Development of the uterine microcirculatory bed in postnatal ontogeny

Age peculiarities of common structure of the microcirculatory pathways, specific volumes and amount of microvessels, zonal parameters of pericapillary microcirculation of metabolites, glycosamine glycans and glycoproteins contents, phosphatase and ATPase activity, collagen and elastic fibers of the microcirculatory bed vessels have been studied in 190 unchanged uteri, beginning from 36-week-old fetuses up to 35 years of age. The microcirculatory bed of myometrium during the period of postnatal ontogenesis investigated possesses a polymer-homonomous structural organization; its base make myoangiomas, including the terminal arteriole with precapillaries and collecting venule, that run from it. Similar structure of the myometrium microcirculatory pathways is already observed in fetuses of late antenatal period. In endometrium formed glanduloangionomas are revealed in the prepubertal age. Increase in glycosamine glycans contents is stated in the microvessel walls and in the uterine stroma during the process of its development. Compensatory-adaptive changes in the uterine microcirculatory bed are described during the newborn period up to the puberty. Functionally mature structures of the microcirculatory pathways in the submucosal and vascular layers of myometrium, endometrium and in the cervix uteri are found to be formed earlier than in other areas of the organ.     

Formation of structuro-functional units of the microcirculatory bed of muscles in the postnatal period of the ontogenesis of the white rat

By means of biomicroscopy, histological methods and scanning electron microscopy topological relationships between the white rat m. cremaster microvessels and changes of their spatial organization have been studied in the postnatal development beginning from the 3d to the 14th week. In the terminal link of the microcirculatory bed zonal functional complexes of microvessels--myoangions are revealed. They represent rather autonomic and regularly repeating constructions of microvessels, having spatial regularity in respect to muscle fibers. With age the myoangion increases its stretchness from 303 +/- 14 in 3-week-old up to (70 +/- 3) X 10 mcm in 14-week-old animals. Capillary density in the m. cremaster during the development decreases from 354 +/- 12 up to 210 +/- 4 mcm, respectively. Distance between the longitudinal capillaries increases from 16.1 +/- 1.3 up to 31.2 +/- 1.8 mcm. Increase of transversal connections takes place in the capillary network, increasing number of the branching knots; this demonstrates certain complication of the nutritive link of the muscle microcirculatory bed. By the time of sexual maturation (6 weeks) there is a sharp decrease of the inflow and outflow coefficients. Higher meanings of the coefficient (0.70-0.74) are noted before sexual maturation period in comparison to that in mature animals (0.53-0.55).     

Development of the microcirculatory bed of the human tongue in the prenatal period

Morphofunctional regularities of formation and development of the blood microcirculatory bed in the human tongue have been studied in the prenatal period of morphogenesis. 119 human embryos and fetuses at the age of 5 weeks--9 months have been investigated. A complex of methods have been used: common histological (hematoxylin--eosin, after van Gieson and Mallory), injection of the lingual vessels with 20% suspension of Indian ink--gelatin, transmissive electron microscopy. General regularities of organogenesis, stages of the blood microcirculatory bed development and peculiarities of the process on formation of the primary protocapillary lingual blood bed are revealed. Regularities in structure of the terminal vascular constructions are studied for each structural element of the organ--mucosal membrane, muscles, glands, lingual tonsil. For these elements at the ultrastructural level certain features of the organic specificity in the structure of the blood microcirculatory bed links are determined.     

Microcirculatory bed of the bulbar conjunctiva in 3- to 9-month-old fetuses

In 32 corpses of 3-9-month-old fetuses the diameter, length amount of the microcirculatory bed vessels and their wall thickness have been studied in different areas of the eye bulb conjunctiva by means of impregnation after Kuprianov. General morphofunctional vascular peculiarities have been revealed. They are connected with age and structure of the developing tissues in the eye bulb conjunctiva. Two stages of development have been defined: 3-6 and 7-9 months.     

Ultrastructure of human adrenal glands at various periods of prenatal morphogenesis

As demonstrates the electron microscopical investigation of the adrenals in human embryos and fetuses 6--32-week-old, at the age of 10--12 weeks glomerular and fasciculo-reticular zones are already differentiating. Subsequently, during following stages of the prenatal morphogenesis, when ultramicroscopical signs of the zonal belonging of cells and specific activity of steroid-synthesizing organells, the cortical reaction to the birth stress is manifested. Installation of the cells of the medullary substance takes place along nervous fibers, via paravasal and intravascular ways. Formation of the medullary substance by the time of birth is evidently not completed. Some critical estimations on the well known concept of the fetal cortex are presented. As the authors think, it needs to be recomprehended.     

Analysis of metopirone-induced hypertrophy of adrenals in fetal rats encephalectomized in utero

Pregnant rats were treated with 30 mg metopirone (M) each day for 2 days and autopsied on the third day in various gestational periods (Days 18-20, 19-21, and 20-22). Control rats were treated with saline alone (S). The adrenals of intact fetuses in M-treated dams were significantly heavier than those of intact fetuses in S-treated dams in every experimental period. In both M- and S-treated dams, the adrenals of encephalectomized (E) fetuses were lighter than those of intact littermates. However, in the experimental period of Days 18-20 and 19-21, the adrenals of E fetuses in M-treated dams were slightly but significantly heavier than those of similar E fetuses in S-treated dams. In contrast, in the experimental period Days 20-22, there was no significant difference in the weight of adrenals of E fetuses of M- and S-treated dams. These changes in fetal adrenal weight were reflected histologically in parallel changes in the size of adrenocortical cells. The observations suggest that the fetal adrenal hypertrophy following maternal treatment with metopirone can occur to some extent independent of the fetal brain, but that close to the end of gestation the hypertrophy occurs completely under the control of the fetal brain.     

Morphological characteristics of nerves of the vascular plexuses in the lateral cerebral ventricles of human fetuses

The vascular plexus of the lateral ventricle of the human brain includes the microcirculatory bed responsible for the blood supply and liquor production of the organ. Blood capillaries form a thick parviansiform network of the plexus. Innervation of the vascular plexus of the cerebral lateral ventricle in human embryos and fetuses develops synchronously with formation of the plexus itself. The structural complexity of the nervous apparatus increases at the expense of increasing number of nervous fasciculi and single nervous fibers. By the time of birth the nervous apparatus of the plexus acquires a definitive character. After birth further improvement of the nervous apparatus takes place. The role of the microcirculatory bed and of the nervous apparatus of the vascular plexus in ensuring functional loadings and their participation in reactions to certain pathological effects is substantiated.     

Morphologic mechanisms of blood flow regulation in the hemomicrocirculatory system of the human heart during ontogenesis

Hearts of 220 human corpses, who had not any cardiovascular system disease during their life, have been distributed into age groups, beginning from fetuses up to old age. By means of injection, silver nitrate impregnation and scanning electron microscopy methods, applied to corrosive preparations, morphological mechanisms of the blood stream regulation in the hemomicrocirculatory bed of the human heart have been revealed in ontogenesis. The first group of the regulation mechanisms includes proper mechanisms inherent in the links of the microbed: spatial orientation of microvessels, precapillary sphincters, anastomoses between these vessels, sequence in arrangement of the endothelial cell nuclei, length, diameter and number of links in the microcirculatory bed. The second group embraces those mechanisms, that depend on structure of the myocardial wall, influencing the microcirculatory bed.     

Patterns in the development of the ultrastructure of elements of the microcirculatory system in the early stages of human embryogenesis

By means of transmissive electron microscopy methods, general regularities in development of the microcirculatory system have been studied at early stages of the human prenatal ontogenesis in functionally different organs. Ultrastructure of two cell types has been described in the mesenchyme of human embryos. Formation mechanisms of the primary blood vessels belonging to the protocapillary type are revealed. Structural peculiarities of the primary protocapillary network differentiating into various links of the secondary organospecific hemomicrocirculatory bed are distinguished. Certain stageness in development of the microcirculatory system is stated, its blood circulatory compartment including. Two stages are determined in development of the microcirculatory system: prevascular and vascular microcirculation. The latter includes the precirculatory and circulatory phases.     

Adrenal renin: a possible local regulator of aldosterone production

Extrarenal renin has been identified in a number of tissues, including the brain, the submaxillary gland, uterus, ovary, vascular endothelium, testes, pituitary gland, and the adrenal cortex. In some tissues, including the adrenal cortex, all of the components of the renin-angiotensin system have been identified; however, no specific physiologic role has been clearly demonstrated for these extrarenal renin-angiotensin systems. We have studied the role of the renin-angiotensin system in the adrenal cortex of the rat and have found that renin is localized and synthesized in the zona glomerulosa cells. Its production can be influenced by alterations in electrolyte balance, as well as the genetic background of the rat. In adrenal capsular explant cultures, a converting enzyme inhibitor can lower angiotensin II production and reduce the stimulation of aldosterone by potassium, suggesting that this system is involved in the aldosterone response to potassium. In addition to rat adrenals, renin has been identified in human adrenal tissue and human adrenal tumors, including aldosteronomas, and a patient with hypertension has been reported to have an adrenal tumor that appeared to be secreting renin into the circulation.     

Fine structure of, and ACTH production by, human fetal pituitaries taken at different periods of gestation. An in vitro study

Pituitaries were taken from human fetuses between the 6th and 30th weeks of gestation. Organ and monolayer cultures were prepared. The fine structure of the cultures was examined by electron microscopy and their basal and stimulated ACTH release were studied by radioimmunoassay as a function of time in vitro. It was shown that pituitaries taken from the first trimester of gestation have a capacity of self-differentiation; i.e. there was an increase in the number of cells filled with secretory granules and there was an increase in the number of granules per cell. In contrast, pituitaries taken from older embryos have been losing their secretory granules during the cultivation. We failed to demonstrate any corticotropin responsiveness in pituitary cultures prepared from the 6 to 7-week-old embryos. ACTH release could be stimulated from the 10th week of gestation but in slight measure. Pituitary taken from 16-week-old fetuses revealed an adult-like responsiveness to corticotropin.     

Steroidogenic acute regulatory protein expression is decreased in the adrenal gland of the growth-restricted sheep fetus during late gestation

Functional development of the adrenal cortex is critical for fetal maturation and postnatal survival. In the present study, we have determined the developmental profile of expression of the mRNA and protein of an essential cholesterol-transporting protein, steroidogenic acute regulatory protein (StAR), in the adrenal of the sheep fetus. We have also investigated the effect of placental restriction (PR) on the expression of StAR mRNA and protein in the growth-restricted fetus. Adrenal glands were collected from fetal sheep at 82-91 days (n = 10), 125-133 days (n = 10), and 140-144 days (n = 9) and from PR fetuses at 141-145 days gestation (n = 9) (term = 147 +/- 3 days gestation). The adrenal StAR mRNA:18S rRNA increased (P < 0.05) between 125 days (7.44 +/- 1.61) and 141-144 days gestation (13.76 +/- 1.88). There was also a 13-fold increase (P < 0.05) in the amount of adrenal StAR protein between 133 and 144 days gestation in these fetuses. However, the amount of StAR protein (6.9 +/- 1.7 arbitrary densitometric units [AU]/microg adrenal protein) in the adrenal of the growth-restricted fetal sheep was significantly reduced, when compared with the expression of StAR protein (17.1 +/- 1.9 AU/microg adrenal protein) in adrenals from the age-matched control group. In summary, there is a developmental increase in the expression of StAR mRNA and protein in the fetal sheep adrenal during the prepartum period when adrenal growth and steroidogenesis is dependent on ACTH stimulation. We have found that, while the level of expression of StAR protein is decreased in the adrenal gland of the growth-restricted fetus during late gestation, this does not impair adrenal steroidogenesis. Our data also suggest that the stimulation of adrenal growth and steroidogenesis in the growth-restricted fetus may not be ACTH dependent.     

Morphofunctional characteristics of microcirculation in the skin of girls 5-17 years of age

In 261 girls year-to-year morphofunctional transformations of spatial composition of the skin microcirculatory bed have been studied at rest and after a dynamic local load. By means of biomicroscopy main regularities in development of the skin capillary network have been revealed in the nail torus in the postnatal ontogenesis. Formation of the microvessels reactivity during various age periods and maturation of mechanisms of the compensatory-adaptive reactions are connected with formation of the definitive composition of the microcirculatory bed, that in girls corresponds to 11-12 years. Qualitative transformations in the skin capillary network bring certain quantitative changes in the structural microcirculatory parameters--increasing diameter of microvessels and increasing density of functioning capillaries.     

Morphofunctional characteristics of adrenal reactivity in rats of different ages

Ultrastructural peculiarities of the cortical and medullary substance of the adrenals have been studied in mature (8-month-old) and old (26-month-old) intact white male rats and in rats of the same age groups in 3 h after electrical stimulation of the hypothalamic ventromedial nuclei. By means of certain biochemical methods contents of hormones (corticosterone, adrenaline and noradrenaline) have been estimated, as well as that of cholesterin and ascorbic acid in blood and adrenal tissues. After the hypothalamus is stimulated in the mature rats, certain peculiarities in the adrenals reactivity are revealed; they demonstrate positive ultrastructural and functional correlation of secretory cells in the cortex and medulla and are characterized with hypertrophy of the nuclei, increased amount of polyribosomes, hypertrophied Golgi complex and canaliculi of the endoplasmic reticulum and increased contents of corticosteroids and catecholamines in blood. In the old rats after stimulation of the hypothalamus, certain unequal ultrastructural and functional peculiarities are revealed. They demonstrate both disturbance of the hypothalamic regulation of the adrenal function at ageing and decreased adaptive possibilities of the adrenal secretory cells at the subcellular level.     

Development of the neural apparatus of the human pancreas in prenatal ontogeny

In human embryos, prefetuses and fetuses from 6 to 40 weeks of development 82 preparations of the pancreas have been studied; 39 series of slices of the human embryos have been impregnated after Bielschowsky-Boeke. For the first time the nerves grow into the pancreas anlage in embryos of 16 mm long (6 weeks). The main sources supplying the pancreas with the nerves in the period studied are nervus vagus, celiac, hepatic, splenic, right adrenal, superior mesenteric and intermesenteric plexuses. Three stages in formation of the innervational apparatus of the pancreas are distinguished during the intrauterine development. The first stage is characterized by beginning of the nerve growing into the pancreas anlage. For the second stage an increased development of the intraorganic innervational apparatus and appearance of the all main sources of the organ's innervation are specific. The third stage is characterized with an increased differentiation of receptor zones in various parts of the pancreas. The development of the pancreatic innervational apparatus by the time of birth is not completed.     

Sex-related differences in blood and gonad levels of testosterone in silver fox fetuses

The mass of silver fox fetuses of both sexes, their gonads, and adrenals, and the levels of testosterone in blood serum and in gonads and adrenals were determined from day 31 of gestation and every five days thereafter until its termination. Marked sex-related differences were revealed: the blood and gonad levels of testosterone in male fetuses were much higher than those in female fetuses. The fetal adrenals contained significantly less testosterone than the gonads. No sex-related differences in the content of testosterone in the fetal adrenals were found. No differences were found in the body and adrenal mass in female and male fetuses at all the developmental stages studied, while the mass of ovaries exceeded that of testes from day 45 of gestation. The data obtained suggest sex dimorphism in the production of testosterone by gonads in silver foxes appears after day 35 and appears to correspond to the period of morphological differentiation of gonads.     

Morphological evidence for a close interaction of chromaffin cells with cortical cells within the adrenal gland

Summary The adrenal medulla appears to exert a regulatory influence on adrenocortical steroidogenesis. We have therefore studied the morphology of rat, porcine and bovine adrenals in order to characterize the contact zones of adrenomedullary and adrenocortical tissues. The distribution of chromaffin cells located within the adrenal cortex and of cortical cells located within the adrenal medulla was investigated. Chromaffin cells were characterized by immunostaining for synaptophysin and chromogranin A, both being considered specific for neuroendocrine cells. Cortical cells were characterized by immunostaining for 17-hydroxylase, an enzyme of the steroid pathway. Cellular contacts of chromaffin cells and cortical cells were examined at the electron microscopical level. In rat and porcine adrenals, rays of chromaffin cells, small cell clusters and single chromaffin cells or small invaginations from the medulla could be detected in all three zones of the cortex. Chromaffin cells often spread in the subcapsular space of the zona glomerulosa. In porcine and bovine adrenals, 17-hydroxylase immunoreactive cells were localized within the medulla. Single cortical cells and small accumulations of cells were spread throughout this region. At the ultrastructural level, the chromaffin cells located within the cortex in pig and rat adrenals formed close cellular contacts with cortical cells in all three zones. Our morphological data provide evidence for a possible paracrine role of chromaffin cells; this may be important for the neuroregulation of the adrenal cortex.     

Adrenal steroidogenesis in the guinea pig: effects of androgens.

In humans, the onset of adrenache has been found to occur with the appearance of the zona reticularis, the inner zone of the adrenal cortex. Since an increase in the volume of adrenal cortex during maturation in the guinea pig has been associated with the growth of the zona reticularis, we were interested in investigating the changes in adrenal steroidogenesis during maturation in this species. In addition, the effect of androgens on adrenal steroidogenesis was studied. We demonstrated that between 1 and 10 weeks of age, a period of maximal growth of the adrenals in the guinea pig, there is a decrease in the concentrations of adrenal pregnenolone, cortisol, dehydroepiandrosterone, testosterone, androstenedione, and 11 beta-hydroxyandrostenedione, suggesting lower steroid production by the guinea pig adrenals. In plasma, we observed that the concentration of 11 beta-hydroxyandrostenedione (the sole C19 steroid present after castration) remained unchanged during maturation, while cortisol and corticosterone were lower between 1 and 4 weeks of age. Although castration as well as the administration of the antiandrogen flutamide had no effect on adrenal steroidogenesis, dihydrotestosterone caused an inhibition of cortisol and corticosterone levels in the adrenals while the concentrations of progestins (namely, pregnenolone, 17-hydroxypregnenolone, progesterone, and 17-hydroxyprogesterone) tended to increase in the adrenals, thus suggesting that dihydrotestosterone induces a blockade in the steroidogenic pathway.(ABSTRACT TRUNCATED AT 250 WORDS)     

Ultrastructure of the pulmonary trunk wall during the prenatal period of ontogenesis

By means of transmissive electron microscopy stages of morphogenesis have been studied in the pulmonary trunk wall of 12 healthy human embryos and fetuses of 5-24-week-old. There is a close dependence in development of the smooth muscle component of the middle tunic, elastic and collagenous fibers of the pulmonary trunk wall. In the early prenatal morphogenesis of the pulmonary trunk fibrillogenesis develops intensively, overtakes the differentiation time of myocytes from mesenchymal cells, the collagenous fibers appearing earlier than the elastic ones. The structures, that ensure solidity of the vascular wall (collagenous fibers), appear in embryogenesis earlier that those, ensuring its elasticity (ability to reversible deformity).