Capacitation


A past project


At mating, mammalian sperm are unable to fertilize, even when placed in direct contact with an egg.  The inability of sperm to fertilize confounded scientists for many years, and hindered the study of fertilization.  It wasn’t until the 1950’s, when two scientists working independently, shed light on this problem.  M.C. Chang, found that when he added sperm into the oviducts of rabbits at various times relative to induced ovulation, that they fertilized at different rates.


 
Adapted from Chang, M.C. 1951. Nature 168: 697-8

Adapted from Chang, M.C. 1951. Nature 168: 697-8

 

Chang reported that in the rabbit, fertilization success varied with time of tubal insemination relative to time of induced ovulation.  Chang and another scientist named Austin, both found that sperm recovered after longer residence in the female-donor fertilized recipient females more quickly.  These findings suggested that sperm undergo physiological changes while residing in the female reproductive tract, and that these changes confer upon them the capacity to fertility.  Austin later coined the term capacitation to denote these physiologic changes (Austin, C.R. 1951. Aust. J. Sci B 4: 581-96).

I have a long-standing interest in elucidating the signaling pathways involved in sperm capacitation.  I focused on two events of capacitation.  Primarily, I studied the signaling events in mammalian sperm that occur within the first seconds after ejaculation when relatively immotile sperm initiate rapid swimming, a process termed activation.  I was also interested in another change in motility that occurs late in capacitation, hyperactivation, that may be required for sperm to complete fertilization.


Activation


Activation specifically refers to the more vigorous movement that occurs when sperm come into contact with the bicarbonate (the HCO3- anion) contained in male and/or female reproductive fluids.  At mating, sperm need to travel a large distance from the site of sperm deposition (typically the vagina or uterus) to the site of fertilization (oviducts).  Vigorous swimming in relatively linear trajectories may aid sperm in achieving this goal.  In physiological salt solutions in vitro, bicarbonate  is sufficient to produce this activation of vigorous motility.


Hyperactivation



Hyperactivation occurs near the site and time of fertilization.  Hyperactivated sperm are characterized as having a very asymmetric flagellar beat.  Whereas activated sperm swim in a relatively straight line, hyperactivated sperm swim with a circular path.

 
 These are a time series of actual traces made from the flagella of a hyperactivated sperm.  Notice that the asymmetry of the distal flagellum during this beat cycle (Carlson et al. 2003).

 These are a time series of actual traces made from the flagella of a hyperactivated sperm.  Notice that the asymmetry of the distal flagellum during this beat cycle (Carlson et al. 2003).

 

We have found that sperm from the CatSper-/- mice do not undergo hyperacitivation and do not display the asymmetric beat (see below) even after exposure to capacitating conditions known to produce hyperactivation in wild-type sperm.  


 
Another time series of traces made from the flagella of a CatSper-/- sperm (Carlson et al. 2003).

Another time series of traces made from the flagella of a CatSper-/- sperm (Carlson et al. 2003).