Cystic endometrial hyperplasia–pyometra syndrome in bitches: identification of hemodynamic, inflammatory, and cell proliferation changes^{<xref ref-type="fn" rid="afn1">†</xref>}

Abstract

Cystic endometrial hyperplasia (CEH)-pyometra syndrome is one of the most common diseases of noncastrated female dogs. However, determination of etiological mechanisms and differential diagnosis of CEH-pyometra syndrome are undefined. The aim of this study is to compare immunohistochemically the expression of cyclooxygenase-2 (COX-2) inflammatory mediator, Ki-67 antigen proliferation marker, vascular endothelial growth factor (VEGF-A) angiogenesis mediator and its FLT-1 and KDR receptors, and correlate with Doppler velocimetry of uterine artery and endometrial vascularization in bitches with CEH-pyometra syndrome. Bitches were allocated into CEH-mucometra Group (n = 13), Pyometra Group (n = 11), and Control Group (n = 8). Pyometra Group presented cytoplasmatic staining intensity for COX-2, VEGF-A, and FLT-1 and KDR receptors in luminal epithelium cells significantly higher compared to CEH-mucometra and Control groups. For the glandular epithelium, Pyometra Group had higher immunostaining score for VEGF-A and its receptors (FLT-1 and KDR). Hemodynamic indexes showed negative correlation with VEGF-A and its receptors as well as with COX-2. On the other hand, uterine vascularization score showed positive correlation in relation to immunostaining of COX-2, VEGF-A, and receptors in the endometrium luminal epithelium. In conclusion, uterus of bitches with CEH-pyometra syndrome show inflammatory process characterized by COX-2 expression, resulting in greater expression of proliferative Ki-67 marker as tissue response against the infectious agent. Furthermore, the increased VEGF-A expression and its receptors in CEH-pyometra reflect the increased blood flow and lower vascular resistance. Therefore, canine pyometra is characterized by an inflammatory, proliferative, and vascular disorder.

Prostatic hyperplasia: Vascularization, hemodynamic and hormonal analysis of dogs treated with finasteride or orchiectomy

“…Our data show that untreated PH dogs had the highest vascularization score throughout the experimental period, as well as the highest immunostaining score for VEGF-A in the prostate epithelium, similarly to previous data on men [49,50] and dogs [35,51,52]. Moreover, positive correlation between prostate volume and local blood flow was observed for untreated and finasteride-treated dogs, suggesting that increased prostatic size is followed by a concomitant increase in local vascularization in PH dogs [18,20,31].…”

“…All immunohistochemical reactions were accompanied by a negative control as previously described [31,32], consisted of prostate tissue from the Untreated Group lacking application of primary antibody. For the positive control, we used canine mammary gland tumor, previously attested by others [33][34][35] and also as a guarantee of the cross-reactivity of the primary antibody with canine tissue.…”

Uterine two‐dimensional and Doppler ultrasonographic evaluation of feline pyometra

“…It has been suggested that during early feline pregnancy matrix metalloproteinases increase, playing an important role in vascularization and implantation (Agaoglu et al, 2016). In the case of pyometra, vascular endothelial growth factor and prostaglandins are the molecular mediators that may be involved in the vascular changes (Hagman, 2017;Jursza-Piotrowska & Siemieniuch, 2016;Veiga et al, 2017). The dissimilar signal pathways activated in these processes might explain the uterine blood flow difference found between PYO and PRG groups.…”

“…In dogs, Doppler ultrasound has proved to be able to differentiate pyometra from other uterine conditions (Batista et al, 2016;Veiga et al, 2017). However, the use of Doppler ultrasound to assess feline pyometra has not been reported so far.…”

Advanced ultrasound techniques in small animal reproduction imaging

“…In bitches with pyometra, endometrial hyperplasia, with or without luminal content, the uterine artery blood flow velocity was higher than in normal ones (Batista et al, 2016). Uteri of bitches with cystic endometrial hyperplasia-pyometra syndrome showed inflammatory process characterized by COX-2 expression, resulting in not only inflammatory and proliferative, but also vascular disorders, demonstrated by increased blood flow and lower vascular resistance (Veiga et al, 2017). In 2018, Doppler was also used to evaluate pyometra in cats.…”