Immunization Against a Conserved Short 13-Amino Acid Receptor-Binding Epitope of FSHβ Reduces Spermatogenesis and Sperm Motility in Male Mice

Background: Follicle-stimulating hormone (FSH)-based vaccines show the potential to disrupt spermatogenesis without disturbing sexual function and libido in males. Herein, we developed a novel FSH vaccine based on the tandem of a conserved 13-amino acid receptor-binding epitope of FSHβ (FSHβ13AA-T) and tested its effect on reproductive physiology and function using the male mouse as a model. Methods: Serum reproductive hormone levels, testicular histology, daily sperm production, sperm motility, libido and fertility of male mice following FSH vaccination were determined. Results: Compared to placebo-immunized controls, FSH vaccination triggered (p < 0.05) marked antibody generation, inhibited spermatogenesis and reduced sperm motility (p < 0.05), without adverse effects on serum LH and testosterone levels as well as the libido of male mice. Mechanistically, FSH vaccination suppressed (p < 0.05) testicular local estrogen production by downregulated aromatase encoding gene Cyp19a1 expression and also downregulated (p < 0.05) expression of key spermatogenic genes in testes, including Creb, INHα, Wnt2, Aqp8, Cmtm2a and Spata19, thus disrupting and impairing spermatogenesis and sperm motility. Conclusions: These results demonstrate that immunization of male mice against FSHβ13AA could substantially inhibit spermatogenesis and reduce sperm motility. Thus, FSHβ13AA-based vaccines hold potential for development as male contraceptives that do not compromise libido in species including men in which FSH is essential for spermatogenesis.