Primary Uterine Inertia (PUI) in Dogs Is Associated with Impaired Placental Availability of Factors Involved in the Parturition Cascade

Abstract

The canine parturition cascade involves decreased placental progesterone (P4) signaling mediated through its nuclear receptor PGR in decidual cells, leading to increased trophoblast production of PGF2&alpha; that promotes luteolysis, placentolysis, and myometrial contractility. A local role for glucocorticoids in initiating parturition through increased placental availability of cortisol and glucocorticoid receptor (<i>GR</i>/<i>NR3C1</i>), possibly affecting P4-PGR signaling, has been suggested. Primary uterine inertia (PUI) is a major cause of canine dystocia, but its pathophysiology remains unclear. Here, we hypothesized that dysregulated placental signaling could contribute to PUI. The availability of parturition cascade-related factors was assessed in placentae of dogs with PUI and during physiological prepartum luteolysis (LUT). Compared with LUT, PUI had no significant changes in prostaglandin-related factors <i>PTGS2</i>, <i>PTGES</i>, and <i>HPGD</i> (<i>p</i> &gt; 0.05), but had lower PGF2&alpha; synthase <i>PGFS</i>/<i>AKR1C3</i> (<i>p</i> &lt; 0.001), and higher <i>PGT</i> abundance (<i>p</i> &lt; 0.001). PUI had increased PGR transcript and protein levels (<i>p</i> &lt; 0.001), but the same number of decidual cells (<i>p</i> &gt; 0.05). <i>GR</i>/<i>NR3C1</i> availability was reduced in PUI (<i>p</i> &lt; 0.05), along with decreased placental cortisol-to-cortisone conversion. Our findings suggest that PUI could be associated with disturbances of the parturition cascade, possibly due to inadequate P4-PGR and glucocorticoid signaling in the placenta.