Toll-Like Receptor 9 expression during Mouse Preimplantation Development

In mammals, the innate immune system plays essential roles in maintaining homeostasis through numerous pathways involving Tolllike receptor (TLR) signaling. Pathogen recognition occurs during the first step of innate immunity, which is triggered by the sensing of pattern recognition receptors (PRRs) derived from pathogens. The TLR molecules are flagship members of this system and counteract pathogenic infections in host animals. In mice, the TLR family consists of 12 members (TLR1–9 and TLR11–13). Each member recognizes specific molecular components derived from pathogens. After pathogen recognition, TLRs stimulate downstream signaling pathways to induce type I interferon-α/β (IFN-α/β) and inflammatory cytokine secretion. During mammalian post implantation development, TLRs are expressed in both embryonic and placental tissues in mid and late pregnancy.

In preimplantation development, TLR members were expressed in the cell surfaces in embryos from the 2-cell to blastocyst stages, of which TLR2 and TLR4 were localized mainly in the trophectoderm (TE) of blastocyst. The first differentiation occurs at the blastocyst stage into 2 types of cell lineage: inner cell mass (ICM) and TE. The former mainly generates embryo proper; on the other hand, the latter gives rise to extra embryonic tissue such as placenta. In addition, TE cell-derived trophoblast stem cells (TSCs) expressed Tlr1–6 mRNA but not Tlr9, and also expressed antiviral genes including IFN-β by TLR3 agonist stimuli.

This indicates that TE and TSCs are potent to show antipathogenic responses. On the other hand, certain types of TLRs expressed in embryonic stem cells (ESCs) could not activate downstream signaling pathways to IFN-α/β. Therefore, TLRs appear to show cell type-specific characteristics in ESCs and TSCs. However, there is not enough knowledge about pathogen sensor TLR9 in oocytes and early embryos in mammals.