Expression of TGF beta in the placental bed is not altered in sporadic miscarriage

Extravillous trophoblast invasion of uterine stroma and spiral arteries (SA) is essential for normal pregnancy and is reduced in preeclampsia and late miscarriage. The control mechanisms are not understood, but transforming growth factor-beta (TGF-beta) may be a candidate. Placental and placental bed biopsies were obtained from early (8(+0)-12(+6) weeks) euploid miscarriages (n = 10), early aneuploid miscarriages (n = 10), late (13(+0)-19(+6) weeks) euploid miscarriages (n = 10) and controls of the same gestation (n = 20). Frozen sections were immunostained for TGF-beta1, 2 and 3. Immunoreactivity of trophoblast and uterine cell populations was assessed semi-quantitatively. TGF-beta1 immunolocalization was limited to extracellular matrix in cytotrophoblast islands and cytotrophoblast shell, perivascular fibrinoid and interstitial trophoblast and did not differ in miscarriage compared with controls. TGF-beta2 was expressed additionally in endovascular trophoblast and multinucleate trophoblast giant cells. There was no aberrant TGF-beta2 immunolocalization in late miscarriage, but TGF-beta2 immunoreactivity was increased in extracellular matrix in cytotrophoblast islands in early miscarriage. TGF-beta3 was absent from all cell populations. Stromal and extravillous trophoblast TGF-beta2 immunolocalization suggests a more important role in trophoblast invasion than TGF-beta1, but neither isoform was altered in miscarriage. Altered TGF-beta localization is therefore unlikely to play a role in abnormal trophoblast invasion and SA transformation in miscarriage.