The NF-κB pathway in human endometrium and first trimester decidua

Abstract

Nuclear factor kappa B (NF-κB) regulates proinflammatory genes and may be involved in inflammation associated with reproductive events e.g. menstruation, implantation. Activation of NF-κB involves several protein kinases and subsequent degradation of an endogenous inhibitor, IκBα. This study details expression of NF-κB pathway intermediates in human endometrium and first trimester decidua. Messenger RNA was detected for IκBα, and IκB kinase γ (IKKγ, a scaffolding protein) and the protein kinases, IKKα, IKKβ, NF-κB inducing kinase (NIK), mitogen-activated protein kinase Erk kinase kinase 1 (MEKK1) and TANK-binding kinase 1 (TBK1) using real-time quantitative polymerase chain reaction (PCR). IκBα and TBK1 mRNA were increased in the perimenstrual phase of the menstrual cycle. This suggests that there is activation of NF-κB due to premenstrual progesterone withdrawal, since NF-κB activity increases IκBα gene expression. Differential expression of NF-κB pathway intermediates occurred when progesterone concentrations increased in early pregnancy; IKKα and NIK mRNA levels increased in decidua whilst IKKβ and MEKK1 mRNA levels declined. Expression profiles of IKKα and NIK proteins were determined immunohistochemically. Both were detected in glandular epithelium and endothelium of endometrium. In decidua, both were present in epithelium and decidualized stromal cells. The results of this study suggest that NF-κB is activated during menstruation. During early pregnancy, NF-κB may also be activated (via IKKα-NIK) and may regulate the expression of molecules vital for implantation and successful pregnancy. However, pro-inflammatory signalling to NF-κB (via IKKβ-MEKK1) may be down-regulated in early pregnancy, contributing to the immunosuppressive mechanisms which prevail at this time.