/‘lam/a (1991), 12, 79-81
Conference Report: International Conference on Placenta-Tokyo, l-3 October 1990
JOSEPH DANCIS New York University, School of Medicine, !W, US,4
The International Conference on Placenta, representing the combined meetings ofthe Japan Placenta Group, the European Placenta Group and the Rochester Trophoblast Conference, was held in Tokyo, l-3 October 1990. There were 180 registrants, 40 ofwhom had travelled long distances to attend. For many, the meeting provided a cultural as well as a scientific experience. The Tokyo Medical College Hospital, where the conference took place, is a modern facility in the Shinjuku district. The centre of Shinjuku is dominated by newly constructed tall buildings of imaginative architecture, broad streets and plazas, testifying to the economic vigour ofJapan. Presentations by talented young and senior Japanese investigators demonstrated a burgeoning scientific interest in the placenta. A distinctive feature of the conference was the large number of international authorities who were invited to speak on the area of their expertise. The presentations were of high calibre and the subjects were varied and often broad, providing a rich educational experience for the attendees. Adequate summarization of this rich fare is impossible for this reviewer who was further limited by the number of presentations he could attend during concurrent sessions. I will attempt to provide some indication of the tenor of the meeting and the direction that placental research is now taking. Moll described the remarkable adaptive changes in the uterine arteries supplying the placenta of the guinea pig permitting an increase in blood flow at low resistance to maintain nutrient supply to the growing fetus. The peripheral arteries are extensively re-modelled becoming maximally dilated. The factors controlling these changes are unknown, oestradiol remaining a popular candidate, but haemodynamics and other humoral factors must be considered. In the human, a high flow, low pressure maternal circulation to the placenta is also established, in this instance by discharging blood into the intervillous space (Leiser). Intrauterine growth retardation (Carter) can be induced in experimental animals by reducing maternal and fetal blood flows, leading to a reduction in oxygen supply. Acute reductions may be compensated for by increasing oxygen extraction and by metabolic adaptation. More prolonged stress interferes with growth possibly through reduced synthesis of growth factors. Sheppard pointed out that in IUGR and hypertensive pregnancy there is increased fibrin deposition in vessels which could reduce blood flow. A complex haemostatic system with activators and inhibitors synthesized in trophoblast and endothelium, maintains normal blood flow. An imbalance in the fibrinolysis system could cause the described pathology. Using immunohistochemical methods, Faulk extended this theme suggesting that maternal-trophoblast immune reactions could affect the thrombomodulin, coagulantanticoagulant pathways. 0143-4004/91/010079
+ 03 !$0.5.00/0
0
1991 Baillike Tindall I.td
80
Placenra (1991), Vol. I2
Advances in ultrasound techniques (Maulick) have brought closer the hope for accurately identitling the compromised fetus. There is, however, no single test that is clinically reliable. Bohn summarized his extensive experience with placentally synthesized proteins. More than 50 have been identified, many have been purified. Some are proving useful diagnostically, but the biological function of most remains to be elucidated. Grudzinskas has been seeking clinical correlations with pregnancy-associated protein concentrations in maternal blood, urine and amniotic fluid. There are the well known correlations that are already useful in diagnosing pregnancy, early pregnancy failure, spina bifida and trisomy 2 1, and others may be forthcoming. Bischof examined the structural similarities between PAPP-A and complement factor 3 (C,), concluding that Cs is either bound to PAPP-A or that the latter has a subunit homologous to C3. He suggested that PAPP-A, C3, alpha-2 macroglobulin and pregnancy zone protein (PZP) may derive from a single ancestral gene. Boime undertook structure-function studies of hCG, using the technique of mutagenesis followed by transfection of CHO cells. He determined that the carboxyl-terminal amino acids and O-linked oligosaccharides are not essential to receptor binding and signal transduction, but are critical for the biological activity of hCG beta. Beck described a computer-assisted programme to record data on the morphometry ofvilli and presented results of 42 normal placentae which could be used as baselines for the study of pathology. Some of the newer techniques that may be used to relate ultrastructure to function were reviewed by Panigel and the great potential for future study of colloidal gold particles coated with specific proteins was emphasized. Dancis reviewed the development of information and concepts in placental transport made possible by the introduction of new investigative techniques. Boyd traced the effect of gestational age in the rat on transcellular and paracellular placental transport and presented more detailed data on potassium, calcium and magnesium. Miller emphasized that toxic exposure during pregnancy may harm the fetus by affecting placental function; cadmium is concentrated in the placenta of mothers who smoke and perfusion of human placenta with cadmium has been shown to cause structural and functional changes in 4-6 h. In the mouse, oestrogens and progesterone stimulated the synthesis of colony stimulating factor I which recruits large numbers of marcophages to the implantation site where they persist during pregnancy. The macrophages release a variety of cytokines which may have a proliferative and developmental function (Wood). Strauss illustrated the great potential of studying development of trophoblast in tissue culture. He presented a fascinating time-lapse film demonstrating cell fusion and identified some of the factors involved in the process. Young presented the results of experience with 100 chorionic villus biopsies at one institution for prenatal genetic diagnosis. The procedure is accurate and acceptably safe. Two special lectures were given by outstanding Japanese scientists: Y. Oomura on sexual behaviour in monkeys and T. Tada on the immunoregulatory circuit. The scientific programme was completed by 60 contributed papers given in two concurrent sessions and complemented by 19 posters. A broad range of subjects was discussed which cannot be adequately reviewed in the limited space allocated here. In the following, however, the direction and emphasis that current placental research is taking will be described. There were several papers on pathological findings in the placenta in disease, particularly diabetes, hypertension and IUGR. As compared to previous years, there was relatively little investigation of placental transport. In vitro perfusion was used to study the biosynthesis and
7. 1htIci.s: (,‘o?~/iwtlcl~ Kepori
x1
secretion of placental proteins and the transfer of thyroxin and norepinephrin. hlembranc vesicles, apical and basal, were employed for the study of L-tyrosine, amino acids and lactate. Tissue culture of trophoblast and choriocarcinoma was used aggressively to study a Larieh of problems. Growth factors received considerable attention, focussing on identification if their receptor sites and the effects of the factors on trophoblast function. The cytokines nerc grouped with growth factors, both affecting proliferation and differentiation. An obvious source of the cytokines are the macrophages which are found in abundance in endometrium and placenta; however, other potential sources, such as endothelium, must be considered. The effects of retinoic acid, dynorphin (the presumed endogenous opiate) and st.lect xenobiotics on placental metabolism were reported. The attendees expressed their gratitude to Professor H. Soma, to the Japanese organizing committee and the several sponsoring organizations for the stimulating scientific meeting and the warm hospitality extended to all of us.
Conference Report: International Conference on Placenta-Tokyo, l-3 October 1990
JOSEPH DANCIS New York University, School of Medicine, !W, US,4
The International Conference on Placenta, representing the combined meetings ofthe Japan Placenta Group, the European Placenta Group and the Rochester Trophoblast Conference, was held in Tokyo, l-3 October 1990. There were 180 registrants, 40 ofwhom had travelled long distances to attend. For many, the meeting provided a cultural as well as a scientific experience. The Tokyo Medical College Hospital, where the conference took place, is a modern facility in the Shinjuku district. The centre of Shinjuku is dominated by newly constructed tall buildings of imaginative architecture, broad streets and plazas, testifying to the economic vigour ofJapan. Presentations by talented young and senior Japanese investigators demonstrated a burgeoning scientific interest in the placenta. A distinctive feature of the conference was the large number of international authorities who were invited to speak on the area of their expertise. The presentations were of high calibre and the subjects were varied and often broad, providing a rich educational experience for the attendees. Adequate summarization of this rich fare is impossible for this reviewer who was further limited by the number of presentations he could attend during concurrent sessions. I will attempt to provide some indication of the tenor of the meeting and the direction that placental research is now taking. Moll described the remarkable adaptive changes in the uterine arteries supplying the placenta of the guinea pig permitting an increase in blood flow at low resistance to maintain nutrient supply to the growing fetus. The peripheral arteries are extensively re-modelled becoming maximally dilated. The factors controlling these changes are unknown, oestradiol remaining a popular candidate, but haemodynamics and other humoral factors must be considered. In the human, a high flow, low pressure maternal circulation to the placenta is also established, in this instance by discharging blood into the intervillous space (Leiser). Intrauterine growth retardation (Carter) can be induced in experimental animals by reducing maternal and fetal blood flows, leading to a reduction in oxygen supply. Acute reductions may be compensated for by increasing oxygen extraction and by metabolic adaptation. More prolonged stress interferes with growth possibly through reduced synthesis of growth factors. Sheppard pointed out that in IUGR and hypertensive pregnancy there is increased fibrin deposition in vessels which could reduce blood flow. A complex haemostatic system with activators and inhibitors synthesized in trophoblast and endothelium, maintains normal blood flow. An imbalance in the fibrinolysis system could cause the described pathology. Using immunohistochemical methods, Faulk extended this theme suggesting that maternal-trophoblast immune reactions could affect the thrombomodulin, coagulantanticoagulant pathways. 0143-4004/91/010079
+ 03 !$0.5.00/0
0
1991 Baillike Tindall I.td
80
Placenra (1991), Vol. I2
Advances in ultrasound techniques (Maulick) have brought closer the hope for accurately identitling the compromised fetus. There is, however, no single test that is clinically reliable. Bohn summarized his extensive experience with placentally synthesized proteins. More than 50 have been identified, many have been purified. Some are proving useful diagnostically, but the biological function of most remains to be elucidated. Grudzinskas has been seeking clinical correlations with pregnancy-associated protein concentrations in maternal blood, urine and amniotic fluid. There are the well known correlations that are already useful in diagnosing pregnancy, early pregnancy failure, spina bifida and trisomy 2 1, and others may be forthcoming. Bischof examined the structural similarities between PAPP-A and complement factor 3 (C,), concluding that Cs is either bound to PAPP-A or that the latter has a subunit homologous to C3. He suggested that PAPP-A, C3, alpha-2 macroglobulin and pregnancy zone protein (PZP) may derive from a single ancestral gene. Boime undertook structure-function studies of hCG, using the technique of mutagenesis followed by transfection of CHO cells. He determined that the carboxyl-terminal amino acids and O-linked oligosaccharides are not essential to receptor binding and signal transduction, but are critical for the biological activity of hCG beta. Beck described a computer-assisted programme to record data on the morphometry ofvilli and presented results of 42 normal placentae which could be used as baselines for the study of pathology. Some of the newer techniques that may be used to relate ultrastructure to function were reviewed by Panigel and the great potential for future study of colloidal gold particles coated with specific proteins was emphasized. Dancis reviewed the development of information and concepts in placental transport made possible by the introduction of new investigative techniques. Boyd traced the effect of gestational age in the rat on transcellular and paracellular placental transport and presented more detailed data on potassium, calcium and magnesium. Miller emphasized that toxic exposure during pregnancy may harm the fetus by affecting placental function; cadmium is concentrated in the placenta of mothers who smoke and perfusion of human placenta with cadmium has been shown to cause structural and functional changes in 4-6 h. In the mouse, oestrogens and progesterone stimulated the synthesis of colony stimulating factor I which recruits large numbers of marcophages to the implantation site where they persist during pregnancy. The macrophages release a variety of cytokines which may have a proliferative and developmental function (Wood). Strauss illustrated the great potential of studying development of trophoblast in tissue culture. He presented a fascinating time-lapse film demonstrating cell fusion and identified some of the factors involved in the process. Young presented the results of experience with 100 chorionic villus biopsies at one institution for prenatal genetic diagnosis. The procedure is accurate and acceptably safe. Two special lectures were given by outstanding Japanese scientists: Y. Oomura on sexual behaviour in monkeys and T. Tada on the immunoregulatory circuit. The scientific programme was completed by 60 contributed papers given in two concurrent sessions and complemented by 19 posters. A broad range of subjects was discussed which cannot be adequately reviewed in the limited space allocated here. In the following, however, the direction and emphasis that current placental research is taking will be described. There were several papers on pathological findings in the placenta in disease, particularly diabetes, hypertension and IUGR. As compared to previous years, there was relatively little investigation of placental transport. In vitro perfusion was used to study the biosynthesis and
7. 1htIci.s: (,‘o?~/iwtlcl~ Kepori
x1
secretion of placental proteins and the transfer of thyroxin and norepinephrin. hlembranc vesicles, apical and basal, were employed for the study of L-tyrosine, amino acids and lactate. Tissue culture of trophoblast and choriocarcinoma was used aggressively to study a Larieh of problems. Growth factors received considerable attention, focussing on identification if their receptor sites and the effects of the factors on trophoblast function. The cytokines nerc grouped with growth factors, both affecting proliferation and differentiation. An obvious source of the cytokines are the macrophages which are found in abundance in endometrium and placenta; however, other potential sources, such as endothelium, must be considered. The effects of retinoic acid, dynorphin (the presumed endogenous opiate) and st.lect xenobiotics on placental metabolism were reported. The attendees expressed their gratitude to Professor H. Soma, to the Japanese organizing committee and the several sponsoring organizations for the stimulating scientific meeting and the warm hospitality extended to all of us.
