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Pseudoplacentational endometrial hyperplasia (PEH) is a common uterine lesion in dogs. A high frequency of pyometra has been associated with PEH in dogs, suggesting that PEH might be related to the pathogenesis of pyometra. This study aimed to assess transcription levels and expression of Toll like receptors (TLR) 1, 2 and 4; alpha estrogen receptors (ESR1), progesterone receptors (PR) and prolactin receptors (PRLR) in uteri with PEH. Furthermore, the inflammatory response of dog endometrium with PEH against ex vivo bacterial stimulus was also investigated. Uteri were classified as controls or with PEH. Uterine explants were cultured for 6 and 12 hours after in vitro stimulus with inactivated Escherichia coli . Transcription of receptors and proinflammatory cytokines, namely interleukin-6 ( IL-6 ) and CXCL8 were evaluated. Expression of receptors was also evaluated in uterine explants and uteri from biopsy archives. CXCL8 concentration was measured in supernatants from all cultured explants. Transcription levels and expression of both PR and ESR1 were lower in uteri explants with PEH not stimulated and cultured for 6 hours. Expression of PRLR was higher in uteri with PEH from biopsy archives. Proinflammatory response by transcription levels of interleukin 6 demonstrated downregulation in uteri with PEH at 6 hours of stimulation followed by upregulation at 12 hours. However, no differences between groups were observed. Both control and uteri with PEH secreted similar concentrations of CXCL8 at 6 hours of bacterial stimulation. At 12 hours, no response to stimulation was observed in the PEH group and supernatant concentrations of CXCL8 were higher in the control group. The inflammatory response to bacterial stimulus in uteri with PEH had different pattern than the control group, with an inversion in IL-6 transcription levels between 6–12 hours of culture. Additionally, CXCL8 production ceased earlier in explants with PEH than in control.

Background Nesfatin-1 is a neuropeptide that regulates the hypothalamic-pituitary-gonadal axis and may play a role in uterus function. It is co-expressed with other peptides, such as phoenixin, which can influence sex hormone secretion. Our previous research has confirmed that phoenixin-14 is involved in the development of cystic endometrial hyperplasia (CEH) and pyometra in dogs. Therefore, based on the similarities and interactions between these neuropeptides, we hypothesized that nesfatin-1 might also regulate the reproductive system in dogs. This study aimed to determine the expression of nesfatin-1 and its interaction with phoenixin-14 in dogs with CEH or pyometra compared to healthy females, and concerning animals’ body condition score (BCS 4–5/9 vs. BCS > 5/9). Results The analysis of nesfatin-1 in the uterus of bitches consisted of qPCR, western blot and immunofluorescence assays, and ELISAs. The results showed significantly higher nesfatin-1 encoding gene, nucleobindin-2 mRNA ( Nucb2 ) and nesfatin-1 protein expression in overweight females and those suffering from CEH or pyometra compared to healthy animals. The immunoreactivity of nesfatin-1 was elevated in the uteri of bitches with higher BCS > 5/9. Moreover, nesfatin-1 blood concentrations increased in all examined overweight bitches. In the case of phoenixin signals, we found opposite results, regardless of the female body condition score. Conclusion The etiology of CEH and pyometra are not fully known, although we have expanded the level of knowledge with respect to the possible interaction of nesfatin-1 and phoenixin in female dogs’ uteri. They interact oppositely. With increasing female body weight, the expression of nesfatin-1 in the uterus and its peripheral blood concentration increased. However, for female dogs affected by CEH and pyometra, a decreased level of phoenixin-14, irrespective of their body condition score is characteristic. This knowledge could be crucial in the development of biomarkers for these conditions, which may lead to earlier recognition.

The medical records of 59 rabbits with uterine disorders were assessed retrospectively. Ten animals were presented because of vaginal discharge; the reasons for presentation of the remaining 49 rabbits included mammary masses, skin tumours, anorexia and poor general health. All the rabbits underwent a clinical examination, and 54 were examined by ultrasonography and/or radiography. Forty-five rabbits underwent ovariohysterectomy and the other 14 rabbits were euthanased, three because of pulmonary metastases and 11 because of very poor health unrelated to their uterine disease. The genital tracts of all the rabbits were submitted for histological examination. Endometrial hyperplasia (in 24 rabbits) and adenocarcinoma (in 18 rabbits) were the most common uterine disorders; in a further 11 cases both conditions were observed. The remaining six rabbits had other uterine disorders. Four rabbits that were presented with adenocarcinoma of the mammary gland were found to have concurrent uterine disorders. The mean age of the rabbits with endometrial hyperplasia was 4·5 years, and that of the rabbits with adenocarcinoma was 6·1 years. Four rabbits had ovarian tumours.

During a routine geriatric examination on a 9-yr-old, nulliparous female African warthog (Phacochoerus africanus), a severely enlarged, mixed echogenicity uterus was discovered during transabdominal ultrasound. Ovariohysterectomy (OVH) was elected and performed due to concern for a potential neoplastic condition. Postoperatively, the warthog was treated prophylactically with metoclopramide and ranitidine to promote gastrointestinal motility and prevent postoperative ileus. The gross appearance and histopathology confirmed the presence of extensive widely disseminated cystic changes consistent with cystic endometrial hyperplasia (CEH) and multiple para-ovarian cysts. Uterine pathology, including CEH, is a common condition in domestic potbellied pigs (Sus scrofa), and as a result, it is recommended to perform an OVH at an early age. The advanced uterine changes may have accounted for this animal's history of infertility. This case provides evidence that nulliparity may be associated with the development of uterine pathology in warthogs. Increased knowledge of reproductive pathology will aid in improved management strategies for breeding nondomestic suids.

Pyometra and cystic endometrial hyperplasia are common in domestic canids and are suspected to develop as a consequence of elevated progesterone levels. Reports of uterine pathology in exotic canids are limited, with some speculating of association with contraception. This report describes pyometra, cystic endometrial hyperplasia, and ovariohysterectomy in three African hunting dogs (Lycaon pictus). Ovarian corpora lutea were detected in two of the dogs, suggesting endogenous progesterone production. One dog had a uterine adenocarcinoma and two had ovarian granulosa cell tumors. Clinical signs included anorexia, lethargy, vulvar discharge, polyuria, polydipsia, and abdominal distention. Diagnosis was based on clinical signs, physical examination, bloodwork, radiography, and ultrasonography, with confirmation through histopathologic evaluation of tissues. Cystic endometrial hyperplasia, pyometra, and uterine neoplasia have rarely been diagnosed in exotic canids; however, they should be considered as differential diagnoses in intact bitches that present with suspected reproductive disease.

Twenty-two bitches with ultrasonographically diagnosed spontaneous pyometra were treated with a combination of 5 μg/kg cabergoline per day and 5 μg/kg cloprostenol every third day, and potentiated sulphonamide twice a day. Bitches with either open-cervix or closed-cervix pyometra showed a rapid clinical improvement, associated with a reduction in plasma progesterone concentration, increased vulval discharge and a reduction in the diameter of the uterus. The haematological profiles of 21 of the bitches returned to normal within six days of treatment, and their biochemical profiles returned to normal within nine days; 19 of the bitches were managed successfully by a 10-day period of treatment. Two bitches required a further three days of treatment, and in one bitch with a partial uterine torsion the treatment was not successful. Adverse effects of the treatment were limited to the 60 minutes immediately after the administration of prostaglandin, and included retching, vomiting, mild abdominal straining, diarrhoea and panting. The incidence of adverse effects was reduced after each successive dose of prostaglandin. Eleven of the 21 successfully treated bitches were mated at the next oestrus, and seven became pregnant; their litters were smaller than the published breed averages. In four of the bitches the pyometra recurred after the next oestrus.

Kynurenic acid (KYNA) is produced enzymatically in humans and animals from kynurenine. Reports concerning changes of kynurenine metabolism during inflammation are available in the literature. Pyometra is a pathological condition characterized by the accumulation of pus in the uterine lumen and bacterial infection. The objective of the study was to compare the serum and endometrial KYNA concentrations in healthy bitches and those with pyometra. KYNA was determined by means of high-performance liquid chromatography with fluorometric detection. The serum content of KYNA in bitches with pyometra was significantly higher than in healthy bitches. The KYNA content in the endometrium of bitches with pyometra was higher, yet the difference was not statistically significant. Our result indicates that determination of KYNA might be a marker of pyometra in bitches.

A case-control study of 953 dogs with pyometra and 10,660 unmatched control dogs was used to investigate the relationships between age, parity, hormonal therapy and breed, and pyometra in Finnish dogs. Cases were reported in animals between nine months and 18 years of age, with a median age at diagnosis of nine years. Nulliparous bitches had a moderately higher risk of developing pyometra than primiparous and multiparous animals (adjusted odds ratio point estimate, 6.63). The administration of oestrogen increased the risk of pyometra in bitches up to four years of age (odds ratio point estimate >6). No significant risk-enhancing effect of progestin treatment was detected and it is unlikely that such a risk, if present, is high (likelihood of the odds ratio exceeding 2 <0.18). Seventeen breeds had an increased risk, and the wire-haired dachshund and mongrels had a decreased risk of developing the condition.