Reproduction Abstracts

Transforming growth factor beta (TGFβ) can induce The Warburg-effect, or aerobic glycolysis, in tumorigenesis. Energy-rich lactate, a by-product of glycolysis, ‘feeds’ tumour cells and increases apoptosis resistance, angiogenesis, and invasion, fuelling tumour progression and metastasis. As TGFβ is increased in the peritoneal fluid of women with endometriosis, we asked, is there a Warburg-like effect at play in endometriosis.

Peritoneal fluid (PF) (n=16), peritoneal mesothelial cells (PMC) (n=6), peritoneum, endometriosis lesions, and endometrium biopsies were collected from women with/without endometriosis. TGFβ1 and lactate were assayed in PF. Glycolic-pathway enzyme expression in tissue biopsies was determined by qRT-PCR and immunohistochemistry. PMC were exposed to physiological concentrations of TGFβ1.

TGFβ1, HIF1α and its target genes; LDHA and PDK1 were significantly increased in ectopic compared to eutopic endometrium (P<0.05). Peritoneum adjacent to endometriosis lesions expressed significantly higher levels of TGFβ1, HIF1α, and GLUT1 (P<0.05) and these proteins were localized to the PMC. PF of women with endometriosis had significantly higher TGFβ1 (P<0.05) and lactate (P<0.05) (positive correlation). Exposure of PMC to TGFβ1 increased lactate levels (P<0.05) and HIF1α protein. GLUT1 LDHA and PDK1 were all significantly increased on exposure to TGFβ1 in PMC (P<0.05).

We have shown that ectopic endometrium may have an altered metabolism induced by TGFβ1 which may explain endometriosis lesion development. Increasing lactate within the PF and by ajacent peritoneum may ‘feed’ lesions, establishing an integrated endometrosis niche. Therapies which inhibit glycolosis may provide potential treatments for endometriosis.