TCP-11, THE PRODUCT OF A MOUSE T-COMPLEX GENE, PLAYS A ROLE IN STIMULATION OF CAPACITATION AND INHIBITION OF THE SPONTANEOUS ACROSOME REACTION

Tcp-11 is a candidate for a distorter gene within the t-complex on mou se chromosome 17; although t-complex genes appear to affect sperm func tion, 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 spermatoz oa. Although detected on both the acrosomal cap region of the head and the flagellum of acrosome-intact cells, it is absent from the heads o f acrosome-reacted cells. When epididymal spermatozoa were incubated i n the presence of anti-TCP-ll IgG Fab fragments for a total of 120 min and assessed using chlortetracycline fluorescence, we observed a stim ulation 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 suspen sions became fertile move quickly and then maintained high fertility. Because these responses were remarkably similar to those obtained usin g the TRH-related peptide FPP (fertilization promoting peptide; pGlu-G lu-ProNH(2)) 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 fr om the adenosine site of action. Further evidence for this conclusion was obtained using pGlu-Gln-ProNH(2), an FPP-related tripeptide known to competitively inhibit responses to FPP; as with FPP, pGlu-Gln-ProNH (2), inhibited the stimulatory effect of Fab fragments in a concentrat ion-dependent manner. From these results we suggest that TCP-11 may be the receptor for FPP and that the adenylate clyclase/cyclic AMP pathw ay may be the signal transduction pathway activated by interactions be tween extracellular effector molecules (e.g., Fab fragments or FPP act ing 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 potentia l of the few spermatozoa that reach the site of fertilization. The fac t that there is a human homolog of Tcp-ll suggests that this gene coul d play an important role in regulation of human, as well as mouse, spe rm function. (C) 1997 Wiley-Liss, Inc.