Do uterine PTGS2, PGFS, and PTGFR expression play a role in canine uterine inertia?

Abstract

The aetiology of primary uterine inertia (PUI), which is the most common cause of canine dystocia, is still not elucidated. Prostaglandins (PGs) play a crucial role in parturition. We hypothesized that the expression of prostaglandin endoperoxidase synthase 2 (PTGS2), PGF2α synthase (PGFS), and corresponding receptor (PTGFR) is altered in PUI. We investigated PTGS2, PGFS, and PTGFR mRNA expression, and PTGS2 and PGFS protein expression in interplacental (IP) and uteroplacental sites (UP) in bitches with PUI, obstructive dystocia (OD), and prepartum (PC). PTGS2, PGFS, and PTGFR mRNA expression did not differ significantly between PUI and OD (IP/UP). PTGFR ratio in UP was higher in PC than in OD (p = 0.014). PTGS2 immunopositivity was noted in foetal trophoblasts, luminal and superficial glandular epithelial cells, smooth muscle cells of both myometrial layers, and weakly and sporadically in deep uterine glands. PGFS was localized in luminal epithelial cells and in the epithelium of superficial uterine glands. PTGS2 and PGFS staining was similar between PUI and OD, while PGFS protein expression differed between OD and PC (p = 0.0215). For PTGS2, the longitudinal myometrial layer of IP stained significantly stronger than the circular layer, independent of groups. These results do not support a role for PTGS2, PGFS, and PTGFR in PUI. Reduced PGFS expression in IP during parturition compared with PC and the overall lack of placental PGFS expression confirm that PGFS is not the main source of prepartal PGF2alpha increase. The difference in PTGS2 expression between IP myometrial layers warrants further investigation into its physiological relevance.

Implications of the RhoA/Rho associated kinase pathway and leptin in primary uterine inertia in the dog

“…Similar changes in uterine mRNA expression of smooth muscle γ-actin and myosin between PUI and OD bitches [8], or in oxytocin receptor expression between dogs in labor with dystocia and undergoing elective CS [16] were found before, but not for uterine expression of prostaglandin-endoperoxidase synthase 2 and the PGF2α pathway [14]. These differences seen here may be due to abnormal labor signaling, or protracted or inadequate uterine response in PUI bitches.…”

“…Recently, advances were made in identifying defects in the contractile properties of the uterus at the cellular and molecular level. Our group showed that bitches diagnosed with PUI had higher uterine mRNA expression levels of smooth muscle γ-actin and smooth muscle myosin than dogs in labor still showing strong contractions [8], while gene expression of members of the prostaglandin (PG) F2α and PGE pathway did not differ [14,15]. Changes in uterine oxytocin receptor expression also did not seem to be implicated in the development of PUI [16].…”

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

“…Despite the frequent occurrence of PUI in dogs and its severe consequences for maternal and offspring survival, the exact etiology is still unknown. Up to now, only few studies have investigated its pathophysiology from a molecular biology approach looking directly at the level of the uterus [ 16 , 17 , 32 , 45 , 46 ]. As both oxytocin and progesterone are crucial hormones during parturition, we hypothesized and identified altered expression of the respective receptors as potential causes for PUI.…”

“…The significantly higher OXTR mRNA expression (ratio) in IP samples obtained from PUI (and PUI-N) dams compared to OD might be a consequence of the absence of intracervical pressure due to the fact that no puppy had been born and, thus, having insufficient systemic OXT release, as previously postulated by Tamminen et al [ 32 ]. It is worth noting that comparison of the OD and PUI samples was shown to be suitable in previous studies to gain further insight into the pathophysiology of canine dystocia and specifically PUI [ 15 , 16 , 17 , 32 , 45 , 46 ].…”

“…In contrast to this, Gogny et al [ 61 ] described a greater contractile response to OXT in the longitudinal compared to the circular myometrial layer of cyclic healthy bitches in anestrus or metestrus with and without Aglepristone treatment. Recently, our working group investigating the role of prostaglandins in PUI identified a significant difference in PTGS2 staining between myometrial layers, with PTGS2 being higher-expressed in the longitudinal layer of the same samples [ 46 ]. Taken together, all studies suggest a complex regulation of myometrial contractile activity during parturition with coordinated action of the two myometrial layers in canine uterine tissues being essential for eutocia.…”