nitrogen using test-yolk-glycerol cryopreservative, stored for a minimum of 48 hours, then thawed at room temperature prior to assay. Aliquots of all samples to equal 10 x 10(6)/ml were diluted in 1 ml of the following: medium (human tubal fluid) only (control), or 2.5, 5, 10, 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: group 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 sperm, 2.5 mg/ml PF significantly stimulated PV and HA at 0, 1, and 2 hours, and MOT at 0, 0.5, and 2 hours. PF at 5 mg/ml resulted in a decreased PV and HA, whereas MOT was decreased by 10 mg/ml. In the < 20% MOT group, 2.5 mg/ml PF significantly stimulated MOT at 0.5, 1, and 2 hours, and HA at 0 and 2 hours. There was no effect on PV.(ABSTRACT TRUNCATED AT 250 WORDS)
authors.affiliation: Department of Obstetrics and Gynecology, University of Rochester Medical Center, New York, USA.
authors.forename: G M
authors.initials: GM
authors.lastname: Centola
authors.forename: R J
authors.initials: RJ
authors.lastname: Cartie
authors.forename: C
authors.initials: C
authors.lastname: Cox
mesh_terms: D000704:Analysis of Variance; D004305:Dose-Response Relationship, Drug; D005307:Fertilization in Vitro; D006801:Humans; D008297:Male; D010431:Pentoxifylline / Q000008:administration & dosage / Q000633:toxicity*; D010726:Phosphodiesterase Inhibitors / Q000008:administration & dosage / Q000633:toxicity*; D013081:Sperm Motility / Q000187:drug effects; D013094:Spermatozoa / Q000187:drug effects*
chemical_list: D010726:Phosphodiesterase Inhibitors; D010431:Pentoxifylline