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Medium-throughput Screening Assays for Assessment of Effects on Ca2+-Signaling and Acrosome Reaction in Human Sperm
Published on: March 1, 2019
Construction of a catsper1 DNA vaccine and its antifertility effect on male mice
Qiong Yu1, Xiao-Qin Mei1, Xiao-Fang Ding2
1Family Planning Research Institute/Center of Reproductive Medicine, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, China.
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.
Insights
A novel DNA vaccine targeting Cation channel of sperm 1 (CATSPER1) effectively reduced male mouse fertility by inhibiting sperm motility. This CATSPER1 DNA vaccine shows promise for immunocontraception in humans and animals.
Area of Science:
- Reproductive Biology
- Immunology
- Molecular Biology
Background:
- Cation channel of sperm 1 (CATSPER1) is crucial for sperm function and male fertility.
- CATSPER1 is a spermatogenesis-specific antigen, making it a potential target for immunocontraception.
- Previous studies indicated the immunocontraceptive potential of CATSPER1 domains and epitopes.
Purpose of the Study:
- To develop and evaluate a DNA vaccine targeting mouse Catsper1 for male contraception.
- To assess the vaccine's efficacy in inducing an immune response and reducing male fertility.
Main Methods:
- Cloned the full open reading frame of mouse Catsper1 into pEGFP-N1 plasmid to create the DNA vaccine pEGFP-N1-Catsper1.
- Confirmed vaccine transcription and translation in vitro (N2a cells) and in vivo (mouse muscle).
- Administered the vaccine via intramuscular injection to male mice and evaluated effects on fertility, sperm motility, and reproductive organ histology.
Main Results:
- The CATSPER1 DNA vaccine was successfully transcribed and translated.
- Vaccination induced a specific immune response, significantly inhibiting sperm hyperactivated and progressive motility (P<0.001).
- Male mice vaccinated with pEGFP-N1-Catsper1 showed a reduced fertility rate (40.9%) compared to controls (81.8%, P=0.012), without affecting mating behavior or testis histology.
Conclusions:
- The developed CATSPER1 DNA vaccine effectively reduces male fertility in mice by impairing sperm motility.
- No adverse effects on general reproductive parameters or organ histology were observed.
- High homology of Catsper1 across species suggests potential for a broadly applicable immunocontraceptive vaccine for humans and animals.

