Correlation between intracellular cAMP content, kinematic parameters and hyperactivation of human spermatozoa after incubation with pentoxifylline

Abstract

Various compounds have been used in the attempt to improve sperm motility, including pentoxifylline (PF), a methylxanthine derivative. It has been postulated that PF, being a phosphodiesterase inhibitor, increases sperm kinematic parameters and the number of spermatozoa exhibiting hyperactivated motility by raising the intracellular content of cAMP, a molecule involved in the generation of sperm energy. However, it has not been clarified whether the biological effects of PF on sperm motility correlate with its ability to increase intracellular cAMP levels. To examine this relationship, the kinematic parameters, hyperactivation, and intracellular cAMP content were evaluated in motile spermatozoa, obtained by discontinuous Percoll gradient and swim-up from 21 normozoospermic semen samples, incubated without and with PF for 0, 1, 2, and 4 h. PF increased beat cross frequency after 1 and 2 h of incubation, curvilinear velocity and lateral head displacement (ALH) after 4 h, and hyperactivation after 1, 2, and 4 h, and decreased linearity (LIN) after 1 h of incubation. The intracellular cAMP content of spermatozoa incubated with PF increased at all time-points examined. Both intracellular cAMP content and increase in hyperactivation in response to PF decreased with the length of incubation. In the absence of PF, cAMP content was unchanged and was correlated significantly only with ALH and the percentage of spermatozoa with hyperactivated motility. Following incubation with PF, cAMP content correlated with hyperactivation and all sperm kinematic parameters, with the exception of LIN and straightness. These findings suggest that the beneficial effects of PF on sperm kinematic parameters and hyperactivation are related to its ability to increase intracellular cAMP content.

Chorionic morphine, naltrexone and pentoxifylline effect on hypophyso-gonadal hormones of male rats

“…The stimulatory effect of pentoxifylline on sperm parameters can clearly be attributed to the increased intracellular levels of cAMP (23). Cyclic AMP, in turn, is believed to stimulate the cAMP-dependent kinase (24), which itself induces sperm tail protein phosphorylation (25) with subsequent increase in sperm motility (26).…”

Glycodelin-S in Human Seminal Plasma Reduces Cholesterol Efflux andInhibits Capacitation ofSpermatozoa

“…Determination of cAMP-Intracellular cAMP was extracted as described by Calogero and coworkers (27). Briefly, spermatozoa that had been incubated for various durations were collected by centrifugation at 3,000 ϫ g for 5 min, and resuspended in 0.5 ml of ice-cold 90% ethanol.…”

Efeitos da pentoxifilina sobre a qualidade espermática e hemodinâmica uterina em equinos

“…Sendo assim, a pentoxifilina vem sendo estudada quanto a sua atuação no incremento da motilidade espermática (CALOGERO et al, 1998) assim como na vascularização de tecidos, devido propriedades reológicas e imunomoduladoras (WARD;CLISSOLD, 1987).…”

“…A pentoxifilina é conhecida por estimular a motilidade de sêmen humano fresco e criopreservado (CENTOLA; CARTIE; COX, 1995), ela melhora as características cinéticas e o número de espermatozoides exibindo motilidade hiperativada (CALOGERO et al, 1998). …”

“…Esta substância inibe a enzima fosfodiesterase, aumentando a concentração de AMPc (adenosina monofosfato cíclico) no interior das células. Desta forma, a geração de energia que atua diretamente no controle flagelar do espermatozoide é mantida, melhorando assim a motilidade dos espermatozoides (CALOGERO et al, 1998, SHEN et al, 1991, GRADIL & BALL, 2000, MARQUES et al, 2002.…”