Pyometra and estrous cycle modulate the uterine expression of the kisspeptin system and angiogenic and immune factors in cats

Abstract

Failures in hypothalamic kisspeptin/Kiss1r signaling are associated with infertility, and in vitro studies have shown that kisspeptin can modulate angiogenesis and immune activity. Because there is no in vivo research on the functional relationship between these factors in the reproductive system, especially in domestic cats, we evaluated the expression profile of kisspeptin/Kiss1r and angiogenic and immunological mediators in the genital tract of cyclic cats and of those with pyometra. The uterus of cats in diestrus exhibited greater gene and protein expression of Kiss1, as well as Vegf, Pigf, Mif, and Il6. In contrast, Kiss1r presented greater expression in proestrus/estrus, similarly to that observed for the immunostaining of INFγ, MIF, TNFα, and IL10. These factors were positively correlated with Kiss1 and/or Kiss1r, and a positive correlation between Kiss1 and Kiss1r was also observed in the uterus of cats during the estrous cycle. Cats with pyometra showed greater immunostaining of Kiss1 and Kiss1r on the endometrial surface and reduced immunostaining of Kiss1 in deep glands, whereas there was a significant reduction in Vegf, Pigf, Mif, and Il6 mRNA, and an increase in Tnf mRNA. The findings reveal that there is a gene correlation between kisspeptin/Kiss1r and angiogenic and immune mediators in the uterus of the domestic cat, which are modulated by the estrous cycle, and that pyometra affects the expression of these mediators. This study suggests, for the first time, a functional relationship between the Kiss/Kiss1r system and angiogenic and immune mediators in the female genital tract.

Vascular endothelial growth factor (VEGF) expression in histological endometritis in the bitch: An immunohistochemical study

“…Veiga et al (2017) reported increased VEGF and VEGFR expression in bitches with pyometra. These results agree with Santos et al (2021) reported in VEGFR-1 but not VEGF.…”

“…However, VEGF showed no differences in the %MA. Interestingly, a recent study reported controversial results in the endometrial expression of VEGF and VEGFR‐1 in cats with pyometra (Santos et al, 2021). In that study, females presented higher VEGFR‐1 expression and lower VEGF expression than healthy females, agreeing with our results in END for the area.…”

Pyometra alters the redox status and expression of estrogen and progesterone receptors in the uterus of domestic cats

“…The nega tive control was obtained by replacing the primary anti body with phosphatebuffered saline. 20 Descriptive and quantitative evaluation of the immu nohistochemical staining of PR, ERα, AR, catalase, SOD1, and GPX1/2 in the uterus was performed. In the descrip tive analysis, luminal epithelium, glandular epithelium, stromal and myometrial cells were evaluated in the uterus.…”

“…Data from each tissue were archived, ana lyzed and expressed as immunostaining area in pixels. 20 qPCR For the qPCR technique, the extraction of total RNA from the uterus was performed using Trizol (Invitrogen, Life Technologies) following the kit protocol. Then, 1 µg of RNA was used for complementary DNA (cDNA) syn thesis using the GoTaq 2Step RTqPCR System (A6010).…”

“…We have recently demonstrated that the uterine expression of kisspeptin and its receptor Kiss1R, as well as angiogenic and immunological mediators, such as vascular endothelial growth factor, placental growth factor, interleukin-10, tumor necrosis factor, interleukin-6, and macrophage migration inhibitory factor, are altered in the uterus of cats with pyometra, and these mediators also influence tissue oxidative balance. 19 – 21 However, to date, there are no studies that have evaluated the profile of antioxidant enzymes and the occurrence of oxidative stress in the uterus of cats with pyometra.…”