Endometrial Epithelial Lactate Deficiency Drives CD8+ T-Cells Dysregulation in Unexplained Recurrent Implantation Failure - PubMed
3 hours ago
- #CD8+ T-cells
- #endometrial glycolysis
- #recurrent implantation failure
- Unexplained recurrent implantation failure (RIF) is linked to abnormal endometrial conditions, but its exact cause remains unknown.
- Single-cell RNA sequencing revealed increased proliferation and activation of cytotoxic CD8+ T-cells in the endometria of RIF patients, hindering embryo implantation.
- The glandular epithelium in RIF patients showed abnormal glycolysis and reduced lactate production, affecting key metabolic genes (SLC2A1, ALDOA, LDHA, SLC16A3).
- Mouse experiments demonstrated that inhibiting endometrial lactate production prevents embryo implantation, which can be reversed by lactate supplementation.
- Lactate inhibition did not affect implantation in CD8+ T-cell-depleted mice, suggesting lactate's role in regulating CD8+ T-cell activity.
- In vitro studies confirmed that lactate inhibition impacts CD8+ T-cell proliferation and activation.
- The study proposes that unexplained RIF involves disrupted immune balance due to impaired glycolysis and lactate production in the glandular epithelium.