Fan Shutong, Zhao Yuhan, Pan Zhiwei, Gao Zhiqin, Liang Zumu, Pan Zhifang, Feng Weiguo
College of Bioscience and Technology, Weifang Medical University, Weifang, China.
College of Public Health and Management, Weifang Medical University, Weifang, China.
J Pept Sci. 2018 Oct;24(10):e3121. doi: 10.1002/psc.3121. Epub 2018 Sep 17.
Zinc finger protein 185 (ZNF185) belongs to the ZNF family and is involved in male reproduction. However, it is unclear whether ZNF185 may be a target candidate for contraceptive vaccines. In this study, antigenic peptides derived from ZNF185 were prepared, and their immune contraceptive effects were investigated using mice. Results from enzyme-linked immunosorbent assay (ELISAs) showed that peptide immunization induced an antibody titre increase that reached a peak in week 12. Peptide-3 and peptide-4 were then chosen for subsequent experiments. The results of the fertility assays showed that peptide immunization inhibited the mating and fertility rates of the mice, whereas there were no obvious changes in the number of pups per litter. Subsequently, epididymal sperm was analysed. The results demonstrated that the sperm count and sperm motility were significantly decreased in the peptide group, while the amount of abnormal sperm was significantly increased in the peptide-3 group. The male reproductive organs were also evaluated. There were no obvious differences in testis or epididymal weights, in the diameters of the seminiferous tubules, or in the thicknesses of the seminiferous epithelium between the peptide group and the phosphate buffer saline (PBS) group. In addition, histological analysis indicated that there were no obvious pathologic changes in testis and epididymal histology in the peptide group; however, the number of spermatozoa present in the epididymal lumen of the peptide group was significantly decreased when compared with the PBS group. Our study demonstrates for the first time that peptides derived from ZNF185 may induce fertility suppression in mice without damaging reproductive organs. These peptides have the potential to be used as a male contraceptive vaccine.
锌指蛋白185(ZNF185)属于锌指蛋白家族,参与雄性生殖过程。然而,ZNF185是否可能成为避孕疫苗的候选靶点尚不清楚。在本研究中,制备了源自ZNF185的抗原肽,并使用小鼠研究了它们的免疫避孕效果。酶联免疫吸附测定(ELISA)结果显示,肽免疫诱导抗体滴度升高,在第12周达到峰值。然后选择肽-3和肽-4进行后续实验。生育力测定结果表明,肽免疫抑制了小鼠的交配率和生育率,而每窝幼崽数量没有明显变化。随后,对附睾精子进行了分析。结果表明,肽组的精子数量和精子活力显著降低,而肽-3组的异常精子数量显著增加。还对雄性生殖器官进行了评估。肽组与磷酸盐缓冲盐水(PBS)组在睾丸或附睾重量、曲细精管直径或生精上皮厚度方面没有明显差异。此外,组织学分析表明,肽组的睾丸和附睾组织学没有明显病理变化;然而,与PBS组相比,肽组附睾管腔内的精子数量显著减少。我们的研究首次证明,源自ZNF185的肽可能在不损害生殖器官的情况下诱导小鼠生育力抑制。这些肽有潜力用作男性避孕疫苗。