Muscarinic Acetylcholine Receptor Subtypes in the Male Reproductive Tract

Abstract

In mammals, at least five different muscarinic acetylcholine receptor subtypes (mAChRs; M(1)-M(5)) are known to be widely expressed and distributed in different tissues from different species. They mediate distinct physiological functions according to their location and receptor subtype. Multiple events are associated with the regulation of intracellular signaling by mAChRs, and a coordinated balance of the molecular mechanisms governing receptor signaling, desensitization, resensitization, and mitogenic signaling is known to occur in various cell types. Most of the actions of acetylcholine (ACh) in the male reproductive tract are induced by its effects on mAChRs, but the role of specific mAChR subtypes on male reproductive function and fertility are still not well understood. The rat efferent ductules and epididymis are androgen-dependent tissues of the male reproductive tract, with important roles in the process to form a viable and fertile sperm. In the present study, aspects of the expression, localization, and potential function of mAChR subtypes in rat efferent ductules and epididymis are reviewed. Furthermore, evidences for the implication of mAChRs in the regulation of protein synthesis and secretion in these tissues are presented. Taken together, the studies contribute to our understanding about physiological aspects of mAChR and mechanisms by which the cholinergic system affects male reproduction.

Members of the murine Pate family are predominantly expressed in the epididymis in a segment-specific fashion and regulated by androgens and other testicular factors

“…Most toxin proteins exert their function by regulating the activities of certain ion-channels, and hPATE-B, mPATE-C and mPATE-P have been shown to affect through nACHRs [17], and mPATE-B to regulate Ca 2+ transport [24]. Although the sperm acrosome reaction has been shown to be mediated through nAChRs [36], the majority of acetylcholine effects in spermatozoa is thought to be carried out by muscarinic AChRs [37], indicating that the PATE proteins may not interact with the spermatozoa directly. However, hPATE-B has been shown to bind to spermatozoa, and due to mediation of Ca 2+ transport, a role in regulation of the acrosome reaction has been suggested [24].…”

The Non-Neuronal Cholinergic System in Health and Disease

“…Many effects of ACh in the male reproductive tract such as vaso-activity, sperm transport, muscle contraction and cell secretion are mediated via mAChR [165]. However, more research in this area is needed to explore the exact functional influence of the NNCS and its possible role in reproductive system pathology.…”

Short- and long-term exposure to methamidophos impairs spermatogenesis in mice

“…Thus, a decrease in receptor density may be responsible for the weight increase observed in this study. Furthermore, downregulation may have occurred in the vas deferens musculature and hindered ejaculation, since mAChR are expressed in the vas deferens of rodents [26,27]. This event, in turn, may have promoted the accumulation of spermatozoa in the epididymides, resulting in the increased weight of this tissue observed after long-term exposure.…”

“…It is possible, therefore, that the sperm transit reduction in the caput/ corpus epididymis in MET-treated mice in the short-term exposure group is a result of excess ACh in mAChR. These receptors are expressed in different cell types in the epididymides of rodents and are involved in the modulation of smooth muscle contraction and epithelial cell activity [26,27]. Thus, hyperstimulation of the mAChR and cholinergic overload may have increased contractility and promoted the release of spermatozoa from the epididymis.…”