Acute Injection and Chronic Perfusion of Kisspeptin Elicit Gonadotropins Release but Fail to Trigger Ovulation in the Mare1

Abstract

Kisspeptin has emerged as the most potent gonadotropin-releasing hormone (GnRH) secretagogue and appears to represent the penultimate step in the central control of reproduction. In the sheep, we showed that kisspeptin could be used to manipulate gonadotropin secretion and control ovulation. Prompted by these results, we decided to investigate whether kisspeptin could be used as an ovulation-inducing agent in another photoperiodic domestic mammal, the horse. Equine kisspeptin-10 (eKp10) was administered intravenously as bolus injections or short- to long-term perfusions to Welsh pony mares, either during the anestrus season or at various stages of the cycle during the breeding season. In all the experimental conditions, eKp10 reliably increased peripheral concentrations of both luteinizing hormone and follicle-stimulating hormone. The nature of the response to eKp10 was consistent across experimental conditions and physiological states: the increase in gonadotropins was always rapid and essentially transient even when eKp10 was perfused for prolonged periods. Furthermore, eKp10 consistently failed to induce ovulation in the mare. To gain insights into the underlying mechanisms, we used acute injections or perfusions of GnRH. We also cloned the equine orthologues of the kisspeptin precursor and Kiss1r; this was justified by the facts that the current equine genome assembly predicted an amino acid difference between eKp10 and Kp10 in other species while an equine orthologue for Kiss1r was missing altogether. In light of these findings, potential reasons for the divergence in the response to kisspeptin between ewe and mare are discussed. Our data highlight that kisspeptin is not a universal ovulation-inducing agent.

An administration of TAK-683 at a minimally effective dose for luteinizing hormone stimulation under the absence of the ovary induces luteinizing hormone surge in ovary-intact goats

“…For example, a single treatment of the kisspeptin-10 or kisspeptin receptor agonist (FTM080) resulted in a short-term increase in plasma levels of LH in anestrous ewes [17]. The effects of intravenous administration of a single bolus of kisspeptin-10 elicited LH secretion with a relatively small amplitude and a short duration (for several hours), but failed to induce LH surge and ovulation in mares [18]. On the other hand, constant infusion of kisspeptin-10 produced a sustained increase in plasma levels of LH during the infusion period with the equivalent peak values of endogenous LH surge in ewes [19].…”

Kisspeptin and the regulation of the reproductive axis in domestic animals

“…Anterior pituitary secretion of the gonadotrophin, luteinising hormone (LH), then acts as an amplifier to the GnRH signal (Clarke & Cummins 1982). In sheep, at least, the neurons that produce GnRH receive relatively little synaptic input compared to other neurons within the hypothalamus (Lehman et al 1988, Magee et al 2009, Decourt et al 2014, McGrath et al 2016. Thus, it would seem likely that much of the integration of the various factors that influence GnRH secretion occurs upstream of the GnRH neuron.…”

Review: kisspeptin and reproduction in the pig

“…The initial kisspeptin-induced increase in LH and FSH was followed subsequently by increasing the concentrations of oestradiol from developing follicles that were critical for the induction of the subsequent LH surge. Similar increases in LH and FSH were seen with kisspeptin treatment in the mare, but kisspeptin failed to stimulate ovulation (Magee et al, 2009;Decourt et al, 2014). Important differences between mares and ewes are that mares are oestrus for a longer duration, the timing of the ovulatory LH surge relative to the start of oestrus is more variable, and the LH surge is more protracted.…”

“…The potential for kisspeptin to be useful in managing reproductive cycles and ovulation in livestock is obvious. The bulk of the work in this area has been conducted in sheep (Redmond et al, 2011b) with a few studies in cattle (Whitlock et al, 2008;Ezzat Ahmed et al, 2009) and mares Lents (Magee et al, 2009;Decourt et al, 2014). These studies encompass a wide range of differences in seasonality, presence of gonadal steroid feedback, stage of the ovarian cycle and state of sexual maturation that must be taken into careful consideration when comparing studies.…”