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

Nuclear factor kappa B (NF-kappaB) regulates proinflammatory genes and may be involved in inflammation associated with reproductive events e,g. menstruation, implantation. Activation of NF-kappaB involves several protein kinases and subsequent degradation of an endogenous inhibitor, I kappaB alpha, This study details expression of NF-kappaB pathway intermediates in human endometrium and first trimester decidua, Messenger RNA was detected for I kappaB alpha, and I kappaB kinase gamma (IKK gamma, a scaffolding protein) and the protein kinases, IKK alpha, IKK beta, NF-kappaB inducing kinase (NIK), mitogenactivated protein kinase Erk kinase kinase 1 (MEKK1) and TANK-binding kinase 1 (TBK1) using real-time quantitative polymerase chain reaction (PCR), I kappaB alpha and TBK1 mRNA were increased in the perimenstrual phase of the menstrual cycle, This suggests that there is activation of NF-kappaB due to premenstrual progesterone withdrawal, since NF-kappaB activity increases I kappaB alpha gene expression. Differential expression of NF-kappaB pathway intermediates occurred when progesterone concentrations increased in early pregnancy; IKK alpha and NIK mRNA levels increased in decidua whilst IKK beta and MEKK1 mRNA levels declined. Expression profiles of IKK alpha 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-kappaB is activated during menstruation. During early pregnancy, NF-kappaB may also be activated (via IKK alpha -NIK) and may regulate the expression of molecules vital for implantation and successful pregnancy. However, proinflammatory signalling to NF-kappaB (via IKK beta -MEKK1) may be down-regulated in early pregnancy, contributing to the immunosuppressive mechanisms which prevail at this time.