Abstract
Human sperm have to undergo a maturational process called capacitation in the female reproductive tract. Capacitation confers upon the sperm an ability to gain hypermotility and undergo acrosome reaction. Previous studies have suggested that seminal plasma proteins induce the capacitation of sperm in the female reproductive tract for the successful fertilization of the oocyte. However, the function of seminal plasma proteins in capacitation remains largely unclear. To the end, we found that soluble CD38 (sCD38) in seminal plasma increases the capacitation of sperm via specific interactions between sCD38 and the CD31 on the sperm. Upon the association of sCD38 with CD31, tyrosine kinase Src phosphorylates CD31, a process blocked by Src inhibitors. Shc, SHP-2, Grb2, and SOS, as well as Src kinase were found to associate with the phosphorylated CD31. The sCD38-induced phosphorylation of CD31 initiates a cascade reaction through the phosphorylation of Erk1/2, which results in the acrosome reaction, and sperm hypermotility. These processes were prevented by Src, Ras and MEK inhibitors. Taken together, these data indicate that the sCD38 present in seminal plasma plays a critical role in the capacitation of sperm.
Highlights
Mammalian seminal plasma is a physiological secretion that originates from multiple glands in the male reproductive tract that plays an important role in the final maturation of the spermatozoa [1]
We showed that soluble CD38 (sCD38) is present in sufficient quantity in seminal plasma to induce tyrosine phosphorylation of the CD31 in cells and demonstrate that sCD38 has a positive effect on sperm capacitation, which plays an important role in fertility
An in-gel activity assay of CD38 showed two different molecular weight fluorescent bands (S1 Fig); the lower molecular weight form is soluble CD38 that originated from seminal vesicles, and the 45 kDa CD38 form is localized in the prostasomes as an intact form
Summary
Mammalian seminal plasma is a physiological secretion that originates from multiple glands in the male reproductive tract that plays an important role in the final maturation of the spermatozoa [1]. Capacitation confers upon the sperm an ability to gain hypermotility and undergo acrosomal reaction [2]. The intracellular signaling pathways implicated in capacitation that have been reported include an increase in membrane fluidity, cholesterol efflux, an increase in intracellular Ca2+ concentrations, and increased protein tyrosine phosphorylation [3]. Protein tyrosine phosphorylation is an essential aspect of capacitation [4]. It has been proposed that seminal plasma proteins, present in secretions from seminal vesicles and prostate glands, regulate the capacitation of sperm [5], the molecular mechanisms and signal transduction pathways involved in this process are not clearly understood.
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