TCP-11, the product of a mouset-complex gene, plays a role in stimulation of capacitation and inhibition of the spontaneous acrosome reaction

Abstract

Tcp‐11 is a candidate for a distorter gene within the t‐complex on mouse chromosome 17; although t‐complex genes appear to affect sperm function, relatively little is known about mechanisms whereby these genes might play a specific physiological role. We present evidence that the protein TCP‐11 is found on the surface of mature epididymal spermatozoa. Although detected on both the acrosomal cap region of the head and the flagellum of acrosome‐intact cells, it is absent from the heads of acrosome‐reacted cells. When epididymal spermatozoa were incubated in the presence of anti‐TCP‐11 IgG Fab fragments for a total of 120 min and assessed using chlortetracycline fluorescence, we observed a stimulation of capacitation and an inhibition of spontaneous acrosome loss, suggestive of enhanced fertility compared with untreated suspensions. In vitro fertilization experiments confirmed that Fab‐treated suspensions became fertile more quickly and then maintained high fertility. Because these responses were remarkably similar to those obtained using the TRH‐related peptide FPP (fertilization promoting peptide; pGlu‐Glu‐ProNH2) and adenosine, we investigated responses to Fab fragments, FPP, and adenosine. Results indicated that the Fab fragments appear to work at the same extracellular site as FPP, one that is distinct from the adenosine site of action. Further evidence for this conclusion was obtained using pGlu‐Gln‐ProNH2, an FPP‐related tripeptide known to competitively inhibit responses to FPP; as with FPP, pGlu‐Gln‐ProNH2 inhibited the stimulatory effect of Fab fragments in a concentration‐dependent manner. From these results we suggest that TCP‐11 may be the receptor for FPP and that the adenylate clyclase/cyclic AMP pathway may be the signal transduction pathway activated by interactions between extracellular effector molecules (e.g., Fab fragments or FPP acting as an agonist) and TCP‐11. A mechanism such as this that promotes capacitation but inhibits spontaneous acrosome loss in vivo would play a very important role by helping to maximize the fertilizing potential of the few spermatozoa that reach the site of fertilization. The fact that there is a human homolog of Tcp‐11 suggests that this gene could play an important role in regulation of human, as well as mouse, sperm function. Mol. Reprod. Dev. 48:375–382, 1997. © 1997 Wiley‐Liss, Inc.

Modulation of the Function of Boar Spermatozoa via Adenosine and Fertilization Promoting Peptide Receptors Reduce the Incidence of Polyspermic Penetration into Porcine Oocytes1

“…However, not only in mouse [23] and human [33] spermatozoa but also in boar spermatozoa [2], FPP, as well as adenosine, has been shown to stimulate capacitation but to inhibit acrosome reaction. Recently, a putative FPP receptor, the protein TCP-11 coded by a t-complex gene, was identified in mouse spermatozoa [16].…”

“…In mice, not only adenosine but also fertilization-promoting peptide (pGlu-Glu-ProNH 2 ) has been shown to promote sperm capacitation and to inhibit spontaneous acrosome loss via separate and specific receptors to modulate the adenylyl cyclase/cAMP pathway [12,13]. Mouse spermatozoa have inhibitory (A1) and stimulatory (A2) adenosine receptors (AdRs) [14,15] and a putative FPP receptor [16]. In our recent study [2], both adenosine and FPP simulated capacitation but inhibited the acrosome reaction in a caffeine-free fertilization medium.…”

First Messenger Regulation of Mammalian Sperm Function via Adenylyl Cyclase/cAMP

“…TCP11 has been localized to the acrosomal cap region and to the flagellum, particularly to the principal piece [8], making it plausible that TCP11 and adenosine receptors could interact as proposed. Interestingly, antibodies directed against the stimulatory A2A and inhibitory A 1 adenosine receptors showed different staining patterns, depending on the capacitation state of the spermatozoa being evaluated (Fig.…”

Human t-Complex Protein 11 (TCP11), a Testis-Specific Gene Product, Is a Potential Determinant of the Sperm Morphology

“…It is only expressed during male germ cell development and found in mouse sperm, particularly in acrosome and flagellum (Fraser et al 1997).…”

“…The mouse Tcp11 gene encodes the receptor for fertilization-promoting peptide (FPP) and plays a role in stimulation of capacitation and inhibition of the spontaneous acrosome reaction (Fraser et al 1997). Human TCP11 is the homologous gene of mouse Tcp11 and is mapped to human chromosome band 6p21 (Ma et al 2002).…”