Endometritis
Endometritis is a chronic inflammatory disorder of the uterine lining driven by dysregulated innate immunity and bacterial infections (e.g., E. coli, Chlamydia). Protheragen provides MyD88-focused drug discovery services to disrupt inflammatory pathways in endometritis, including TLR/IL-1R-MyD88 hyperactivation, neutrophil/macrophage infiltration, and TGF-β1-mediated fibrotic remodeling.
Introduction to Endometritis
The incidence of endometritis among reproductive aged women stands at 10–15% and is reported to be higher among patients with recurrent pelvic infections and postpartum complications. Chronic endometritis contributes to infertility, recurrent pregnancy loss, and chronic pelvic pain. Other studies have pointed towards TLR4/MyD88/NF-κB signaling as a pivotal role in sustaining inflammation, abnormal cytokine secretion such as IL-1β, IL-6, and TNF-α, and fibroblast cell activation responsible for endometrial scarring.
Pathogenesis of Endometritis
- TLR Activation: PAMPs and DAMPs binding to TLR4 trigger myddosome formation that activates MyD88 dependent NF-κB and MAPK signaling cascades.
- Cytokine Storm: Signaling through MyD88 leads to upregulation of pro inflammatory cytokines like IL-1β, IL-6 along with chemokine CXCL8 that drives largely neutrophilic and macrophagic infiltration.
- Fibrotic Remodeling: Sustained inflammation leads to activation of myofibroblasts through TGF-β1 signaling and collagen deposition to the tissue, which diminishes endometrial receptivity.
Fig.1 Illustration of DHT alleviates inflammatory response via AR mediated TLR4/MYD88 signaling pathway in bEECs induced by LPS. (Liang et al., 2023)MyD88-Targeted Therapeutic Development for Endometritis
| Therapeutic Strategy | Mechanism of Action | Progress & Challenges | Development Stage |
| miR-30a Agonism | Targets MyD88 mRNA 3'-UTR to inhibit MyD88/Nox2/ROS/NF-κB signaling, reducing IL-1β and IL-6. | miR-30a agomirs (chemically synthesized mimics) to upregulate miR-30a in endometrial cells. | Preclinical |
| Engeletin (Flavanonol Glycoside) | Inhibits TLR4-MyD88 signaling, blocking downstream IRAK1/TRAF6/TAK1 and NF-κB activation. | Engeletin oral or intrauterine administration to suppress TNF-α, IL-1β, and COX-2. | Preclinical |
| Dihydrotestosterone (DHT) Supplementation | Binds androgen receptor (AR) to suppress TLR4/MyD88 signaling, reducing TNF-α, IL-1β, and IL-6. | DHT therapy with AR-dependent modulation of MyD88 expression in bovine endometrial cells. | Preclinical |
Disclaimer: Protheragen focuses on providing preclinical research services. This table is for information exchange purposes only. This table is not a treatment plan recommendation. For guidance on treatment options, please visit a regular hospital.
Our Services
Protheragen's services include MyD88-targeted therapeutic discovery and advanced disease models development for Endometritis. Our platform integrates uterine-specific in vitro and in vivo models for high-throughput screening of MyD88 signaling modulators, TLR/IL-1R-driven endometrial immune activation, and fibrosis pathways.
Therapeutic Discovery Platform for Endometritis
Protheragen's MyD88 discovery platform for endometritis leverages immune-endometrial crosstalk models to rebalance dysregulated innate and adaptive immune interactions. The platform accelerates preclinical validation by targeting MyD88-dependent cytokine networksand fibrotic remodeling through novel inhibitors, degraders, or biologics, while synergizing with existing anti-inflammatory therapies.
Disease Models Development for Endometritis
Protheragen provides a complete set of preclinical models for Endometritis, including cell-based models, organoid models, and animal models that recapitulate the multifactorial pathophysiology of this immune-mediated uterine disorder.
- Primary Human Endometrial Epithelial Cells
- Macrophage-Endometrial Co-Cultures
- 3D Endometrial Organoids
- Fibroblast Models
- LPS-Induced Acute Endometritis Mice
- Chronic Pelvic Infection Models
- Fibrosis-Focused Transgenic Mice
- Humanized Endometrial Injury Models
Protheragen delivers end-to-end solutions for MyD88-related diseases, integrating disease model development, pharmacokinetics and drug safety evaluation. Other focuses include investigator-initiated trials aimed to accelerate preclinical-to-clinical translation.
If you are interested in our services, please don't hesitate to contact us.
References
- Jiang, K., et al. "Therapeutic Role of Mir-30a in Lipoteichoic Acid-Induced Endometritis Via Targeting the Myd88/Nox2/Ros Signaling." Oxid Med Cell Longev 2021 (2021): 5042048.
- Liang, Y., et al. "Dihydrotestosterone Mediates the Inflammation Effect under Lipopolysaccharides in Bovine Endometrial Epithelial Cells Via Ar Blockading Tlr4/Myd88 Signaling Pathway." Anim Reprod Sci 255 (2023): 107292.
All of our services and products are intended for preclinical research use only and cannot be used to diagnose, treat or manage patients.