Evaluation of immunocastration conjugates based on GnRH linked to carrier molecules in a male rodent model

Atefeh Seghatoleslam, Valerie Ferro, Maryam Mansourian, Maryam Kargar, Mohammad Hossein Hosseini, Mohsen Manavian, Ayman M Gebril, Zohre Mostavi-Pour, Mehdi Namavari

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Gonadotropin-releasing hormone (GnRH) stimulates
the pituitary gland to secrete sex hormones. In the present
study, we evaluated different conjugates of GnRH to abrogate
sex hormone secretion in a male rat model. Firstly, GnRH-I
was conjugated to keyhole limpet haemocyanin (KLH) using
either whole-sequence GnRH-I or an analogue of GnRH-I
(CHWSYGLRPG-NH2) using glutaraldehyde cross linkage.
Six-week-old Sprague-Dawley male rats (n=6) were immunized
intramuscularly with the conjugates adsorbed onto alum,
equivalent to 50 μg of GnRH peptide and administered in
weeks 1, 3, 5 and 7. The study was concluded in week 15.
Comparison was made with untreated controls and previously
established anti-fertility conjugates: CHWSYGLRPG-NH2
(GnRH-I) or CHWSHDWKPG-NH2 (analogue of lamprey
GnRH-III, lGnRH-III) linked to tetanus toxoid (using a heterobifunctional
reagent to achieve cross linkage). Antibody
production, hormone levels and testicular diameter changes
were assessed, together with, sperm movement and effects on
organ weights. Similar high levels of antibody secretion were
observed in all the immunized groups, although whole GnRHI-
KLH produced a sustained level of production for an additional
week. Similarly, testosterone levels were significantly
(p<0.05) reduced in all immunized groups. There were no
significant changes observed in body weight and testicular
diameter of immunized animals compared with the untreated
controls. However, in terms of sperm motility and sperm
number, the best anti-fertility effects were observed with
lGnRH-III-TT and GnRH-I-KLH and to a lesser extent whole
GnRH-I-KLH. These groups also showed significant increase
in kidney weight. Finally, considering all the above-mentioned
subjects in addition to availability and easier and cheaper way
of preparation,we came to this conclusion that whole GnRH-IKLH
satisfactorily met most of our favourite criteria and could
be used in immunocastration vaccine production purposes
successfully.
Original languageEnglish
Number of pages7
JournalComparative Clinical Pathology
Early online date6 Feb 2013
DOIs
Publication statusPublished - Feb 2013

Keywords

  • evaluation
  • immunocastration conjugates
  • GnRH linked
  • carrier molecules
  • rodent model
  • male

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