Immunohistochemical study of the ubiquitin - nuclear factor-ΚB pathway in the endometrium of the baboon (Papio anubis) with and without endometriosis

Author:

Ilad Romina S.,Fleming Steven D.,Murphy Christopher R.,Fazleabas Asgerally T.

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)-κB 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-κB pathway components (i.e. IκB kinase (IKK) α, IKKβ, phosphorylated (phospho-) IκBα and phospho-NF-κB p65 subunit), ubiquitin, 19S proteasome and the NF-κB activator tumour necrosis factor (TNF)-α. 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 IKKα and glandular 19S proteasome immunostaining was elevated in the ectopic endometrium, whereas levels of ubiquitin, phospho-p65, IKKβ, TNF-α and nuclear 19S proteasome were similar in the eutopic and ectopic endometrium. A significant decrease in phospho-IκBα nuclear immunostaining was observed within glandular cells of the ectopic endometrium. In the eutopic endometrium, IKKα, ubiquitin and 19S proteasome immunostaining was elevated in different phases of the menstrual cycle, whereas levels of phospho-p65, IKKβ, phospho-IκBα and TNF-α remained unchanged. We have demonstrated that, in the baboon endometriosis model, levels of IKKα immunostaining are elevated, whereas those of phospho-IκBα are reduced, consistent with the hypothesis that excessive NF-κB 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 IKKα levels and reduced endometrial apoptosis.

Publisher

CSIRO Publishing

Subject

Developmental Biology,Endocrinology,Genetics,Molecular Biology,Animal Science and Zoology,Reproductive Medicine,Biotechnology

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1. The Known, the Unknown and the Future of the Pathophysiology of Endometriosis;International Journal of Molecular Sciences;2024-05-27

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3. Cancer driver mutations in endometriosis: Variations on the major theme of fibrogenesis;Reproductive Medicine and Biology;2018-08-16

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