# Endocannabinoid System Regulation in Pyometra-Affected and Healthy Canine Uteri

## TL;DR

This study explores the role of the endocannabinoid system in the uteruses of dogs with and without pyometra, revealing its potential importance in inflammation and reproduction.

## Contribution

The study is the first to demonstrate a functional endocannabinoid system in the canine uterus and its modulation during pyometra.

## Key findings

- The canine uterus has a functional endocannabinoid system with specific receptor expression patterns.
- Endocannabinoid levels and receptor activity are linked to reproductive status and pyometra-related inflammation.
- Serum anandamide levels were significantly reduced in closed-cervix pyometra compared to anestrus.

## Abstract

Pyometra is a common and potentially life-threatening uterine infection in female dogs, characterized by strong immune and inflammatory reactions. The endocannabinoid system (eCS) is known to regulate immunity and inflammation in the body, but its role in the canine uterus has not been studied. In this study, we examined uterine tissues from pyometra-affected and healthy dogs to investigate the presence of eCS components. We analyzed endocannabinoids in the serum and evaluated their receptor expression in the uterus. Our results show that the canine uterus has a functional eCS, with specific patterns of receptor expression, and that changes in this system are associated with reproductive status and inflammatory responses during pyometra. These findings provide new insights into uterine physiology and potential therapeutic targets for canine pyometra.

Pyometra is a frequent and life-threatening reproductive disorder in bitches, characterized by profound immune and inflammatory responses within the uterus. The endocannabinoid system (eCS) is a key modulator of immune regulation, tissue homeostasis, and inflammation; however, its role in canine uterine physiology and pathology remains unexplored. This study aimed to characterize the presence and regulation of eCS components in the uterus of healthy and pyometra-affected dogs. Twenty-eight bitches were categorized into four groups: closed-cervix pyometra (CP; n = 7), open-cervix pyometra (OP; n = 7), diestrus (DE; n = 7), and anestrus (AE; n = 7). Uterine tissues were obtained by ovariohysterectomy. Serum progesterone, anandamide (AEA), and 2-arachidonylglycerol (2-AG) concentrations were quantified, while the uterine expression of cannabinoid receptors (CB1 and CB2) was assessed using real-time PCR and localized by immunohistochemistry (IHC). Serum AEA levels were significantly reduced in CP compared with AE (p = 0.017), whereas 2-AG differences did not reach significance (p = 0.072). Both CB1 and CB2 were consistently expressed across all groups, with IHC revealing receptor-specific patterns within uterine compartments. Collectively, these findings demonstrate for the first time that the canine uterus possesses a functional eCS, and that its modulation is linked to reproductive physiology and pyometra-associated inflammatory processes.