Equine endometrial fibrosis correlates with 11β-HSD2, TGF-β1 and ACE activities

Endometrial periglandular fibrosis (EPF) contributes to embryonic and fetal loss in mares. Equine EPF correlates inversely with conception and successful gestation. In the modified Kenney endometrial biopsy classification system, EPF categories I, IIA, IIB, and III correspond to minimal, mild, moderate, and severe fibrosis (±inflammation), respectively. Paraffin sections of biopsy specimens were stained with H&E, and picrosirius red (specific for fibrillar collagens types I and III), to determine %EPCVF. Endometrial ACE-binding activity, TGF-β1 and 11β-HSD2 activities were also measured. Ultrastructural changes in EPF categories IIB and III endometria strongly suggested myofibroblastic transformation. ACE-binding activity was highest in EPF category IIB; however, endometrial TGF-β1 and 11β-HSD2 activities were significantly correlated to the severity of EPF (P < 0.05). We conclude that, locally generated angiotensin II initiates the expression of TGF-β1 resulting in myofibroblastic transformation. 11β-HSD2 in concert appears to modulate the severity of endometrial fibrosis.