Invasion of extravillous trophoblast cells into the uterus in human pregnancy is tightly regulated. The transforming growth factor-beta (TGFB) family has been suggested to play a role in controlling this process. We hypothesized that TGFB1, 2, and 3 would inhibit the invasive capacity of extravillous trophoblast cells. We also studied trophoblast apoptosis and proliferation and secreted protease levels as potential mechanisms by which these cytokines may act. Inhibition of endogenous TGFB1, 2, and 3 with neutralizing antibodies increased the invasive capacity of extravillous trophoblast cells derived from placental explants. Similarly, addition of exogenous TGFB1, 2, and 3 inhibited the invasive capacity of these cells in a dose-dependent manner. Proliferation of trophoblast in the placental explants did not alter in response to any of the cytokines tested. Apoptosis of villous and extravillous trophoblast did not alter in response to TGFB1, 2, and 3. There was a reduction in secreted levels of matrix metalloproteinase (MMP) 9 and urokinase plasminogen activator in response to all three cytokines. MMP2 and tissue inhibitor of metalloproteinase 1 and 3 levels were not altered. These results suggest that TGFB1, 2, and 3 inhibit trophoblast invasion by a mechanism dependent on reduced protease activity.

uNK cells are a source of IFN-gamma within early human pregnancy decidua. Mechanisms of IFN-gamma inhibition of EVT invasion include both increased EVT apoptosis and reduced levels of active proteases.

Decidual uNK cell supernatants from 12 to 14 weeks gestational age stimulated EVT invasion, potentially by increasing MMP9 levels and reducing apoptosis. Total decidual cell isolates stimulated EVT invasion at both gestational ages investigated, potentially reflecting the complex nature of these cell culture supernatants.

uNK cells from early human pregnancy decidua possess innate protease activity, especially MMP-2, providing further evidence for a role for these cells in regulation of trophoblast invasion and spiral artery remodeling in early placentation.

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Serial changes in serum uric acid concentrations have been studied in a group of healthy women before conception, at regular intervals throughout pregnancy and finally 12 weeks after delivery. Compared with pre-pregnancy values uric acid concentrations decreased significantly by 8 weeks gestation and this reduced level was maintained until about 24 weeks. Thereafter the concentrations increased such that by term they were greater than the pre-pregnancy values in the majority of patients and remained elevated until a t least 12 weeks after delivery. If clinical management during the second half of pregnancy is to be based on increases in serum uric acid concentrations then such increases will have to be carefully interpreted against the background of rising concentrations which occur as part of the physiological response t o normal pregnancy.Modern clinicians rely increasingly on laboratory tests for the management of patients; for some the stage has been reached when deviation from an accepted range of laboratory values is in itself sufficient reason to justify treatment. The principle is not intrinsically unreasonable but clinical management based solely, or even largely, on such tests implies a confidence in the 'normality' of any given range of laboratory values that is seldom justified.During pregnancy progressive maternal physiological adaptations occur and many biochemical measurements deviate conspicuously from the normal range for males and nonpregnant females. Laboratory ranges specific to pregnancy need to be defined and ideally would be determined in healthy women having uncomplicated pregnancies resulting in the birth of live healthy children; such data are relatively scarce.This paper describes the changes in serum uric acid concentrations throughout normal pregnancy and reports two clinically important aspects. First the values decrease significantly below non-pregnant levels by 8 weeks gestation; second serum uric acid concentrations are not only increased above non-pregnant values by term in many women but remain elevated for as long as 12 weeks after delivery. Such postpartum values should not therefore be used as representative of non-pregnant concentrations. Patients and methods PatientsThirty-one healthy women have been studied; the mean age was 28 (range 23-37) years and each was without any adverse medical, surgical or obstetric history. In five of the women uric acid determinations were repeated during a subsequent pregnancy so that data were obtained from a total of 36 pregnancies. Nine women were primigravidae and 27 were multiparae of whom five had had a previous spontaneous abortion and 22 a successful pregnancy. During the time of this study none of the patients developed medical or obstetric complications or required pharmacological agents including salicylates; all gave birth to live, healthy infants. 128

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