Neurotensin stimulates the sperm acrosome reaction and reduces percentages of fertilization in vitro

Abstract

Objective To determine the impact of neurotensin (NTS), a naturally occurring peptide, on the function of human and nonhuman primate sperm. Design Experimental study. Setting University-based research laboratory. Patient(s)/Animal(s) Consenting normozoospermic human donors and cynomolgus macaques. Intervention(s) None. Main Outcome Measure(s) Sperm acrosome status was assessed. Computer-assisted semen analysis assessed sperm motility, progression, and velocity. Immunocytochemistry and receptor selective agonists were used to identify specific NTS receptors on sperm. Monkey oocytes were obtained after ovarian stimulation, and NTS-treated monkey sperm were used for in\xa0vitro fertilization. Results Neurotensin treatment of human sperm stimulated the acrosome reaction in both a dose-dependent (0.1–10 μmol/L) and time-dependent (5–30 minutes) manner. Neurotensin treatment did not alter sperm motility or progression. Both a general NTS receptor antagonist (SR142948) and a NTSR1 selective antagonist (SR48692) reduced the ability of NTS to stimulate the acrosome reaction. The neurotensin receptor NTSR1, but not NTSR2 or SORT1, was detected in monkey sperm using immunostaining. Neurotensin treatment also compromised the ability of sperm to fertilize an oocyte. Percentage of fertilization with untreated monkey sperm and monkey oocytes was 72%. Sperm pre-treated with NTS yielded a significantly lower fertilization rate of 18%. Conclusion(s) Neurotensin effectively stimulates the acrosome reaction in human and monkey sperm. Neurotensin produced by the oviduct or cumulus cells may promote natural fertilization. Pretreatment of sperm with NTS significantly reduces fertilization. Exposure of sperm to NTS prior to reaching the oviduct has the potential for contraceptive development. Identification of NTSR1 as the mediator of NTS action provides a specific target for future studies.