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

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 II6. In contrast, Kiss1r presented greater expression in proestrus/estrus, similarly to that observed for the immunostaining of INF gamma, MIF, TNF alpha, and IL10. These factors were positively correlated with Kiss1 and/or Kisslr, and a positive correlation between Kiss1 and Kisslr was also observed in the uterus of cats during the estrous cycle. Cats with pyometra showed greater immunostaining of Kiss1 and Kisslr on the endometrial surface and reduced immunostaining of Kiss1 in deep glands, whereas there was a significant reduction in Vegf, Pigf, Mif, and II6 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 is 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.

Automated summary

Failures in hypothalamic kisspeptin/Kiss1r signaling are linked to infertility, and in vitro studies suggest kisspeptin may affect angiogenesis and immune activity. This study explored the gene correlation between kisspeptin/Kiss1r and angiogenic and immune mediators in the uterus of domestic cats, highlighting the impact of the estrous cycle and pyometra on the expression of these factors.