VEGF, its receptors and the Tie receptors in recurrent miscarriage

The aetiology of recurrent miscarriage (at least three consecutive miscarri ages) usually remains unsolved, The vascular endothelial growth factor (VEG F) family of proteins, together with their receptors and the Tie (tyrosine kinase with immunoglobulin and epidermal growth factor homology domains) re ceptors, are crucial for embryonic development. Therefore, we used immunohi stochemistry to analyse the expression of VEGF, the VEGF receptors (VEGFR)- 1, -2, and -3, and the Tie-1 and Tie-2 receptors in placental and decidual tissue of women with a history of recurrent miscarriage and missed abortion (MA; n = 12) or blighted ovum (BO; n = 6), and from normal early terminate d pregnancies (n = 12). Compared with controls, the MA and BO groups showed : (i) diminished placental trophoblastic VEGF immunoreactivity; (ii) weaker VEGFR-1 and -2 immunoreactivity in decidual vascular endothelium; (iii) re duced placental trophoblastic Tie-1 receptor immunoreactivity; and (iv) red uced decidual vascular endothelial Tie-1 and -2 receptor immunoreactivity. The absence of VEGFR-3 immunoreactivity in decidual vascular endothelium wa s also noted in all study groups. Interestingly, placental villi from the B O group presented blood vessel-like structures negative for von Willebrand factor, but positive for VEGF. VEGFR-1, -2, -3, Tie-1 and Tie-2 receptor. W e conclude that the expression of these antigens may be altered in recurren t miscarriages.