Comparison of the effect of lipopolysaccharide on tumor necrosis factor α (TNF-α) secretion and <i>TNF</i> and <i>TNFR1</i> mRNA levels in feline endometrium throughout the estrous cycle during pyometra and after medroxyprogesterone acetate treatment

Abstract

Endotoxins released by Gram-negative bacteria are potent stimulators of tumor necrosis factor α (TNF-α) production. The objectives of this study were to evaluate plasma levels of TNF-α, TNF-α secretion, and mRNA levels of TNF and TNF-α receptor type 1 (TNFR1) following exposure to lipopolysaccharide (LPS). For this, we used cultured endometrial cells or organ cultures, throughout the estrous cycle, after hormone treatment with medroxyprogesterone acetate (MPA), and during pyometra. Plasma TNF-α concentrations were increased in animals at estrus (P < 0.05) compared to other groups. In the LPS-challenged endometrium, secretion of TNF-α by tissues collected during estrus increased (P < 0.001) compared to that of other groups. LPS, alone or combined with TNF-α, upregulated TNF gene expression in the feline endometrium at diestrus (P < 0.001 for both treatments), in queens treated short-term with MPA (P < 0.01 and P < 0.05, respectively) and in queens treated long-term with MPA (P < 0.01 and P < 0.001, respectively). During pyometra, TNF and TNFR1 mRNA were increased only after tissues were challenged with TNF-α and LPS (P < 0.001 and P < 0.01, respectively). When cultured endometrial cells were challenged with LPS, the concentration of TNF-α increased only in epithelial cells after 4 h and 12 h (P < 0.05 and P < 0.01, respectively). Since LPS did not affect stromal cells, but TNF-α increased its own transcript after 2 h (P < 0.01), 4 h (P < 0.05) and 12 h (P < 0.001), we assume that stromal cells are not directly involved in pathogen recognition, as was the case for epithelial cells.

Molecular Factors Involved in the Reproductive Morphophysiology of Female Domestic Cat (Felis catus)

“…In addition, TNFα and lipopolysaccharide (LPS) increase the in vitro expression of Toll-like receptors (TLRs) 2 and 4 in the endometrial explants of cats in the estrus or those treated with P 4 , thus suggesting the participation of TLRs in pyometra of cats [163], as also demonstrated by Jursza-Piotrowska and Siemieniuch [29]. Activation of these receptors is important for triggering the innate immune response, which is an essential cellular defense mechanism in bacterial infections such as pyometra.…”

“…Studies conducted in the last decade with domestic cats have shown that several growth, hormonal, immunological, and redox factors are expressed differently in the uterus and ovary throughout the reproductive cycle [14,[18][19][20][21][22][23][24][25], as well as in the placenta throughout pregnancy [18,19,26,27]. Moreover, these studies show that changes in the expression of some of these factors are involved in the reproductive alterations observed in pyometra [14,[28][29][30] and in feline immunodeficiency virus (FIV) infection [31][32][33][34]. Thus, this paper reviews the current knowledge about the modulation and expression profiles of hormonal, immunological, redox, and growth mediators in the uterus, ovary, and placenta of domestic cats throughout the estrous cycle and during pregnancy.…”

“…Several hormonal, immunological, redox, and growth mediators are fundamental in the morphophysiology of the female genital system and participate in various processes of the reproductive cycle and pregnancy [58][59][60][61]. Thus, changes in the expression of these mediators have been observed in several pathological conditions in both women and animals, such as recurrent abortion [62,63], preeclampsia [64,65], premature birth [66,67], and pyometra [14,[28][29][30], which can not only result in subfertility or infertility but also cause the death of the individual.…”

Association between Mannheimia haemolytica infection with reproductive physiology and performance in small ruminants: A review

“…Numerous studies have demonstrated that treatment with endotoxin or LPS results in an increase of TNF-α production. Jursza-Piotrowska and Siemieniuch [52] had conducted a study to determine whether the epithelial or the stromal cells are responsible for the release of TNF-α. Their study has shown that the exposure of LPS on feline endometrial cell in vitro significantly increases the release of TNF-α by endometrial epithelial cells, but not the stromal cells.…”