Commonality and heterogeneity of pacemaker mechanisms in the male reproductive organs

Abstract

During emission, the first phase of ejaculation, smooth muscle in organs of the male reproductive tract (MRT) vigorously contract upon sympathetic nerve excitation to expel semen consisting of sperm and seminal plasma. During inter-ejaculation phases, the epididymis, seminal vesicles and prostate undergo spontaneous phasic contractions (SPCs), this transporting and maintaining the quality of sperm and seminal plasma. Recent studies have revealed platelet-derived growth factor receptor α-expressing (PDGFRα⁺) subepithelial interstitial cells in seminal vesicles subserve the role of pacemaker cells that electrically drive SPCs in this organ. PDGFRα⁺ smooth muscle cells in the epididymis also appear to function as pacemaker cells implicating PDGFRα as a potential signature molecule in MRT pacemaking. The dominant mechanism driving pacemaking in these organs is the cytosolic Ca²⁺ oscillator. This operates through entrainment of the release-refill cycle of Ca²⁺ stores, the released Ca²⁺ ions opening Ca²⁺-activated chloride channels, including in some cases ANO1 (TMEM16A), with the resultant pacemaker potential activating L-type voltage-dependent Ca²⁺ channels in the smooth muscle causing contraction (viz. SPCs). A second pacemaker mechanism, namely the membrane oscillator also has a role in specific cases. Further investigations into the commonality and heterogeneity of MRT pacemakers will open an avenue for understanding the pathogenesis of male infertility associated with deterioration of seminal plasma.