Expression and regulation of tumor necrosis factor (TNF) and TNF‐receptor family members in the macaque corpus luteum during the menstrual cycle

Abstract

Members of the tumor necrosis factor (TNF)-receptor (R) family may be involved in the tissue remodeling that occurs in the primate corpus luteum (CL) during development and regression. As a first step towards addressing this issue, studies assessed TNF ligand-R expression and regulation in CL collected from monkeys during the early (ECL, d3–5), mid (MCL, d7–8), mid-late (MLCL, d10–11), late (LCL, d14–16), and very late (VLCL, menses) luteal phase of the menstrual cycle. CL were also collected after gonadotropin and/or steroid ablation and replacement (with hLH and the progestin R5020) for 3 days at mid-late luteal phase. TNF-α, -β, FAS ligand (FASL), and TNF-R1 mRNA levels were 2- to 6-fold greater (p<0.05) at the MLCL or LCL phase as compared to earlier (ECL, MCL). In contrast, TNF-R2 and FAS mRNA levels did not change during the luteal phase. Immunohistochemical staining for TNF-β, TNF-R1, TNF-R2, FAS, and FASL was observed in luteal cells, whereas only TNF-β staining was observed in endothelial cells. Several TNF-R components were influenced by LH and/or steroid ablation; notably, steroid ablation reduced (p<0.05) luteal TNF-α, but not TNF-β, mRNA levels, which was prevented by progestin treatment. In contrast, steroid ablation increased (p<0.05) luteal cell immunostaining for FAS and FASL, which was reduced by progestin treatment. Thus, several members of the TNF R-ligand family are expressed in the primate CL in an LH- and/or progestin-dependent manner. Peak expression in the late luteal phase may signify a role for the TNF-R system in death receptor-mediated apoptosis during luteolysis.

Apoptosis-Related Factors in the Luteal Phase of the Domestic Cat and Their Involvement in the Persistence of Corpora Lutea in Lynx

“…In this study, luteal cells of the domestic cat, while presenting high receptivity to TNF via expression of TNFRSF1A and TNFRSF1B , were not identified as a source of this cytokine, in contrast to other species [ 43 , 53 , 68 ]. The feline TNF may be derived from other sources, such as immune and endothelial cells [ 43 ].…”

“…While TNFRSF1A contains the death domain and can transduce the death signal, in contrast, TNFRSF1B does not possess the death domain and can act as a pro-survival factor [ 40 , 48 , 49 ]. Presented list of factors was found to play an important role throughout the luteal phase of many species, including representatives of rodents, cattle and primates [ 42 , 48 – 53 ]. Both intrinsic and extrinsic pathways lead to activation of the caspase family, i .…”

The Interface of the Immune and Reproductive Systems in the Ovary: Lessons Learned from the Corpus Luteum of Domestic Animal Models

“…Also similar to the cow, the combination of TNFA and IFNG exert profound proapoptotic effects on rodent luteal cells 92,93 and alter the Fas/FasL system 43,94 . In macaque CL, TNF mRNA increases with age of the CL, 95 and human luteal cells collected during the late luteal phase secrete greater concentrations of TNF in vitro than cells from the early luteal phase 96 . Further, luteolytic effects of TNF and IFNG on human and non‐human primate luteal cells also appear to involve Fas/FasL.…”

Localization of gene and protein expressions of tumor necrosis factor-α and tumor necrosis factor receptor types I and II in the bovine corpus luteum during the estrous cycle1

“…The TNF-RII was found in the granulosa cells of porcine ovary (Nakayama et al, 2003) and the CL in rats (Abdo et al, 2008) and primates (Peluffo et al, 2009). The TNF-RII mRNA expression was greatest in the CL of the re- gressed stage in this study.…”