Nuclear factor-kappa-B-inhibitor alpha (NFKBIA) is a developmental marker of NF-κB/p65 activation during in vitro oocyte maturation and early embryogenesis

BACKGROUND: The oocyte-to-embryo transition (OET) requires a co-ordinated transcriptional programme acting through evolutionarily conserved events, and transcription factors (TFs) are known to control these processes. Here, we focus on nuclear factor (NF)-kappa B, a TF involved in several cellular processes, studying NF kappa B-inhibitor (NFKBIA) mRNA and its protein product, I kappa B alpha, during OET. NFKBIA and IkBa are part of a regulatory loop, as IkBa is the major down-regulator of NF-kappa B activation while NFKBIA transcription is activated by NF-kappa B. METHODS AND RESULTS: We found a dynamic correlation between NFKBIA transcript, expression of I kappa B alpha-protein and activation of NF-kappa B/p65 in bovine oocyte and embryo. During the transition from immature to in vitro matured bovine oocyte, we observed a decrease in maternal NFKBIA mRNA and a parallel increase of the I kappa B alpha-protein (both P < 0.05). In the embryo, NFKBIA neo-synthesis is activated as a consequence of embryo genome activation (EGA), and IkBa decreases. NF-kappa B/p65-binding activity was detectable at low levels in immature oocyte, disappeared in dormant metaphase II oocyte and was strong in the embryo, during embryonic NFKBIA synthesis. The level of NF-kappa B/p65 DNA binding correlates with the timing of meiotic silencing during bovine oocyte maturation and embryonic transcription reprogramming. CONCLUSIONS: The I kappa B alpha/NF-kappa B circuit appears to be a tightly stage-controlled mechanism that could govern OET, being activated at EGA. Our findings represent the first characterization of NFKBIA and IkBa as maternal effectors in both the bovine oocyte and embryo. We suggest a role for NFKBIA as a marker of NF-kappa B/p65 activation in the human oocyte and early embryo.