Molecular Factors Involved in the Pathogenesis of Pyometra in Domestic Cats (Felis catus)

Abstract

Pyometra is a major reproductive disorder affecting female cats. Characterized by the accumulation of purulent exudate in the uterus, it can lead to severe and potentially fatal complications. This pathology primarily occurs in adult cats during diestrus, but can also affect younger felines, often due to inappropriate administration of hormonal medications. While the etiopathogenesis of pyometra is better understood in bitches, few studies have addressed the molecular factors involved in feline pyometra. Therefore, this review aims to provide an up-to-date and comprehensive discussion of pyometra in cats, focusing on the regulation of molecular factors described in this species, including hormonal, redox, immunological, and growth factors. Understanding the regulation of these factors in pyometra is crucial for elucidating its pathogenesis in domestic cats and for improving diagnosis and identifying novel therapeutic approaches.

Keywords: feline pyometra; hormonal disorders; molecular factors; uterine infection.

Figure 1

Schematic representation of the domestic cat estrous cycle and pyometra development. (a) Reproductive cycle of cats. The cycle begins with proestrus, followed by estrus, characterized by male receptivity and elevated E2 levels. Without ovulatory stimulus or spontaneous ovulation (1), cats return to proestrus, potentially experiencing brief interestrus or anestrus periods. In ovulatory cycles (2 and 3), fertilization may occur, resulting in pregnancy (2), lasting 63–65 days; without fertilization (3), cats enter diestrus, a luteal phase. Post-pregnancy and lactation, or after diestrus, cats return to proestrus through interestrus intervals or seasonal anestrus. (b) Hormonal factors favoring bacterial proliferation and pyometra development. During proestrus and estrus, increased E2 causes uterine sensitization and cervical opening, while in diestrus, increased P4 results in uterine relaxation, increased glandular secretion, anti-inflammatory action, and cervical closure. (c) Photomicrographs of uterus with grade 3 pyometra. Lower magnification: uterine cross-section showing glandular hyperplasia and ectasia (arrows) and interstitial inflammatory infiltrate (arrowhead) with pus accumulation in the uterine lumen (asterisk). Higher magnification (inset): glandular (asterisk) and interstitial (arrow) infiltration of neutrophils, lymphocytes, and macrophages. E2, estradiol; P4, progesterone; scale bar = 100 μm.

Figure 2

Plasma and uterine modulation of molecular factors involved in the occurrence of pyometra in domestic cats. P4, progesterone; PR, progesterone receptor; ERα, estrogen receptor α; Kiss1, kisspeptin; kiss1r, kisspeptin receptor; VEGF, vascular endothelial growth factor; flk-1, tyrosine kinase receptor 1; PLGF, placental growth factor; CRP, C-reactive protein; SAA, serum amyloid A protein; IL-6, interleukin 6; MIF, macrophage migration inhibitory factor; IL-10, interleukin 10; MDA, malondialdehyde; 8-OHdG, 8-hydroxy-2′-deoxyguanosine; SOD, superoxide dismutase; CAT, catalase; GPx, glutathione peroxidase; TAC, total antioxidant capacity; FRAP, ferric reducing ability of plasma; CUPRAC, cupric reducing antioxidant capacity; TEAC, trolox equivalent antioxidant capacity. Upward arrows (↑) indicate an increase in expression or activity of the respective factors, while downward arrows (↓) indicate a decrease.