A novel dominant B-cell epitope of FSHR identified by molecular docking induced specific immune response and suppressed fertility

Abstract

The follicle stimulating hormone (FSH) is of great importance in reproduction modulation of both sexes. The extracellular domain (ECD) of its receptor (FSHR) is crucial for FSH binding and subsequent signal transduction; therefore, it is the potential target for fertility control. To avoid unwanted side-effect when used as immunocontraceptive agent, the ECD was analysed by online prediction combined with molecular docking to identify the candidate B-cell epitopes. Four potential B-cell epitopes were identified and synthesised in tandem with Pan DR epitope. Then the epitope-based peptides were used to boost adult male mice following rhFSHR protein priming, thus to determine their immune responses and fertility inhibition capacity. Three of the four peptides showed suppressed fertility accompanied with small testis and lower serum testosterone level, which was consistent with absolutely lower sperm quantity and poor quality. Among the four epitope peptides, Pep2 displayed the lowest fertility rate of 26.67%, which was similar to that of rhFSHR homologously prime/boost mice (23.30 and 25.00%). Thus, we identified a novel immunodominant B-cell epitope by molecular docking and protein prime/peptide boost strategy.

Keywords:

• Follicle stimulating hormone receptor
• extracellular domain
• molecular docking
• B-cell epitope
• contraception

Acknowledgements

Wei He and Ping Yan contributed equally to this work. We appreciate Prof. Yun Zhang for her kindness correcting English grammar errors of this manuscript. This research was funded by grants from National Key Technology Research and Development Program of China (Grant 2006BAI03B12) and National Natural Science Foundation of China (No.30571708 and 30490241).