Human sperm responses to calcitonin, angiotensin II and fertilization-promoting peptide in prepared semen samples from normal donors and infertility patients

Background: Fertilization-promoting peptide (FPP), angiotensin II (AII) and calcitonin, present in seminal plasma, have significant effects on mouse sperm function in vitro. This study investigated responses of uncapacitated and capacitated human sperm to these peptides, initially using samples from donors with normal semen parameters and then samples from men attending infertility clinics. Methods: Prepared suspensions were incubated in the presence/absence of a range of peptide concentrations and assessed using chlortetracycline (CTC) analysis and the hamster oocyte penetration test. Results: In uncapacitated suspensions, maximal stimulatory responses (CTC) were obtained with calcitonin at 0.5-15 nmol/l and AII at 0.3-100 nmol/l; FPP is known to be most effective at 100 nmol/l. All peptides also significantly stimulated sperm penetrating ability. Combinations of peptides at low concentrations, having no detectable effect when used singly, elicited significant responses, suggesting that they work via the same signalling pathway. In suspensions incubated in the presence of fucose to accelerate capacitation and acrosome reactions, both FPP and calcitonin, but not AII, inhibited acrosome loss; however, AII did not interfere with responses to FPP and calcitonin. Unlike samples from 15 donors, some samples from >70 patients had high proportions of capacitated and/or acrosome-reacted cells when assessed immediately following preparation. Even so, the peptides usually elicited responses similar to those obtained with donor samples and combinations of peptides inhibited spontaneous acrosome loss for at least 3 h. Conclusions: The responses obtained in vitro suggest that these peptides could have significant effects on human sperm function in vivo and could also be used effectively in infertility clinics.