• PMID: 14657366
• Gene Name: CATSPER2
• Condition: Infertility
• Association: The study concludes that CatSper2 is responsible for driving hyperactivated motility which is necessary for fertilization
• Sex: Male
• Infertility type: Male infertility

Hyperactivated sperm motility driven by CatSper2 is required for fertilization

Quill TA, Sugden SA, Rossi KL, Doolittle LK, Hammer RE, Garbers DL.

Elevations of sperm Ca2+ seem to be responsible for an asymmetric form of motility called hyperactivation, which is first seen near the time of fertilization. The mechanism by which intracellular Ca2+ concentrations increase remains unknown despite considerable investigation. Although several prototypical voltage-gated calcium channels are present in spermatozoa, they are not essential for motility. Furthermore, the forward velocity and percentage of motility of spermatozoa are associated with infertility, but their importance relative to hyperactivation also remains unknown. We show here that disruption of the gene for a recently described sperm-specific voltage-gated cation channel, CatSper2, fails to significantly alter sperm production, protein tyrosine phosphorylation that is associated with capacitation, induction of the acrosome reaction, forward velocity, or percentage of motility, yet CatSper2-/- males are completely infertile. The defect that we identify in the null sperm cells is a failure to acquire hyperactivated motility, which seems to render spermatozoa incapable of generating the "power" needed for penetration of the extracellular matrix of the egg. A loss of power is suggested also by experiments in which the viscosity of the medium was increased after incubation of spermatozoa in normal capacitating conditions. In high-viscosity medium, CatSper2-null spermatozoa lost the ability to swim forward, whereas wild-type cells continued to move forward. Thus, CatSper2 is responsible for driving hyperactivated motility, and, even with typical sperm forward velocities, fertilization is not possible in the absence of this highly active form of motility. FAU - Quill, Timothy A AU - Quill TA AD - Cecil H. and Ida Green Center for Reproductive Biology Sciences, Howard Hughes Medical Institute and Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75390-9051, USA. FAU - Sugden, Sarah A AU - Sugden SA FAU - Rossi, Kristen L AU - Rossi KL FAU - Doolittle, Lynda K AU - Doolittle LK FAU - Hammer, Robert E AU - Hammer RE