RIS ID

36935

Publication Details

Ilad, R. S., Fleming, S. D., Murphy, C. R. & Fazleabas, A. T. (2010). Immunohistochemical study of the ubiquitin-nuclear factor-κB pathway in the endometrium of the baboon (papio anubis) with and without endometriosis. Reproduction Fertility And Development, 22 (7), 1118-1130.

Abstract

The aim of the present study was to conduct a semiquantitative immunohistochemical investigation into the levels of intermediary proteins within the nuclear factor (NF)-kappa B pathway throughout the menstrual cycle in a non-human primate, namely the baboon (Papio anubis), with and without endometriosis. Formalin-fixed eutopic (n = 2-4) and ectopic (n = 6-7) endometrial tissues from baboons at the mid-luteal phase were embedded in paraffin and examined for NF-kappa B pathway components (i.e. I kappa B kinase (IKK) alpha, IKK beta, phosphorylated (phospho-) I kappa B alpha and phospho-NF-kappa B p65 subunit), ubiquitin, 19S proteasome and the NF-kappa B activator tumour necrosis factor (TNF)-alpha. Similarly, endometrial tissues from baboons at the late follicular, mid-luteal and menses phase (n 2-4) were investigated to determine the levels of these proteins throughout the menstrual cycle. Cytoplasmic stromal IKK alpha and glandular 19S proteasome immunostaining was elevated in the ectopic endometrium, whereas levels of ubiquitin, phospho-p65, IKK beta, TNF-alpha and nuclear 19S proteasome were similar in the eutopic and ectopic endometrium. A significant decrease in phospho-I kappa B alpha nuclear immunostaining was observed within glandular cells of the ectopic endometrium. In the eutopic endometrium, IKK alpha, ubiquitin and 19S proteasome immunostaining was elevated in different phases of the menstrual cycle, whereas levels of phospho-p65, IKK beta, phospho-I kappa B alpha and TNF-alpha remained unchanged. We have demonstrated that, in the baboon endometriosis model, levels of IKK alpha immunostaining are elevated, whereas those of phospho-I kappa B alpha are reduced, consistent with the hypothesis that excessive NF-kappa B activity plays a role in reducing ectopic endometrial apoptosis, which contributes to the pathophysiology of endometriosis. Further studies are required to confirm a causal association between elevated IKK alpha levels and reduced endometrial apoptosis.

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Link to publisher version (DOI)

http://dx.doi.org/10.1071/RD08086