D.R. Abramovich

Circulating leptin in women: a longitudinal study in the menstrual cycle and during pregnancy

To investigate whether leptin is linked to reproduction, circulating levels were measured longitudinally throughout spontaneous menstrual cycles and during pregnancy in normal women.

Long-chain polyunsaturated fatty acid transport across the perfused human placenta

The role of the placenta in controlling the supply of fatty acids to the fetus was investigated in term placentae (n = 9) from normal pregnancies. The maternal side was perfused ex vivo for 90 min with a modified Krebs Ringer solution containing a physiological mixture of fatty acids and ratio of fatty acid to human albumin. There was no evidence of chain elongation and desaturation of the essential fatty acids. Relative to the value for oleic acid, the rate of transfer to the fetal circulation was: 1.30 +/- 0.02 (P < 0.001) for linoleic acid, 1.61 +/- 0.09 (P = 0.002) for alpha-linolenic acid, 0.67 +/- 0.10 (P = 0.033) for arachidonic acid and 2.10 +/- 0.16 (P = 0.003) for docosahexaenoic acid. For tissue accumulation the values were 1.47 +/- 0.39 (P < 0.001) for linoleic acid, 2.24 +/- 0.37 (P = 0.027) for alpha-linolenic acid, 9.84 +/- 1.03 (P = 0.001) for arachidonic acid, and 3.01 +/- 0.79 (P = 0.064) for docosahexaenoic acid. The order of selectivity for transfer from the maternal to the fetal circulation was docosahexaenoic > alpha-linolenic > linoleic > oleic > arachidonic acid. Such a mechanism would allow the preferential transfer of docosahexaenoic acid and the essential fatty acids to the fetal circulation, thereby protecting the polyunsaturated fatty acid supply to the fetus during a critical period of development.

Stage-specific distribution of P-glycoprotein in first-trimester and full-term human placenta.

SummaryThe distribution of P-glycoprotein in human placenta has been examined by immunohistochemistry using a battery of monoclonal antibodies (MRK-16, C219 and JSB-1). P-glycoprotein was located on the syncytiotrophoblast microvillus border in first-trimester placentas and some of the placental macrophages (Hofbauer cells) showed weak cytoplasmic staining. In term placentas, however, staining was not observed in the trophoblast but most of the Hofbauer cells displayed strong cytoplasmic staining. In situ hybridization with specific gene probes suggested that both human multidrug resistance genes were expressed in the placenta, although only the multidrug resistance-1 gene product would have been detected by the MRK and JSB-1 antibodies. These results point to distinct functions for P-glycoprotein during the different stages of placental development and indicate that its expression may be under developmental control.

Ponderal index is a poor predictor of in utero growth retardation

Objective  To evaluate the usefulness of ponderal index (PI) and related indices of weight and length in identifying asymmetric growth, body thinness and organ asymmetry associated with IUGR.

Uptake of Zinc by Human Placental Microvillus Border Membranes and Characterization of the Effects of Cadmium on this Process

The uptake of Zinc (Zn) by microvillus border membrane vesicles formed from the trophoblast of term human placentae is markedly increased over brief periods of incubation with much slower increases persisting for up to 2 h of incubation. Zinc is both bound to membrane components and transported into intravesicular osmotically active space. Uptake is saturable, temperature dependent from 4 to 37 degrees C with a Q10 of 1.7, and is inhibited by the sulphydryl agent DTNB. About 20 per cent of the uptake is susceptible to inhibition by Cadmium (Cd) at concentrations from 5 to 50 microM, a significant part of the action of this metal being on the transmembrane component of Zn uptake.

Inhibitor action on placental calcium transport

SummaryHuman term placental lobules were dually perfused with Krebs Ringer solution at 37°C under open circuit conditions. Provided that perfusate Ca2+ concentrations were between 2.33 and 2.55 mM, there was a steady release of Ca2+ into the fetal circulation and uptake of Ca2+ from the maternal circulation. There was no significant calcium (Ca) protein binding in the perfusates. Addition of dinitrophenol altered the release of Ca2+ to an uptake on the fetal circuit and enhanced Ca2+ uptake on the maternal circuit. It also produced a release of potassium (K)+ and an uptake of Na+ on both sides of the placenta. Ouabain had no significant effect on Ca movements although it produced a marked release of K+ into the fetal perfusate. The effect of cooling on the fetal circuit was similar to that of dinitrophenol (DNP), although it did not produce significant changes in either Ca2+ or K+ movements on the maternal side of the lobule. Both DNP and cooling reduced the Ca concentration ratio between fetal and maternal outflows to unity. Replacement of Na+ by choline Ringer had only transient effect on the extraction of45Ca from fetal perfusate. These observations indicate that a Ca2+/Na (sodium)+ exchanger does not make a major contribution to the transplacental movement of Ca2+ from mother to fetus and that this process is more probably associated with membrane-bound ATPases.

Changes in foetal liver T2* measurements by MRI in response to maternal oxygen breathing: application to diagnosing foetal growth restriction

The motivation of the project was to investigate the use of oxygen-challenge magnetic resonance imaging (OC-MRI) as a method of diagnosing foetal growth restriction. Foetal growth restriction is associated with restricted foetal oxygen supply and is also associated with increased risks of perinatal mortality and morbidity, and a number of serious and chronic health problems. Measurements of T2* relaxation time, an MRI parameter which increases with blood oxygenation, were made in the right lobe of the foetal liver in 80 singleton pregnancies, before and after the mother breathed oxygen. The groups consisted of 41 foetuses with normal growth and 39 with apparent growth restriction. The mean +/- SD gestational age at scanning was 35 +/- 3 weeks. Changes in foetal liver T2* on maternal oxygen breathing showed no significant difference between the groups therefore the OC-MRI protocol used in this study has no value in the diagnosis of foetal growth restriction. A secondary finding was that a significant positive correlation of T2* change with gestational age was observed. Future studies on the use of oxygen-challenge MRI to investigate foetal growth restriction may therefore need to control for gestational age at the time of MR scanning in order to observe any underlying foetal growth-related effects.

The effects of smoking on placental membranes

Ingested tobacco smoke contains many toxic components that may harm the membrane compartments of the human placenta. The effects of maternal smoking on placental membrane structure are examined by stereological methods and related to smoking habit. A significant decrease in fetal capillary volume and increase in the diffusion distance across the trophoblastic epithelium is observed. The stereologically-determined structural variables are used to estimate both total and partial oxygen diffusive conductances. The total diffusive conductance is found not to alter with smoking; however, changes in partial conductances and the haematocrits of both maternal and fetal blood, indicate hypoxic stress is associated with smoking. However, a component of the placental membranes responsible for the transport of alanine is shown to be altered. An increase in the sodium-dependent transport of alanine across the microvillous border membrane of the placenta is observed in tissues derived from mothers who smoke. This may be an adaptive response to a deficient supply of this amino acid to the placenta.

Protein Release by the In Vitro Human Placental Lobule when Dually Perfused by Different Protocols

Alone of the in vitro methods of studying placental function, the dually-perfused placenta preserves the integrity of the fetal and maternal circulations so allowing studies of the “sidedness” of the organ, a point of particular relevance to feto-maternal endocrine physiology. Difficulties in studying the whole human placenta arise from the problems of obtaining a complete, uninjured specimen, and in maintaining adequate perfusion of the entire intervillous space. These difficulties may be minimised by perfusing a limited region of the placenta only, typically a lobule of 25 g wet weight.1 Lobules selected for this purpose are each supplied by a single fetal artery and vein which may be cannulated from the fetal surface. The maternal aspect is perfused by glass cannulae inserted into the lobular intervillous space, the outflow being collected by drainage from the maternal plate. The perfusate is a physiologically balanced solution such as Earle’s culture medium, Medium 199, or Krebs Ringer containing either albumin or Dextran. Perfusions can be maintained for three to 12 hours.

Erratum to “The effects of smoking on placental membranes” ☆: [Journal of Membrane Science 206 (2002) 243–252]

K.R. Page a,∗, P. Bush b, D.R. Abramovich c, P.J. Aggett d, M.D. Burke e, T.M. Mayhew f a Department of Biomedical Sciences, University of Aberdeen, Aberdeen, Scotland, UK b Department of Biomedical Sciences (Physiology), University of Edinburgh, Edinburgh, Scotland, UK c Department of Obstetrics and Gynaecology, Aberdeen University, Aberdeen, UK d Lancashire Postgraduate School of Medicine and Health, University of Central Lancashire, Preston, UK e School of Pharmacy and Pharmaceutical Sciences, De Montfort University, Leicester, UK f School of Biomedical Sciences, Queens Medical Centre, Nottingham University, Nottingham, UK