Effects of Pituitary Adenylate Cyclase Activating Polypeptide on Human Sperm Motility

Abstract

Pituitary adenylate cyclase activating polypeptide (PACAP), a neuropeptide with diverse effects, was originally isolated as a hypothalamo-hypophyseal peptide. Subsequent studies showed highest levels of PACAP in the testis after the brain, suggesting that it influences the development and functioning of spermatozoa. Indeed, it has been proven that PACAP has an effect on spermatogenesis, both locally and via influencing the hypothalamo-hypophyseal-gonadal axis. The aim of the present study was to determine whether PACAP has an effect on human sperm motility and whether it is present in the human seminal fluid. Furthermore, the sperm head morphology was studied in mice lacking endogenous PACAP. Human samples were obtained from healthy adult volunteers and andrological patients. The effects of PACAP on the motility of human sperm cells were investigated using a computer aided sperm analysis system. In cases where the motility was lower, addition of PACAP to the samples increased the motility and the ratio of rapid progressive and medium progressive sperm motility groups. The presence of PACAP could not be detected in human seminal fluid samples by means of mass spectrometry. Investigating sperm head morphology with routine histology in PACAP deficient mice revealed that both the longitudinal and transverse diameters were significantly lower in PACAP deficient mice, without marked difference in the shape, as revealed by scanning electron microscopy.

Occurrence and Functions of PACAP in the Placenta

“…The findings with RIA also confirmed these increasing levels in late placentas compared to early placentas [4].…”

“…The reason for this is not elucidated yet, several mechanisms may be responsible for this effect. For example, PACAP is involved in spermatogenesis and sperm motility [4], in steroid hormone synthesis, in ovarian folliculogenesis, and in reproductive behavior [34,35]. The small litter can also be due to the premature intrauterine death and early postnatal death due to defects in breathing and temperature regulation [66,67].…”

“…This drew the attention to the peptide as a regulator of male fertility and reproduction. Indeed, PACAP was found to influence spermatogenesis at various levels [3][4][5][6].…”

Role of PACAP and VIP Signalling in Regulation of Chondrogenesis and Osteogenesis

“…Although the analysis of the genetically modifi ed animals has not been completed yet, our initial observations suggested alterations in the composition of the cartilage extracellular matrix and in the expression of various signalling molecules in the knee joints of PACAP KO mice (our unpublished data). In the reproductory system of these mice, the lack of PACAP gene resulted in reduced fertility and altered mating behavior of females [ 52 ], moreover the maturation [ 53 ] and the morphology [ 54 ] of gonadal cells showed notable differences. Further evidences support the idea of the regulation effect of PACAP on differentiation of various cells, as 2+ concentration leading to increased PP2B, PKC, or MAPK signalling activity.…”

Examination of PACAP-Like Immunoreactivity in Urogenital Tumor Samples

“…PACAP exerts an important role in the regulation of bladder innervation, sensory neuronal pathway of micturition reflex, and renin secretion in the kidney (Hautmann et al 2007;Yoshiyama and de Groat 2008;Arms and Vizzard 2011). In the peripheral organs, the highest concentration of PACAP can be measured in the testis, implying an important function in the regulation of spermatogenesis and testicular aging (Arimura et al 1991;Li and Arimura 2003;Lacombe et al 2006;Brubel et al 2012).…”