Modulation of Bovine Endometrial Cell Receptors and Signaling Pathways as a Nanotherapeutic Exploration against Dairy Cow Postpartum Endometritis

SIMPLE SUMMARY: The provision of updated information on the molecular pathogenesis of bovine endometritis with host-pathogen interactions and the possibility of exploring the cellular sensors mechanism in a nanotechnology-based drug delivery system against persistent endometritis were reported in this review. The mechanism of Gram-negative bacteria and their ligands has been vividly explored, with the paucity of research detail on Gram-positive bacteria in bovine endometritis. The function of cell receptors, biomolecules proteins, and sensors were reportedly essential in transferring signals into cell signaling pathways to induce immuno-inflammatory responses by elevating pro-inflammatory cytokines. Therefore, understanding endometrial cellular components and signaling mechanisms across pathogenesis are essential for nanotherapeutic exploration against bovine endometritis. The nanotherapeutic discovery that could inhibit infectious signals at the various cell receptors and signal transduction levels, interfering with transcription factors activation and pro-inflammatory cytokines and gene expression, significantly halts endometritis. ABSTRACT: In order to control and prevent bovine endometritis, there is a need to understand the molecular pathogenesis of the infectious disease. Bovine endometrium is usually invaded by a massive mobilization of microorganisms, especially bacteria, during postpartum dairy cows. Several reports have implicated the Gram-negative bacteria in the pathogenesis of bovine endometritis, with information dearth on the potentials of Gram-positive bacteria and their endotoxins. The invasive bacteria and their ligands pass through cellular receptors such as TLRs, NLRs, and biomolecular proteins of cells activate the specific receptors, which spontaneously stimulates cellular signaling pathways like MAPK, NF-kB and sequentially triggers upregulation of pro-inflammatory cytokines. The cascade of inflammatory induction involves a dual signaling pathway; the transcription factor NF-κB is released from its inhibitory molecule and can bind to various inflammatory genes promoter. The MAPK pathways are concomitantly activated, leading to specific phosphorylation of the NF-κB. The provision of detailed information on the molecular pathomechanism of bovine endometritis with the interaction between host endometrial cells and invasive bacteria in this review would widen the gap of exploring the potential of receptors and signal transduction pathways in nanotechnology-based drug delivery system. The nanotherapeutic discovery of endometrial cell receptors, signal transduction pathway, and cell biomolecules inhibitors could be developed for strategic inhibition of infectious signals at the various cell receptors and signal transduction levels, interfering on transcription factors activation and pro-inflammatory cytokines and genes expression, which may significantly protect endometrium against postpartum microbial invasion.