Effects of Topical Application of Misoprostol on Cervical Relaxation in Mares

Abstract

Mares who have not delivered a foal early in life may experience limitations in cervical relaxation, primarily during oestrus. A closed cervix prevents intrauterine deposition of semen during natural breeding, may delay uterine clearance after insemination leading to intrauterine fluid accumulation in, and subsequent infertility. Therefore, a reliable pharmacological method of dilating the equine cervix would have practical application in veterinary medicine. The goal of this study was to investigate the effectiveness of topically applied, synthetic prostaglandin E1 analogue (PGE1 ) for stimulating dilation of the equine cervix. Ten mares in dioestrus were randomly assigned to one of two treatments in a single-blind crossover study: (treatment) PGE1 gel (1000 mcg compounded misoprostol cream) applied topically to the external cervical os (n = 5), and (control) a vehicle cream applied topically to the external cervical os (n = 5). Transrectal palpation and ultrasonographic measurements of the cervix were performed prior to, six and 24 h post-treatment. Digital measurements were taken, per vagina, at six and 24 h post-treatment. Mares were monitored through the subsequent oestrous cycle for ovulation. Mares were assigned to the opposite treatment group such that each mare served as her own control (crossover). Data were analysed using parametric (split-plot anova), as well as nonparametric (Kruskal-Wallis anova, Wilcoxon's rank-sum test) methods. At six and 24 h there were no significant differences for tone, length, height, degree of relaxation or echotexture between control and PGE1 treated groups at the measured time points (p > 0.05). Topical cervical application of PGE1 did not induce a measurable degree of cervical relaxation under the conditions of this experiment.

Effect of oral misoprostol, alone or in combination with aglepristone, on mid-term pregnancy termination in cats

“…After having been used in human medicine, MIS has been tested in veterinary gynaecology for pregnancy termination, induction of parturition or cervical ripening in dogs, ewes, goats, cows and mares. 10,[20][21][22][23][24][25] There are no reports of health risks associated with this drug, and the results have been successful in the aforementioned studies, according to the study authors. The drug can be safely used in dogs and rats in a wide dose margin without causing any acute or chronic systemic dysfunction.…”

Oral misoprostol does not hasten oviductal transport of day-5 horse embryos

“…Horses, however, may have a different receptor interaction with misoprostol than other species. Misoprostol induces early abortions and uterine contractility in humans (Zhang et al 2015;Bilgin and Komurcu, 2019), but it has no adverse effects in pregnant mares (Jacobson et al 2013;Linton and McDonnell, 2014), and its effects when administered locally in substitution for PGE2 for cervical relaxation is controversial (McNaughten et al, 2014). Blikslager (2013) hypothesized that a variant of the EP3 receptor with low-affinity and of unknown relevance in myometrial cells, may be …"the mechanism whereby misoprostol has less of an effect on contraction of urogenital smooth muscle as compared with PGE2"… (Blikslager, 2013).…”

“…Conversely, when misoprostol was administered orally, there were no adverse effects when there was treatment of pregnant mares during early (Linton and McDonnell, 2014) or mid-gestation (Jacobson et al, 2013). Furthermore, the intra-cervical administration of PGE2 for induction of cervical relaxation in mares (Nie and Barnes, 2003;LeBlanc, 2006) is controversial (McNaughten et al, 2014). There is intra-uterine administration of misoprostol directly onto the oviductal papilla for the treatment of presumptive blockage of the oviducts (Alvarenga and Segabinazzi, 2018).…”