Rethinking the relationship between hyperactivation and chemotaxis in mammalian sperm

Abstract

Hyperactivation, a motility pattern of mammalian sperm in the oviduct, is essential to fertilization. Hyperactivation helps sperm to swim effectively through oviductal mucus, to escape from the sperm reservoir, and to penetrate the cumulus matrix and zona pellucida of the oocyte. There is some evidence that mammalian sperm can undergo chemotaxis; however, the relationship of chemotaxis to hyperactivation is unknown. Ca(2+) signaling is involved in hyperactivation and implicated in chemotaxis as well. In vivo, sperm hyperactivate in the lower oviduct, far from the cumulus-oocyte complex and possibly beyond the influence of chemotactic gradients emanating from the oocyte or cumulus. Thus, sperm are likely to be hyperactivated before sensing chemotactic gradients. Chemotactic signals might modulate hyperactivation to direct sperm toward oocytes as they reach a region of influence. Ca(2+)-directed modulation of hyperactivation is a potential mechanism of this process.

FIG. 1.

“Turn-and-run” model in marine sperm chemotaxis. Sperm sense changes in chemoattractant concentrations (gray) by using asymmetrical bends to “turn.” The “run” phase follows, during which sperm swim up the chemoattractant gradient in a relatively straight trajectory propelled by symmetrical flagellar beating. The trajectory of repeated “turn and run” forms a helix with an axis directed toward the source of the attractant (white circle).

FIG. 2.

A transilluminated mouse oviduct. The ovary and bursa have been removed, but the coiling of the oviduct has been left in place. The size of mouse sperm (about 125 μm) is illustrated above the scale bar. The approximate location of the sperm reservoir is shown. In the sperm reservoir, the mucosal surface of the oviduct is thrown into transverse folds, creating pockets. These can be more clearly seen, as indicated by arrows, in the upper isthmus of the oviduct. To appreciate the size of the oocytes and cumulus in the ampulla, one oocyte has been covered by a solid black circle and the border of its cumulus indicated by a dotted line.

FIG. 3.

Flagellar beating patterns in mouse sperm. Activated (progressive) sperm show a symmetrical beating pattern, characterized by low amplitude pro-hook (A) and anti-hook (D) bends. Sperm hyperactivating under capacitating conditions show increased pro-hook bends (B), while the anti-hook bends remain unchanged (E). Sperm treated with thimerosal to release Ca²⁺ from internal stores show low-amplitude pro-hook bends (C) and high-amplitude anti-hook bends (F). Original magnification ×1250.

FIG. 4.

Transmission and scanning electron micrographs illustrate the close relationship of the redundant nuclear envelope (RNE) and mitochondria at the base of the flagellum. A) Transmission electron micrographs of the neck region of bull sperm. The nucleus is indicated by N. B) The asterisks indicate the mitochondria at the base of the flagellum. Note that they are unwound from the mitochondrial helix in the midpiece. Bars = 3 μm. Figure reprinted with permission [72].