Reproduction Abstracts

Introduction: SPRASA is a protein, that is expressed in the acrosome of sperm, as wel as on the oolemma of many mammals, which we identified as the target of antisperm antibodies from some infertile men. In order to further understand the importance of SPRASA we produced knockout mice and examined the effect of this gene knockout on murine fertility.

Methods: With ethics approval (AEC_R811) knockout mice were generated lacking the expression of exons 4 and 5 of the SPACA-3 gene that encodes SPRASA, and a breeding colony established. Sperm extracted from the distal vas deferens or cauda epididymis of eight week (n=5) and eight month (n=4) old knockout or control males was counted and graded for motility. Right ovaries from control (n=4) or SPRASA knockout (n=4) females were sectioned and the number of follicles at each stage counted. Homozygous SPRASA knockout (n=16) or control (n=7) breeding pairs were monitored for litter size and time between litters.

Results: There were no significant differences in sperm count or motility between SPRASA knockout or controls (P>0.05) at eight weeks or eight months age. There was no significant difference in the number of follicles, at any stage of development, between control and SPRASA knockout females (P<0.05). Litter size was significantly (P,0.0001) smaller in SRPASA knockout (five pups) than control (seven pups) controls. Average time between litters was significantly (P=0.0076) longer in SPRASA knockout (32.4 days) than control mice (24.5 days).

Discussion: Our observations of mice genetically deficient in SPRASA suggest that deletion of SPRASA does not affect production of either sperm or oocytes but does reduce fertility. This result supports existing evidence from in vitro models showing that SPRASA is involved in sperm-oocyte interactions and confirms that SPRASA is potentially a useful target for the control of fertility.