Comparative localization of endothelial and inducible nitric oxide synthase isoforms in haemochorial and epitheliochorial placentae.

The presence and immunolocalization of type II (inducible or macrophage) and type III (endothelial) nitric oxide synthase (NOS) isoforms were compared in the term placentae of humans, rhesus monkeys, baboons, guinea-pigs, rats and sheep using isoform specific antibodies. In the human placenta, intense immunohistochemical staining for type III NOS was seen in syncytiotrophoblast with weaker staining in vascular endothelial cells. Only vascular endothelial cells showed positive III NOS staining in rhesus monkey, baboon, guinea-pig, rat and sheep placentae. No positive type III NOS immunostaining was seen in trophoblast from any non-human placentae. Western blotting revealed a 135-kDa type III NOS species in placental homogenates, semi-purified by ADP-sepharose affinity chromatography, from all the species tested confirming antibody specificity. Type II NOS immunostaining was localized to certain villous stromal cells which also stained for CD14 (a monocyte/macrophage marker) in the placenta of humans, rhesus monkeys, baboons and sheep. No specific immunohistochemical staining for type II NOS or CD14 was noted in the two rodent species, guinea-pig and rat. On Western blots, a 130-kDa type II NOS species was identified in semi-purified placental homogenates of every species except guinea-pig, although weak bands were seen for rhesus monkey and baboon. The failure of the antibodies to show type II NOS in the rat placenta by immunohistochemistry may be due to a difference in antigen conformation from Western blots. As only human placental syncytiotrophoblast expresses type III NOS, the putative functions ascribed to this isoform in syncytiotrophoblast, i.e., to prevent platelet and leucocyte aggregation in the intervillous space and adhesion to the trophoblast surface or to mediate peptide hormone release from trophoblast, may be unique to humans. Alternatively, syncytiotrophoblast-derived NO may fulfill some other unknown function. The similar pattern of expression of type II NOS in those species with villous fetomaternal interdigitation and multivillous fetomaternal blood flow interrelations may represent a more universal role in surveillance and/or protection against maternal insults or pathogens by immunologic activation and subsequent synthesis of nitric oxide which exerts a cytostatic/cytotoxic response.

Associations between placental cadmium and zinc and age and parity in pregnant women who smoke.

We have previously shown that the ratio of placental zinc to placental cadmium (Zn/Cd ratio) is positively related to infant birth weight in pregnant smokers. Clinical studies have reported that older pregnant smokers are at higher risk for impaired fetal growth than younger pregnant smokers. This study examines the relationships among placental cadmium, placental zinc, placental Zn/Cd ratio, age, and parity in 98 smokers and 151 nonsmokers. Atomic absorption spectroscopy was used to analyze cadmium and zinc. Thiocyanate was used as an index of smoking status. The data were analyzed using univariate correlation and repeated-measures analysis of variance. The results showed that increased parity is related to increased levels of placental cadmium in smokers, and decreased placental zinc in smokers and nonsmokers. Age is inversely related to the Zn/Cd ratio in both smokers and nonsmokers; moreover, the oldest nonsmokers have a higher ratio than the youngest smokers. These results are consistent with a depletion of body zinc stores with increasing parity and the long half-life of cadmium in the body. The data explain in part the clinical finding that smoking during pregnancy is more harmful in older women.