Construction of a Catsper1 DNA Vaccine and Its Antifertility Effect on Male Mice

Abstract

Cation channel of sperm 1 (CATSPER1) is a unique sperm cation channel protein, and essential for sperm function and male fertility. CATSPER1 exclusively expresses in meiotic and postmeiotic spermatogenic cells, thus belongs to the spermatogenesis-specific antigen that escape central tolerance. We have previously demonstrated the immunocontraceptive potential of its transmembrane domains and pore region, and reported the antifertility effects of its B-cell epitopes on male mice. Aiming to develop DNA vaccine targeting CATSPER1 for male contraception, here the whole open reading frame of mouse Catsper1 was cloned into the plasmid pEGFP-N1 to obtain a DNA vaccine pEGFP-N1-Catsper1. The vaccine was confirmed to be transcribed and translated in mouse N2a cell in vitro and mouse muscle tissue in vivo. Intramuscular injection with the vaccine on male mice induced specific immune reaction and caused significant inhibition on sperm hyperactivated motility and progressive motility (P<0.001 for both), and consequently reduced male fertility. The fertility rate of experimental group was 40.9%, which was significant lower (P=0.012) than control group (81.8%). No significant change in mating behavior, sperm production and histology of testis/epididymis was observed. Given that Catsper1 exhibits a high degree of homology among different species, Catsper1 DNA vaccine might be a good strategy for developing an immunocontraceptive vaccine for human and animal use.

ZNF185‐derived peptide induces fertility suppression in mice

“…Previous studies have reported an apparent decrease in testis and epididymal weights, as well as obvious pathologic changes in the seminiferous tubules, of immunization animals . However, other studies have shown no pathological changes in the testis and epididymis . Our study was consistent with the latter.…”

“…The fertility assays revealed that the mating fertility rates of the peptide group decreased significantly compared with the PBS group. The mechanism facilitating this decrease in fertility may be that peptides derived from ZNF185 induce specific antibody increases, which then enter the male reproductive tract through the serum and further suppress ZNF185 function . These results also validated our previous study, which indicated that ZNF185 is involved in spermatogenesis and male reproduction .…”

“…The mechanism facilitating this decrease in fertility may be that peptides derived from ZNF185 induce specific antibody increases, which then enter the male reproductive tract through the serum and further suppress ZNF185 function. 1,25 These results also validated our previous study, which indicated that ZNF185 is involved in spermatogenesis and male reproduction. 8 However, the antifertility effects of ZNF185, including mating rate (58.3%) and fertility rate (25.0%), were far too low to be used as an efficient contraceptive vaccine.…”

“…However, antibody titres from the other peptides were lower than those in the peptide‐3 group. This difference may be due to different immune potentials of the individual peptides . After considering the effects of the different antibody titres on fertility, peptide‐3 and peptide‐4 were chosen for subsequent experiments.…”

“…Despite a broad availability of various contraceptives, the world's population is growing at a tremendous rate and is projected to reach 8 billion by 2020. 1 At present, the available contraceptive choices for men are limited to condoms and vasectomies, 2 which have the potential to adversely affect the health of individual users. There is an urgent need for a male contraception method that is highly effective, safe, reversible, inexpensive, and easily accessible.…”