Georg Kosanke

Increased fetoplacental angiogenesis during first trimester in anaemic women

BACKGROUND Epidemiological studies describe an association between relative size of the placenta at delivery and cardiovascular morbidity and mortality during adult life. Some determinants of placental size, such as maternal anaemia, have been acknowledged, but no plausible mechanism has been advanced to explain the initiation of postnatal disease. METHODS Placental villous vascularisation in anaemic women (Hb<90 g/L) was assessed in the first and third trimesters of pregnancy by immunohistochemical identification of villous capillaries and compared with that of gestational age-matched groups of women with normal (Hb>110 g/L; control group) concentrations of haemoglobin, and an intermediate group (Hb 90-110 g/L). FINDINGS Anaemia, especially in the first trimester, was associated with increased numbers of capillaries per villous cross section (mean 11.70 [SE 0.35] vs 4.14 [0.27]) located mainly in the outer third of the stroma beneath the trophoblast (94% [1.15] vs 67% [1.82]) and with increased numbers of villous macrophages and of proliferating MIB-1-positive cells compared with the control group. INTERPRETATION Maternal anaemia in early pregnancy seems to influence the pattern of placental vascularisation. Such changes might alter placental vascular impedance during early fetal life, thereby exerting important effects on cardiovascular development.

CLASSIFICATION OF HUMAN PLACENTAL STEM VILLI : REVIEW OF STRUCTURAL AND FUNCTIONAL ASPECTS

The stem villi of the human placenta represent the central branches of the villous trees. They are characterized by a condensed fibrous stroma in which the fetal arteries and veins as well as the arterioles and venules are embedded. Functionally they are accepted as the mechanically supporting structures of the villous trees, and they are supposed to control fetal blood flow to the maternofetal exchange area, which is located in the peripheral villi. To obtain further insights into the functions of the stem villi, the recent literature has been reviewed, and some immunohistochemical, ultrastructural, and reconstruction studies have been added. These new studies were aimed at identifying immunohistochemically different subtypes of stem villi, their branching patterns, the distribution of macrophages, the stromal proliferation patterns, and the differentiation of extravascular stromal cells. Our findings demonstrate that the stem villi and their precursors, the immature intermediate villi, can selectively be identified by anti‐γ‐smooth muscle (sm) actin staining. Furthermore, the existence of three different subtypes of stem villi is shown; these differ regarding the presence and distribution of γ‐sm actin‐positive cells. These cells were immunohistochemically and ultrastructurally identified as smooth muscle cells and myofibroblasts. Increasingly complex coexpression patterns of cytoskeletal proteins reflect a clearly defined differentiation gradient of extravascular stromal cells, which covers the whole range of an undifferentiated germinative layer beneath the trophoblast to highly differentiated myofibroblasts surrounding the medias of the stem vessels. Possible functions of the extravascular contractile system include the regulation of villous turgor and the control of intervillous blood flow impedance. Microsc. Res. Tech. 38:29–41, 1997.

Maternal anemia results in increased proliferation in human placental villi

Summary Maternal anemia results in hypoxic conditions of the feto-placental unit and thus is a suitable model to study the effects of hypoxia on villous proliferation in human placentae. Preliminary experiments revealed considerable discrepancies between the results gained with several proliferation markers and between our findings and the literature. Thus, in a pilot series we performed double labeling experiments with 3H-TdR autoradiography combined with the immunohistochemical proliferation markers MIB 1 and PCNA (clones PC 10, 19A2, and 19F4). This pilot series revealed MIB 1 to be the most reliable immunohistochemical proliferation marker for paraffin-embedded human placental tissues. In a second series, we investigated 12 placentae from first trimester (8 to 10 weeks gestation) and 12 placentae from third trimester (34 to 40 weeks of gestation) using MIB 1 as immunohistochemical proliferation marker. Maternal anemia was divided into two groups, severe (Hb

Pressure dependence of so‐called transtrophoblastic channels during fetal perfusion of human placental villi

To test the influence of perfusion pressures on structural preservation of human placental villi and on the dilatation of the so‐called transtrophoblastic channels, cotyledons of 32 term human placentas have been perfused in vitro. Periods of perfusion with isotonic Ringer solution under various arterial and venous hydrostatic pressures were followed by perfusion fixation. In some experiments, lanthanum hydroxide as an extracellular marker was added to the fixative. Distention of the fetal vascular system, stromal edema and continuity, as well as trophoblastic vacuolization were studied via electron microscopy with subsequent morphometry. The findings suggest that arterial hydrostatic pressures in the perfusion system of about 80 cm H2O are needed to guarantee homogeneous perfusion of the fetal vascular system. To avoid stromal edema and trophoblastic vacuolization, venous hydrostatic pressures of 4 cm H2O and arterial hydrostatic pressures of 80 cm H2O should not be exceeded. It is concluded that the trophoblastic vacuoles are dilated segments of the so‐called transtrophoblastic channels. The functional importance of in vivo variations of fetal intravascular hydrostatic pressure for the dilatation of transtrophoblastic channels and for fetal water balance is discussed. Microsc. Res. Tech. 38:52–62, 1997.

Branching patterns of human placental villous trees: Perspectives of topological analysis

Topological analysis was applied to investigate the branching pattern of three specimens obtained from early human placenta (6, 9, and 16 weeks p.m.) reconstructed on the basis of semi-thin sections. Centripetal Horton-Strahler and centrifugal branching order nomenclature was used for topological description of the analysed tree-like structures. Bifurcation ratio and vertex ratio were determined for all three cases and were found to be relatively constant. It was shown that branching pattern is closely related to the model of random segment branching that implicates a high level of asymmetry and a small level of space limitation for branching. The significance of this approach for the analysis of development of the villous tree, for the analysis of mesenchymal villous heterogeneity, and for the estimation of physiological parameters for fetoplacental exchange is discussed. We suggest that topological analysis can lead to a new quantitative classification of branching patterns of the human placental villous trees in normal and pathologic pregnancies.

Is there morphological evidence for the existence of transtrophoblastic channels in human placental villi

Summary Earlier transfer experiments have given evidence for the existence of water-filled, membrane-lined routes across the trophoblast of the rabbit and the guinea pig placentae; structurally, they seemed to correspond to transtrophoblastic channels which were thought to pass through the guinea pig syncytiotrophoblast from the apical to the basal surface. To test whether such channels are present or not also in the human placenta, the pre-rinsed, unfixed or perfusion-fixed feto-placental circulation of term human placental cotyledons was perfused with various lanthanum hydroxide preparations as extracellular tracer, using arterial pressures of 50 to 60 mm Hg and venous pressures below 5 mm Hg. The results were evaluated electron microscopically and morphometrically. We demonstrate a lanthanum filled, branching, and winding system of about 20 nm wide channels originating from the basal plasmalemma infolding and extending near to the apical syncytiotrophoblastic surface. Traces of lanthanum hydroxide appearing after longer lasting experiments along the maternal trophoblastic surfaces, suggest that the channels completely pass through the syncytiotrophoblast. Even though unlikely, it cannot completely be ruled out that under normal pressure conditions an apical gap of about 0.5 μm length is bridged by a vesicular shuttle. Quantitative estimations point to a highly convergent transtrophoblastic channel system: we found about 15 channel openings per μm2 of basal syncytiotrophoblastic surface, as opposed to only 0.025 to 3.2 channel openings calculated by physiologists for each μm2 of apical surface. Structural and experimental evidence is provided that the channel are routes for the recirculation of plasma membrane from the basal to the apical plasmalemma. The data fit into physiological concepts requiring 20 nm routes which allow unrestricted transtrophoblastic diffusion of water-soluble molecules with an effective molecular radius up to 2.0 nm. Pressuredependent dilation and closure of these channels, controlling feto-maternal fluid shift, may regulate fetal osmotic pressure and water balance.