A single injection of a long-acting oxytocin analog (carbetocin) at estrus onset synchronizes ovulations and enhances ovulation rate in ewes

Multiple matings during the sexually receptive period is associated with a shorter duration of estrus in small ruminants [[1], [2], [3]], although the physiological mechanism underlying this phenomenon remains unclear. Kendrick et al. [4,5] reported there was an increase in oxytocin (OXT) concentrations in the mediobasal hypothalamus (MBH) in mated ewes when there was intromission and ewes subjected to vaginocervical stimulation (VCS). These authors proposed that the release of OXT from the MBH inhibits sexual receptivity of ewes, leading to a decrease in duration of estrus [5]. This finding is consistent with the effects of progesterone (P4), estrogen, and vaginal stimulation in modulating neural activity in the MBH during sexual receptivity in ewes [6,7], and with the evidence that estrogen regulates the expression of OXT receptors in the MBH of rats [8,9]. Multiple matings lead to a decrease in duration of estrus, which is thought to occur as a consequence of repetitive penis intromission in the female reproductive tract inducing a mechanical afferent stimulus that via the spinal cord is transmitted to the MBH and/or the paraventricular nucleus, inducing central and peripheric release of OXT. It has been reported, however, that systemic administration of OXT does not reduce the duration of in goats [10], possibly due to its short half-life and limited capacity of OXT to be transferred across the blood-brain barrier, which limits the quantity of hormone in the cerebrospinal fluid and, consequently, the potential to induce a central nervous effect.

Furthermore, it has been reported that OXT stimulates pituitary LH secretion in various species, including marmosets [11], rats, humans and dogs [12] as well as horses [13]. This evidence is consistent with the hypothesis that OXT release induced by mating enhances LH secretion, and therefore, modifies the ovulatory processes. Supporting this hypothesis is the assumption that prolonged OXT administration results in an increased ovulation rate (OR) in ewes [14,15], likely due to the suppressive effect of OXT on steroidogenesis. Consistent with this line of thought, it was proposed that the dominant follicle may not secrete sufficient estradiol to suppress pituitary FSH secretion [15], leading to a sustained FSH stimulation of the growth of subordinate follicles.

Carbetocin is a synthetic OXT analog with a half-life at least ten times longer than that of OXT in cattle [16], and is apparently transported across the blood-brain barrier in rats [17]. These characteristics result in Carbetocin having central and sustained effects in various brain regions, including hypothalamic centers involved in sexual behavior, as well as peripheral effects on the reproductive tract. Thus, Carbetocin may serve as a potential pharmacological agent for mimicking the central effects of OXT when released in response to mating during spontaneous estrus. Considering that multiple matings lead to an increase in size of the preovulatory follicle, enhanced corpus luteum (CL) function, and increased P4 secretion in ewes [3], and considering the possibility that these effects are mediated by OXT, we hypothesized that a single injection of Carbetocin reduces the estrous duration, and affects the ovarian follicular and luteal function in ewes. Therefore, the aim of the present study was to compare sexual receptivity, ovarian follicular development, timing of ovulation, and luteal function in ewes treated or not with Carbetocin.

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