Context: Endogenous opioid peptides signal through δ-, κ-, and μ-opioid receptors. Some of these peptides such as endorphins and enkephalins are present in the male reproductive tract, but the presence of the corresponding receptors in human sperm cells has not yet been reported. Objective: Our objective was to study the expression and localization of δ-, κ-, and μ-opioid receptors on human spermatozoa and the implication in sperm motility. Methods: The expression of receptors was studied by RT-PCR, Western blot, and immunofluorescence techniques. We evaluated the effects of activation of each opioid receptor by specific agonist and antagonist. Results: Human spermatozoa express δ-, κ-, and μ-opioid receptors. These receptors were located in different parts of the head, in the middle region, and in the tail of the sperm. Progressive motility of spermatozoa, an important parameter to evaluate male fertility, was found to be significantly reduced after incubation with the μ-receptor agonist morphine, whereas this effect was antagonized in the presence of the corresponding antagonist naloxone. The δ-receptor antagonist naltrindole significantly reduced progressive motility immediately after its addition. However, the δ-receptor agonist DPDPE had no significant effect. Finally, neither the κ-receptor agonist U50488 nor its antagonist nor-binaltorphimine significantly affected the progressive motility of human spermatozoa. Conclusion: We report for first time the presence of functional δ-, κ-, and μ-opioid receptors in human sperm membranes. These findings are indicative of a role for the opioid system in the regulation of sperm physiology.

Endogenous opioid peptides are substances involved in cell communication. They are present in various organs and tissues of the male and female reproductive tract, suggesting that they may regulate some of the processes involved in reproductive function. In fact, the opioid system that operates as a multi-messenger system can participate in the regulation of reproductive physiology at multiple levels, for example, at the levels of the central nervous system, at the testes level and at sperm level. A better understanding of the implication of the opioid system in reproductive processes may contribute to clarifying the etiology of many cases of infertility and the effect of opiate abuse on fertility. Indeed, a novel biochemical tool for the diagnosis and treatment of male infertility could be based upon components of the opioid system. The presence of the opioid system in sperm cells also represents a novel opportunity for reproductive management, for either enhancing the probability of fertilization or reducing it through the development of novel targeted contraceptives.

The renin-angiotensin system (RAS) is a peptidic system known mainly for its roles in the maintenance of blood pressure and electrolyte and fluid homeostasis. However, several tissues and cells have been described to possess an intrinsic RAS that acts locally through different paracrine and autocrine mechanisms. In the male reproductive system, several components of this system have been observed in various organs and tissues, such as the testes, spermatozoa and seminal fluid. Some functions attributed to this local RAS are maintenance of seminal plasma electrolytes, regulation of steroidogenesis and spermatogenesis, and sperm functions. However, their specific actions in these locations are not fully understood. Therefore, a deep knowledge of the functions of the RAS at both the testicular and seminal levels could clarify its roles in male infertility and sperm physiology, and the different RAS elements could be used to design tools enabling the diagnosis and/or treatment of male infertility.

During the last seventy years, studies on mammalian sperm cells have demonstrated the essential role of capacitation, hyperactivation and the acrosome reaction in the acquisition of fertilization ability. These studies revealed the important biochemical and physiological changes that sperm undergo in their travel throughout the female genital tract, including changes in membrane fluidity, the activation of soluble adenylate cyclase, increases in intracellular pH and Ca²⁺ and the development of motility. Sperm are highly polarized cells, with a resting membrane potential of about −40 mV, which must rapidly adapt to the ionic changes occurring through the sperm membrane. This review summarizes the current knowledge about the relationship between variations in the sperm potential membrane, including depolarization and hyperpolarization, and their correlation with changes in sperm motility and capacitation to further lead to the acrosome reaction, a calcium-dependent exocytosis process. We also review the functionality of different ion channels that are present in spermatozoa in order to understand their association with human infertility.