[Angiogenesis-related factors in the placenta of pregnant women with congenital heart diseases]. / Faktory angiogeneza v platsente beremennykh s vrozhdennymi porokami serdtsa.

OBJECTIVE: To study the features of angiogenesis of the placental villous chorion in women whose gestation took place in congenital heart disease (CHD). MATERIAL AND METHODS: Thirty-five placentas obtained from women with full-term pregnancy, including 20 cases of non-operated CHD and 15 as a result of physiological pregnancy and childbirth (a control group), were studied. A placental morphological examination was made according to the standard scheme using routine stains and immunohistochemical techniques involving reactions with mouse monoclonal antibodies against VEGF, CD34, and SMA. RESULTS: The placentas of women with CHD showed a set of pathological changes, including impaired chorionic villous maturation and marked dystrophic and necrobiotic changes, the latter being more common in the placental marginal zones. Placental VEGF expression in women with CHD was significantly higher than that in the controls, especially at the edge of the placental disc. On the contrary, CD34 expression in all placental sections was lower in CHD. The distribution of SMA in the myofibroblasts of chorionic villous vessels in CHD was characterized by diffuse growth of actin expression. The specific volume of the cell surface with a positive reaction to actin significantly increased in the center, especially in the peripheral zone. CONCLUSION: Thus, the analysis of the studies could establish that hemodynamic disturbance during gestation complicated by CHD was accompanied by remodeling of the villous chorion. Pathological changes in the placental barrier complicate metabolism and gas exchange in the fetoplacental complex. Microvascular remodeling is an important mechanism of placental adaptation to circulatory hypoxic conditions in the presence of CHD and a prerequisite for successful pregnancy termination and childbirth in disease.

[Antenatal factors of caries susceptibility formation in children].

The role of the intrauterine growth retardation (IUGR) in the remodeling of a fetal parotid gland at late pregnancy has been presented in the paper. Thirty fetal parotid glands at 20-22 weeks gestation, including, 20--with IUGR and 10--at physiological pregnancy (control) were studied morphologically and morphometrically. Results have shown violations of gland's growth and differentiation, increased volume fraction of pathologic changes. Above mentioned processes may cause salivary glands' dysfunction, which eventually could result in child's dental caries.

[Human placenta barrier remodelling under different type of hypoxia]. / Remodelirovanie platsentarnogo bar'era cheloveka pri gipoksiiakh raznogo geneza.

The stereological investigation was performed on intermediate and terminal villi of placenta obtained from each of the following conditions: high altitude (up to 2800 m), maternal anemia and EPH-gestosis. These conditions were taken to represent hypoxic, anemic and ischemic hypoxia, respectively. In each situation there was a trend for both the volume of trophoblast and stroma to be lower than in controls with accompanying increase in the volume fraction of fetal capillaries, although the differences were statistically significant only for cases of hypoxic and anemic hypoxia. The capillary diameter was higher in EPH-gestosis group. There was no evidence of "hypercapillarization" of the villi because the relative capillary length was constant in all the groups. The harmonic mean thickness in anemia and altitude groups was reduced. As a result a specific and morphometric (per 1 kg of fetal weight) diffusing capacity was maintained at the control level, but at the altitude group it was even higher. These results suggest that placenta barrier remodelling is the principal mechanism of adaptation to different forms of hypoxia.

Increased incidence of placental chorioangioma in high-altitude pregnancies: hypobaric hypoxia as a possible etiologic factor.

OBJECTIVES: Our purpose was to determine the effects of pregnancy at high altitude on the human placental structure. STUDY DESIGN: Histologic material from 22 term placentas delivered at altitudes above 3600 m was examined and compared with control material from 760 m. RESULTS: Intraplacental chorioangiomas were identified in 5 of the 22 high-altitude placentas but in none of the 59 controls. The lesions were not visible on the external surface of the placentas and were not encapsulated. The state of differentiation varied; some contained numerous capillaries that showed sinusoidal dilations, whereas in others at the opposite extreme mesenchymal cells predominated. The presence of chorioangiomas was frequently associated with threatened premature delivery, a circumvallate placenta, and multiple infarction. The lesions represented only a small percentage of the overall placental volume (<10%). CONCLUSIONS: The increased incidence of placental chorioangioma observed at high altitude (above 3600 m) may be due to the prevailing hypobaric hypoxia. Overexpression of angiogenic cytokines such as vascular endothelial growth factor, which is known to be up-regulated by this factor in vitro, may mediate this effect.

Stereological evaluation of vascular adaptations in human placental villi to differing forms of hypoxic stress.

The aim was to determine whether the fetal vasculature of the human placenta adapts in a uniform manner to different forms of hypoxic stress. Stereological analyses were performed on the intermediate and terminal villi of placentae obtained from each of the following conditions; high altitude (up to 2800 m), maternal iron-deficiency anaemia and pre-eclampsia. These conditions were taken to represent hypoxic, anaemic and ischaemic hypoxia, respectively. In each situation, there was a trend for the volume fraction of the fetal capillaries to be higher than in the controls, although the differences were statistically significant only for the cases of hypoxic and anaemia hypoxia. This was due, in part, to capillaries being of larger diameter. Evidence for capillary proliferation was inconsistent. At high altitude there was a trend for the capillary length density to be raised, but there was no change in the ratio of capillary:villous length. In both maternal anaemia and pre-eclampsia the capillary length density remained constant, but the ratio of capillary:villous length was significantly raised in the former. These results suggest that dilatation of the capillary sinusoids, with accompanying thinning of the villous membrane, is the principal adaptation to hypoxia under the conditions studied.

Placental histomorphometry and morphometric diffusing capacity of the villous membrane in pregnancies complicated by maternal iron-deficiency anemia.

OBJECTIVE: Our purpose was to determine the morphometric diffusing capacity of the human placental villous membrane in cases of maternal iron-deficiency anemia. STUDY DESIGN: Material from 10 term placentas from mothers with hemoglobin levels < 10 gm/100 cm3 was compared stereologically with control material from women with normal hemoglobin concentrations matched for age and parity. Data were compared with Student t test. RESULTS: Birth and placental weights were constant between the two groups. Maternal anemia was associated with a significant reduction in both volume and surface area of intermediate and terminal villi (157.8 vs 234.5 cm3 and 9.5 vs 14.9 m2, respectively). There was a concomitant rise in the volume of pathologic areas (32.1 vs 4.1 cm3). Harmonic mean thickness of the villous membrane was significantly less in the anemia cases (5.86 vs 7.15 microns), because of an increase in volume fraction of the fetal capillaries. Consequently, the morphometric diffusing capacity of the villous membrane was maintained (4.49 vs 5.31 cm3.min-1.mm Hg-1, t = 1.04, p > 0.05). CONCLUSIONS: There is a reduction rather than an enlargement of the placental villous tree in cases of maternal anemia. This may be because of underlying malnutrition. Nonetheless, the placenta adapts through thinning of the villous membrane so that diffusing capacity is maintained at normal levels.

Effects of hypobaric hypoxia on the fetoplacental unit: the morphometric diffusing capacity of the villous membrane at high altitude.

OBJECTIVE: Our purpose was to determine whether the human placenta is able to adapt structurally to hypobaric hypoxia so as to increase its diffusing capacity. STUDY DESIGN: Material from 10 normal term placentas collected at each of three altitudinal levels in Kirghizstan was analyzed stereologically. Data were compared by one-way analysis of variance. RESULTS: Within the overall sample group birth weight and placental weight remained constant. There were no differences in villous and capillary surface areas or capillary length, but capillary volume increased from 37.9 cm3 in controls (700 m) to 50.8 cm3 at high altitude (2200 to 2800 m). The harmonic mean thickness fell from 6.9 microns in controls to 4.8 microns at high altitude. Consequently, the morphometric diffusing capacity of the villous membrane for oxygen increased from 4.22 to 7.56 cm3.min-1.mm Hg-1 (F = 6.45, p < 0.05). CONCLUSIONS: The placenta is capable of adapting to hypobaric hypoxia to increase its functional capacity for gaseous exchange. This is principally through a reduction in the thickness of the villous membrane.

[Structural adaptation of the placenta in natural hypoxia at moderate and high altitude]. / Strukturnaia adaptatsiia platsenty v usloviiakh prirodnoi gipoksii srednegor'ia i vysokogor'ia.

26 placentas of Kirghiz women from the town of Narin situated at the altitude of 2020 m above the sea level (moderate altitude), 22 placentas of women from Murgab (3600-3800 m above the sea level, high altitude) and 22 placentas of Frunze city (760 m, control) women were studied by means of organo--and stereometry using a standardized schema. A body weight decrease of newborns and placentas was established in the rating: control--moderate--high altitude. "Miniaturization" of foetuses is a response to the natural deficiency of oxygen in the atmospheric air. Moderate hypoxia has a training effect on the placenta while hypoxia associated with high altitude is followed by its dysadaptation. The role of placenta in the mechanisms of the foetus development inhibition under the conditions of natural hypoxia is suggested.

[Morphofunctional adaptation of the placenta under conditions of natural high-altitude hypoxia]. / Morfofunktsional'naia adaptatsiia platsenty v usloviiakh prirodnoi vysokogornoi gipoksii.

Twenty-six III trimester placentae from Kirghiz puerperas residents of high-altitude regions (2200-3000 m above the sea level) and 22 such placentae from female residents of the plains (group I and II, respectively) were subjected to ultrasonic placentometry and organo-stereohistometry. Group I placentae appeared to fall behind in thickness on weeks 28, 32 and 36 as well as in development on the last 4 weeks which is coupled with synchronous reduction of weight of mature newborns and relevant placentae. Enhanced morphofunctional activity, excessive vasculature of villous network, increased epithelial volume of the villi and vascular-syncytial membranes, intensive growth of separate cotyledons were characteristic for placentae exposed to high-altitude factors, which also bore the signs of dysadaptation manifesting with more frequent infarctions, adherent villi, hemorrhages.

[Structural and metabolic mechanisms of placental adaptation]. / K voprosu o strukturno-metabolicheskikh mekhanizmakh adaptatsii platsenty.

Ninety-two placentas from patients with late toxaemia of pregnancy were studied by means of histologic, stereologic and enzyme histochemical methods. 32 placentas were from live births and 60 from stillbirths. In the stillbirth series, 31 placentas were from cases of fetal antepartum deaths and 29 from cases of fetal intrapartum deaths. The increase of the microcirculation volume in placental villi and the increase of oxidative enzyme activity in the syncytiotrophoblast, stroma and villi vesel wall are considered as structural and metabolic mechanisms of placenta adaptation. The role of structural and metabolic placenta insufficiency in the pathogenesis of the intrauterine fetal death is discussed.