Tumor Necrosis Factor-alpha as a possible auto-/paracrine factor affecting estrous cycle in the cat uterus

Abstract

Tumor Necrosis Factor-alpha (TNFα) is a pleiotrophic cytokine, affects either normal or tumor cells, and influences cellular differentiation. TNFα role in female reproduction has been proven to be mediated through an influence on prostaglandin (PGs) synthesis and output. To evaluate the possible role of TNFα in an auto-/paracrine regulation in the cat uterus, mRNA expression coding for TNFα and its receptors (TNFR1 and TNFR2), and TNFα protein content at different stages of the estrous cycle were investigated. Additionally, TNFα involvement in PG secretion at different stages of the estrous cycle was investigated by in vitro tissue culture. Gene expressions coding for TNFα and TNFR1 were the highest at diestrus (P < 0.05). TNFα protein expression was the lowest at interestrus (P < 0.05). Nevertheless, TNFR2 was not affected by the estrous stage. TNFα at a dose of 1 ng/ml significantly increased PGF 2α secretion at estrus (P < 0.01) and PGE 2 secretion at diestrus (P < 0.001) after 12h incubation. Overall findings indicate that TNFα locally produced in the cat's uterus, stimulates PG secretion in an estrous cycle-related manner.

LPS-Challenged TNFαProduction, Prostaglandin Secretion, and TNFα/TNFRs Expression in the Endometrium of Domestic Cats in Estrus or Diestrus, and in Cats with Pyometra or Receiving Medroxyprogesterone Acetate

“…In our previous study, we showed that isolated fragments of feline uteri produce PGs after supplementation of the culture media with TNF α [19]; similar results were shown with endometrium of the cow [29], pig [30], horse [31], and human [32]. Prostaglandins are synthesized from AA by an enzymatic cascade and regulate a variety of processes in reproduction and immune function [33].…”

“…In the present study, TNF α seemed to be more weakly expressed in the luteal phase endometrium compared with follicular phase endometrium, which is not exactly identical with our previous observations made with whole uterine fragments. In that study, uterine TNF α protein expression and mRNA transcription did not differ between cats in the follicular or luteal phases [19]. This discrepancy may be due to different methods used for TNF α analysis.…”

“…In the human endometrium, TNF α is synthesized by immune-competent cells, such as macrophages or monocytes, as well as by endometrial fibroblasts [17] and glandular epithelial cells [18]. We showed recently that TNF α is produced in the feline endometrium in a cycle-dependent manner and is responsible for augmentation of prostaglandin secretion [19]. Otto and Rawlings [20] observed that supernatants of peritoneal exudate cells from cats produced vast amounts of TNF α when exposed to LPS.…”

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

“…Studies have shown that interferon-gamma (INFγ), macrophage migration inhibitory factor (MIF), tumor necrosis factor-alpha (TNFα), and interleukin 10 (IL-10) have higher expressions in the uterus of cats in the proestrus/estrus and diestrus than in the anestrus, while INFγ and MIF have a higher gene expression in the proestrus/estrus and diestrus phases, respectively [14] (Table 2). Jursza et al [28] also demonstrated that TNFa has higher endometrial expression in cats in the estrus, while Siemieniuch et al [154] described lower gene and protein expressions of TNF in the interestrus. In this study, TNFα receptors (TNFR1 and TNFR2) were expressed in the uterus of the female cat, with TNFR1 showing greater gene expression in the diestrus and TNFR2 showing no differences between the phases of the cycle [154].…”

“…Jursza et al [28] also demonstrated that TNFa has higher endometrial expression in cats in the estrus, while Siemieniuch et al [154] described lower gene and protein expressions of TNF in the interestrus. In this study, TNFα receptors (TNFR1 and TNFR2) were expressed in the uterus of the female cat, with TNFR1 showing greater gene expression in the diestrus and TNFR2 showing no differences between the phases of the cycle [154].…”