Abstract :
[en] Various molecules including steroids, prostaglandins, peptides and glycoproteins are largely used in reproduction programs in domestic mammals. Treatments including pituitary gonadotrophins (Follitropin —FSH-, Lutropin —LH-, human menopausal Gonadotrophin —hMG-) and placental gonadotrophins (human Chorionic Gonadotrophin —hCG-, equine Chorionic Gonadotrophin —eCG- also called Pregnant mare serum gonadotrophin —PMSG-) are used for a long time to treat infertility or as a way to better control the reproductive cycles of cattle, horses, goats, sheep, dogs, pigs and more recently rabbits, monkeys and humans.
The literature concerning the administration of gonadotrophins in different species than source species reports data’s on active immunization and suggests that repeated administration of these hormones lead to induction of antibodies.
In this aim, we realized experimental investigations in different ruminant species in order to get objective informations and experimental observations on possible side effects of repeated xenogenic gonadotrophic treatments as circulating antibodies in plasma and decreased response to repeated administration. In this aim, we recorded reproductive performances in parallel with measurement of circulating antibodies in plasma using an in vitro radiometric method.
So, ninety-eight goats of two herds were followed over 4 years in a program of annual artificial insemination after estrus induction/synchronization, including progestagen administration (vaginal sponge) followed by prostaglandin analog and equine chorionic gonadotrophin (eCG) 48h before sponge removal. After withdrawal of progestagen, goats were sampled every 4 hours for determination of LH surge and tested for estrus by the presence of a buck. Seven days after AI, endoscopic examination of the ovaries was performed while plasma progesterone was used at day 21-22 after AI for early pregnancy diagnosis. Finally, echography was performed at day 40-45, before monitoring parturition, number and sex of kids. All the goats were sampled before and after each treatment, for anti-eCG antibodies screening. Statistical analysis of the results clearly established a significant effect of the treatments on anti-eCG antibodies while no effect of the herd or of the age of the female. A significant difference was found between the two herds when the delay for coming out of estrus or for LH surge was considered. The antibodies significantly influenced the time of coming out of estrus as well as the time of LH surge. No influence of the age at the first treatment on the time of estrus or the time of LH surge was found. The antibodies after treatment significantly influenced the percentage of ovulating females as well as kidding rate, whatever the age of the female. Finally, no effect of antibodies on prolificacy was found even if antibodies significantly influenced the fertility.
In the following experimental protocol, we verified the possible effect of high frequency of administration on the immune response to eCG. The profiles of eCG binding rate, in the blood of cows submitted weekly for 5 to 10 weeks to repeated high doses (1000-2000 IU) of equine chorionic gonadotrophin in an ovum pick up experimental protocol were followed. The profiles clearly indicated a marked increase of eCG binding rate after 3 to 5 injections of the exogenous hormone to the females. The statistical analysis of the results established that treatments induced a significant increase in binding rates after 6 and 3 injections according to the group. These binding rates remained elevated for at least 1 week following the last injection and decreased afterwards. The values of plasma binding rates following repeated eCG administration differed significantly between groups and from one cow to another with some cows presenting no significant immune response while others were more reactive against the hormone.
Finally, the experiment on sheep consisted in the estimation of the long-term consequences on reproduction performance, of the oestrus synchronization treatments that are annually applied to ewes. In this aim, nine dairy flocks were followed. An hormonal treatment combining the insertion of a vaginal fluoro-gestone acetate (FGA) sponge for 14 days and the injection of about 500 IU of pregnant mare serum gonadotropin (PMSG) at withdrawal was applied to the ewes in seven of the nine flocks. Females of the two other flocks were used as controls. Blood samples were taken from each female just before the treatment (to test for the presence of residual antibodies) and 20 days after the PMSG injection. Anti-PMSG antibody binding rates were calculated for each blood sample. The residual binding rate increased with age and induce negative effects on the following years reproduction performances, i.e., they increased the probability that the ewes would not become pregnant.
