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

Seghatoleslam, Atefeh and Ferro, Valerie and Mansourian, Maryam and Kargar, Maryam and Hosseini, Mohammad Hossein and Manavian, Mohsen and Gebril, Ayman M and Mostavi-Pour, Zohre and Namavari, Mehdi (2013) Evaluation of immunocastration conjugates based on GnRH linked to carrier molecules in a male rodent model. Comparative Clinical Pathology.

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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.