Modulation of Ovarian Function in Female Dogs Immunized with Bovine Luteinizing Hormone Receptor

Abstract

Adult female dogs were immunized with 0.5 mg bovine luteinizing hormone receptor (LH-R) encapsulated in a silastic subdermal implant and subsequently with four intramuscular booster injections of 0.1 mg LH-R each. Circulating LH-R antibody was detected in the sera 3 weeks post-implant. The appearance of LH-R antibody was associated with a decline in the serum progesterone concentrations to a range of 0-0.5 ng/ml until day 365 in the immunized dogs in comparison with a range of 5-10 ng in the control animals, suggesting a lack of ovulation and corpus luteum function in immunized dogs. The immunized dogs did not show signs of 'standing heat' and failed to ovulate when induced by LH-RH challenge. Serum oestradiol levels, however, remained in the range of 30-40 pg/ml in both the immunized and the control dogs. With the decline in the antibody titres, the hormonal profile and vaginal cytology returned to a fertile state and the dogs exhibited signs of 'standing heat', as well as vaginal bleeding. Dogs immunized with LH-R did not show any serious metabolic, local or systemic adverse effects. The hypothalamic--pituitary gonadal axis remained intact as indicated by little difference in pituitary LH levels between control and immunized animals, and by the release of LH by LH-RH challenge. These studies demonstrate that active immunization of female dogs with LH-R could immunomodulate ovarian function to cause a reversible state of infertility. It may be postulated that, due to extensive interspecies homology, a recombinant LH receptor-based immunocontraceptive vaccine may also be effective in other vertebrates.

Suppression of Fertility in Adult Dogs

“…More recently, bitches vaccinated against bovine LH receptor had oestrous suppression for more than 11 months and decreased progesterone that lasted from approximately 6 months to 1.5 years (Saxena et al. ). In both studies, the effect of the vaccine was transitory and all animals returned to a normal physiologic reproductive status once the titres declined.…”

Ovarian remnant syndrome in small animals

“…Immunocontraception targeting LH and its receptor has been successful in domestic carnivores and may be an attractive alternative for the clinical management of ORS (SAXENA et al, 2002). Vaccination of the bitch and queen with a bovine LH receptor vaccine resulted in estrus suppression for up to 11 months, with return to normal physiologic reproductive state after the antibody titers declined (SAXENA et al, 2002, SABEUR et al, 2003.…”

“…Vaccination of the bitch and queen with a bovine LH receptor vaccine resulted in estrus suppression for up to 11 months, with return to normal physiologic reproductive state after the antibody titers declined (SAXENA et al, 2002, SABEUR et al, 2003. Further development of GnRH or gonadotropin vaccines has been hampered by the need of applying multiple boosters to ensure the production and maintenance of high antibody titers.…”

Current advances in antifertility vaccines for fertility control and noncontraceptive applications

“…Antifertility vaccines based on gonadotropinreleasing hormone (GnRH) have also reached early clinical trials, although not exclusively for human contraception, as they require androgen supplementation to maintain libido and secondary sex characteristics [19,20]. Other hormone-associated targets under consideration include, luteinizing hormone (LH) [21], sex steroids [22][23][24] and reproductive hormone receptors [25,26]. However, these are still at the laboratory bench stage.…”