Vol. 24, Issue 1: Fall 2016

Movement of Sperm Activated by Progesterone

Lloyd Tripp

About 11% of the reproductive-age population in the U.S. suffers from a disease affecting their reproductive system according to the Center for Disease Control and Prevention. Researchers continue to study the biomechanical pathways of the reproductive system in search of curing issues of fertility. One issue found in infertile males is the inability for sperm to travel within the vaginal canal and reach egg. In vitro fertilization (IVF) has been the primary alternative when couples encounter such issues. However, researchers are making headway as to the mechanisms affecting the motility—or ability to move –of sperm within the female reproductive system.

The National Institute of Health has funded researchers from UC Berkeley, UC San Francisco and Yale University School of Medicine to study the molecular mechanisms that activate sperm’s hypermobile state. Within the male reproductive tract, sperm starts off as an immotile cell pushed along by the tracts muscles. When in contact with progesterone, the sperm is activated and begins its journey to the egg. Not much is known about the molecular mechanisms that activate the sperm’s flagella- a screw-shaped tail that spins to propel the sperm. What is known is that the sperm’s flagella must consume calcium to become activate. Before a sperm can begin its hyper-active phase, calcium must be absorbed from the environment and enter the flagella of the cell. This tail-like appendage provides the core function of movement for the sperm much like the motor on a speedboat provides the momentum.

Through enzyme pathway isolation methods, CatSper was found to be the main activation enzyme that triggers calcium influx. Before the sperm could interact with the progesterone in a lab setting, researchers exposed the sperm to a chemical that inhibits a family of enzymes thought to be involved in the activation of the hyperactive state. Subsequently, CatSper was the candidate found to be involved in the activation of ion channels in the mechanism. To activate CatSper itself, a protein that is found on the outer membrane of the sperm cell known as ABHD2 must be bound by progesterone. Researchers found that upon isolating and inactive ABHD2, exposure to a modified progesterone molecule failed to activate the membrane protein - confirming that ABHD2 is the molecular target (or activating substrate) for progesterone.

With this study, further research can be conducted on the impact of certain enzyme deficiencies within the male reproductive system. More couples could get treatment for male infertility alternatively to IVF procedures. Other possibilities in research include a possible male birth control pill that only deactivates the ABHD2 protein, allowing couples to use both male and female contraceptive pills rather than solely condoms or female birth control.