Progestogen priming is not essential to trigger ovulation in seasonal anoestrus ewes injected twice with a synthetic kisspeptin analogue

A key aspect of husbandry is reproduction management, and current methods often rely on the use of hormonal treatments. In the ewe, which is a seasonal breeder, a combination of progestogen and equine Chorionic Gonadotropin is the benchmark method for reproduction control. However, for different reasons, these hormones are leading to an increase in societal aversion. In order to find an alternative to their use, we have designed a synthetic analogue (C6) of kisspeptin, a key neurotransmitter in reproduction control. In the present study, we evaluated whether C6 could be used to replace hormones to induce ovulation and a luteal phase in ewes during the non-breeding season. Previous knowledge indicates that a single injection of C6 is unable to trigger ovulation unless preceded by progesterone priming; therefore, we tested a combination of two injections. We spaced injections at 24, 36 or 48 h. For the first injection, we used either 2.5 or 15 nmol, whereas the dose of the second injection was 15 nmol for all experimental groups. The combination of 15+15 nmol doses injected 48 h apart proved the most efficacious. It induced ovulation and a luteal phase in more than 60% of treated ewes as established by progesterone blood concentration. To assess if a specific hormonal footprint could be associated with ewes that ovulated, we analysed the time course of LH, FSH and estradiol plasma concentrations. However, no specific hormonal signature indicative of treatment success could be pinpointed. This study shows that it is possible to induce ovulation and a luteal phase in ewes during the non-breeding season by replacing hormonal treatment with a double injection of C6. Nonetheless, further optimisation of the method is required to reach the efficacy of benchmark treatment.