Differential effects of catecholamines on vascular rings from ductus venosus and intrahepatic veins of fetal sheep.

Ductus venosus (DV) sparing means the maintenance of blood flow through the DV following reduction of liver venous blood supply during fetal hypoxia. The present study compared the reactions of the isthmic portion of the DV and intrahepatic veins (IHVs) to catecholamines in vitro. Vessel rings of 1 mm width and 3 mm diameter were obtained from 17 fetal sheep (88-136 days gestational age, median 120 days). The immunohistochemical examination of the DV and IHV was performed in eight cases using an antibody against alpha-smooth muscle actin and an antibody against alpha-adrenergic receptors. Five vessel rings of the DV in early gestation (median 95 days) did not respond to KCl-induced depolarisation. Force development in response to KCl of both vessel types increased with gestational age (P < 0.05). The IHV required 4.1 +/- 0.8 min (mean +/- S.E.M.) and the DV 14.5 +/- 4.0 min to reach the maximum tension in response to KCl, which was 5.0 +/- 4.0 mN in the IHV and 2.2 +/- 1.9 mN in the DV (n = 12, P < 0.05). The maximum forces developed in response to noradrenaline (norepinephrine; 42 microM, n = 9) and adrenaline (epinephrine; 100 microM, n = 12) were about sixfold higher in the IHV rings than in the DV rings (P < 0.05). The EC50 values of the DV and the IHV rings to noradrenaline were 5.9 +/- 1.3 microM and 5.0 +/- 1.3 microM, respectively (P = 0.03). The EC50 values of the adrenaline responses were 2.5 +/- 0.5 microM for the DV and 2.2 +/- 0.7 microM for the IHV (not significant). The alpha-adrenergic receptors were present in the well-structured media of IHVs, but were less distinctive in the wall of the DV. DV sparing can be attributed to an increased resistance of IHVs to catecholamines compared with the DV. The different responses can be explained by different anatomical and functional properties of the two vessel types.

Invasive depth of extravillous trophoblast correlates with cellular phenotype: a comparison of intra- and extrauterine implantation sites.

During intrauterine human placentation, extravillous trophoblast invades uterine tissues starting with proliferating stem cells at the basement membrane of anchoring villi. Transition to the postproliferative invasive phenotype takes place several cell layers distant. Here we show that in intrauterine pregnancies invasive trophoblast comprises three cellular phenotypes: a. Small spindle-shaped trophoblast cells are found along the whole invasive pathway throughout pregnancy. They are embedded in little heterogeneous extracellular matrix but expose only fibronectin receptors (integrins alpha5beta1, alphavbeta3/5), resulting in a partial integrin-matrix mismatch. b. Large polygonal trophoblast cells are rare in early pregnancy but increase in number towards term. They secrete ample heterogeneous extracellular matrix and expose integrins specifically matching the opposing matrix molecules (integrins alpha6beta4, alpha5beta1). c. Multinucleated giant cells in all stages of pregnancy form a kind of peripheral shell of trophoblast. In contrast to intrauterine pregnancies, in viable tubal pregnancies, Mib-1 expression indicating proliferation, extends deeply into the invasive pathway. Trophoblast cells of the invasive pathway mostly belong to the small spindle-shaped phenotype and secrete little extracellular matrix, mainly fibronectins. At the transition to the second cellular layer of cell columns expression of integrin alpha6beta4 switches to expression of alpha5beta1 and alphavbeta3/5. Viable tubal pregnancies are characterised by a broad overlap of proliferative with invasive phenotype as well as a general integrin-matrix mismatch. The differences in proliferation patterns, cellular phenotype and matrix-integrin co-localisation may well explain the increase of invasiveness of normal extravillous trophoblast from term intrauterine via early intrauterine to viable tubal pregnancies.