This study demonstrates that IgG transfer in vitro across the isolated perfused human placental lobule can be successfully studied by using natural forms of IgG. The transfer of anti-RhD IgG (anti-D) was measured in the presence and absence of intravenous immunoglobulin (IVIgG). When anti-D and IVIgG were present alone each crossed the placenta at about the same rate, but when both forms were present at the same time the movement of one interfered with the movement of the other. This pattern of transfer is consistent with receptor-mediated transcytosis. The interactions of IgG with trophoblastic transporters may therefore be studied without the complications that might arise from the use of conventionally labelled molecules.
SUMMARYDually perfused human term placental lobules were exposed to forskolin, bovine parathyroid hormone (bPTH(1-34)) and human parathyroid hormone related-peptides, hPTHrP(1-34), hPTHrP(67-86)NH2 or PTHrP(107-138) for 15 min in the presence of 3-iso-butyl-1-methylxanthine (IBMX); control lobules were exposed to IBMX alone. Homogenates of these tissues were then assayed for cyclic adenosine 3',5'-monophosphate (cyclic AMP) and results normalized per mg of protein. Exposure to forskolin or bPTH(1-34) on both sides, and exposure to bPTH(1-34) at a concentration of 30 nm on the maternal side of the placenta or 120 nm on the fetal side of the placenta, significantly enhanced tissue cyclic AMP production compared with tissue exposed to IBMX alone. Exposure to hPTHrP(1-34), hPTHrP(67-86)NH2 and hPTHrP(107-138) at a concentration of 30 nm on both sides of the placenta had no significant effect upon tissue cyclic AMP production.
There have been a number of reviews on this topic over the past decade, starting with Carlsen et al. and including Irvine et al. and Murray et al., concerning declining male fertility. The most exhaustive has perhaps been that of Toppari et al. The main findings of these reviews are: (1) that in some countries of the world sperm production has halved in the last 60 years, (2) rates of testicular cancer have doubled, (3) rates of malformation of the male reproductive tract, such as hypospadias, have doubled, (4) rates of testicular maldescent have risen sharply and (5) these effects are largely linked geographically. Typically, endocrine disrupting chemicals (EDCs) in the environment have been regarded as the main candidates for these effects. A consistent problem with the field, however, is the difficulty in determining the accuracy of data relating to changes in men's health over the latter half of the 20th century. Advances in diagnosis and changing attitudes to the emotive issues surrounding deformity and male infertility inevitably render some of the mass of collected data suspect. Indeed a recent review of testicular and prostate cancer concluded that while the incidence of prostate cancer had increased, the epidemiological data were not suitable for concrete conclusions about causation to be drawn. However, in the case of testicular cancer the data suggested a limited number of major risk factors. In addition, assessing urogenital malformation retrospectively from patient notes is subject to considerable variation in classification. A recent review does however find evidence to suggest that trends of increasing incidences of hypospadias on a temporal and geographical basis may reflect an actual increase in incidence and require further study. On the other hand, there is a considerable body of evidence for EDC disruption of reproduction in wildlife (reviewed by Guillette & Gunderson, 2001).
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