Immunization against Kisspeptin-54 perturb hypothalamic-pituitary-testicular signaling pathway in ram lambs

Theriogenology. 2019 Feb:125:193-202. doi: 10.1016/j.theriogenology.2018.10.029. Epub 2018 Nov 6.

Abstract

Kisspeptin, a peptide product of KISS1 gene, recently identified as essential upstream gatekeeper in hypothalamic-pituitary-gonadal (HPG) axis. This study was designed to investigate the effect of immunization against kisspeptin-54 on hypothalamic-pituitary-testicular signaling pathway. A total of ten intact 56-days-old ram lambs were used and randomized into the treatment and control groups, which were, respectively immunized by kisspeptin-54 based vaccine and the empty plasmid via intramuscular route. We employed indirect enzyme-linked immunosorbent assay and quantitative real-time PCR to characterize the difference in serum kisspeptin, luteinizing hormone, testosterone hormone concentration and mRNA expression of reproductive-related genes in HPG axis across kisspeptin-54 immunized and control ram lambs. Serum kisspeptin, luteinizing hormone and testosterone concentration in the treatment group was lower (p < 0.05) than that of the control group. Compared with the control group, the mRNA expression of the hypothalamic androgen receptor (AR), KISS1, G protein-coupled receptor (GPR54) and gonadotropin-releasing hormone (GnRH) was altered in the immunized group (p < 0.05). Moreover, mRNA expression of pituitary luteinizing hormone beta (LHβ), follicle stimulating hormone beta (FSHβ), and GnRH receptor as well as, testicular LH receptor and FSH receptor, were remarkably lower (P < 0.05) in the treatment group. We concluded that immunization against kisspeptin-54 reduced serum kisspeptin levels thereby, the normal hypothalamic-pituitary-testicular signaling pathway disrupted. This data provides a great insight for the use of kisspeptin to regulate reproduction.

Keywords: Anti-kisspeptin antibody; Antifertility vaccine; KISS1; Kisspeptin-54; Ram; Signaling pathway.

Publication types

  • Clinical Trial, Veterinary

MeSH terms

  • Animals
  • Gene Expression Regulation / drug effects
  • Hypothalamo-Hypophyseal System / immunology
  • Hypothalamo-Hypophyseal System / physiology*
  • Immunization
  • Kisspeptins / immunology*
  • Luteinizing Hormone / blood
  • Male
  • Pituitary Gland / physiology*
  • Plasmids
  • Random Allocation
  • Recombinant Proteins / immunology
  • Sheep / physiology*
  • Signal Transduction / physiology*
  • Testosterone / blood

Substances

  • Kisspeptins
  • Recombinant Proteins
  • Testosterone
  • Luteinizing Hormone