Insights into the role of PGF2α in canine periparturient myometrium.

Parturition in dogs is subjected to complex hormonal regulation, with the involvement of prostaglandin F2α (PGF2α) still not fully understood. To investigate uterine inertia (UI), the most prevalent maternal reason for dystocia in the bitch, a better understanding of undisturbed uterine, especially myometrial function, is crucial. Our aim was to gain deeper insights into the role of PGF2α in the canine parturient myometrium. Uterine biopsies were obtained during medically indicated cesarean sections. To test for stimulatory effects of PGF2α in vitro, circular and longitudinal myometrial layer tissue strips were challenged with 50 pM, 0.5 µM, and 50 µM PGF2α. Prostaglandin-endoperoxide synthase 2 (PTGS2) and PGF2α-receptor (PTGFR) mRNA expressions were compared between primary UI (PUI) and obstructive dystocia (OD) samples in isolated parturient myometrium. PTGFR protein expression was assessed in full thickness uterine samples. PGF2α concentrations were analyzed in canine interplacental tissue around term. In the organ bath, the contractile response to PGF2α was limited to the circular layer at the highest dosage. Correspondingly, PTGFR immunohistochemical staining was significantly stronger in the circular layer (p ≤ 0.01). PTGS2 gene expression did not differ between PUI and OD, whereas PTGFR gene expression could not be quantified. Local uterine PGF2α concentrations correlated negatively with serum P4 levels and were the highest during prepartum luteolysis while being significantly lower in PUI. Conclusively, despite the significant increase in local PGF2α concentrations at birth, confirming the interplacental tissue as a production site, our results suggest that PGF2α might affect uterine contractility during labor, mainly indirectly.

The In Vitro Contractile Response of Canine Pregnant Myometrium to Oxytocin and Denaverine Hydrochloride.

In pregnant bitches, the response to oxytocin and denaverine hydrochloride in dystocia management is usually poor. To better understand the effect of both drugs on myometrial contractility, the circular and longitudinal muscle layers were examined in an organ bath. For each layer, three myometrial strips were stimulated twice, each with one of three oxytocin concentrations. The effect of denaverine hydrochloride was studied once in direct combination with oxytocin and alone with subsequent oxytocin administration. Contractions were recorded and evaluated for average amplitude, mean force, area under the curve (AUC), and frequency. Effects of different treatments were analyzed and compared within and between layers. In the circular layer, oxytocin significantly increased amplitude and mean force compared to untreated controls regardless of stimulation cycles or concentrations. In both layers, high oxytocin concentrations caused tonic contractions, while the lowest concentration created regular rhythmic contractions. Longitudinal layer tissue responded to oxytocin with a significantly decreased contractility when stimulated twice, presumably a sign of desensitization. Denaverine hydrochloride neither affected oxytocin induced contractions nor showed a priming effect to subsequent oxytocin. Thus, no benefit of denaverine hydrochloride on myometrial contractility was found in the organ bath. Our results suggest a better efficiency of low-dose oxytocin in canine dystocia management.

Involvement of Oxytocin and Progesterone Receptor Expression in the Etiology of Canine Uterine Inertia.

An altered oxytocin and progesterone receptor (OXTR and PGR, respectively) expression was postulated in canine uterine inertia (UI), which is the lack of functional myometrial contractions. OXTR and PGR expressions were compared in uterine tissue obtained during C-section due to primary UI (PUI; n = 12) and obstructive dystocia (OD, n = 8). In PUI, the influence of litter size was studied (small/normal/large litter: PUI-S/N/L: n = 5/4/3). Staining intensity in immunohistochemistry was scored for the longitudinal and circular myometrial layer and summarized per dog (IP-Myoscore). Mean P4 did not differ significantly between PUI (n = 9) and OD (n = 7). OXTR and PGR expressions (ratios) were significantly higher in PUI (OXTR: p = 0.0019; PGR: p = 0.0339), also for OXTR in PUI-N versus OD (p = 0.0034). A trend for a higher PGR IP-Myoscore was identified (PUI-N vs. OD, p = 0.0626) as well as an influence of litter size (lowest PGR-Myoscore in PUI-L, p = 0.0391). In conclusion, PUI was not related to higher P4, but potentially increased PGR availability compared to OD. It remains to be clarified whether OXTR is upregulated in PUI due to a counterregulatory mechanism to overcome myometrial quiescence or downregulated in OD due to physiological slow OXTR desensitization associated with an advanced duration of labor. Identified OXTR differences between myometrial layers indicate the need for further research.