Canine uterine inertia – Are oxytocin and progesterone receptors part of the etiology?

Oxytocin and progesterone are important in the endocrine network of canine parturition. As uterine inertia is associated with lack of appropriate myometrial contractions, we postulated altered oxytocin receptor (OXTR) and progesterone receptor (PGR) expression being causally involved.

Interplacental tissue samples obtained during medically indicated Caesarean section were grouped into “primary uterine inertia” (PUI; n=12) or “obstructive dystocia” (OD, n=8). Subgroups according to mean breed-specific litter size were formed within PUI (small/normal/large litter: PUI-S/N/L: n=5/4/3). Serum progesterone concentrations were assessed using radioimmunoassay. Uterine OXTR and PGR expressions were investigated using efficiency-corrected qPCR (ratios) and immunohistochemistry. Staining intensity was scored (0-3) separately for the longitudinal and circular myometrial layer and summarized per dog as MyoScore. Ratios and MyoScore were statistically compared between PUI/PUI-N and OD. The longitudinal and circular layer were compared in all samples and within groups.

OXTR and PGR expressions (ratios) were higher in PUI compared to OD (OXTR: p=0.0019; PGR: p=0.0339), and OXTR differed between PUI-N and OD (p=0.0034). Similarly, a trend for higher PGR MyoScores was identified (PUI/PUI-N versus OD; p=0.0716/p=0.0626). Interestingly, the circular layer stained significantly stronger for OXTR than the longitudinal layer (for PUI+OD: p=0.0001). Litter size influenced PGR-MyoScore (PUI-L < PUI-N/S; p=0.0391), but not mRNA expression.

As progesterone withdrawal is essential for labor initiation, increased PGR expression may be involved in PUI, especially as peripheral progesterone [R1] did not differ between groups. Whether upregulation of OXTR at the mRNA level is a counterregulatory mechanism related to low oxytocin concentrations needs to be further investigated. Nevertheless, our findings support the hypothesis of OXTR and PGR involvement in the etiology of canine uterine inertia.

Supported by Bayer Animal Health GmbH, Dansk Kennel Klub and Gesellschaft der Freunde der Tierärztlichen Hochschule Hannover e.V.