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Histochemical and radiologic studies of the human fetal mandibular condyle.

Histochemical investigations on the mandibular condyle were performed on 72 human embryos and fetuses of crown-rump lengths (CRL) ranging from 26 to 186 mm, representing skeletal maturity indices expressed in CNO values (CNO = composite number of ossified bones in the hand and foot) ranging from 0-0 to 19-12. The development of the mandibular condyle is described according to morphology and to histochemical reactions for glycosaminoglucuronglycans, collagen, glycogen, alkaline and acid phosphatase, and nonspecific AS esterase. The development is described for (1) the bony component of the mandibular condyle, (2) the condylar cartilage, and (3) the fibrous cover of the mandibular condyle. For each tissue component, maturation steps are set up and included in the total evaluation of the condylar maturity stages. The developmental sequence set up on the basis of the morphologic and histochemical findings was followed by all condyles investigated. From this it may be presumed that the developmental sequence in human mandibular condylar components is constant during the former half of the prenatal period. The material available did not justify a description of skeletal development in the mandibular condyle as a function of fetal size, CRL, or skeletal maturity in the hand and foot.

Alkaline Phosphatase↗

Pineal serotonin metabolism in non-innervated perinatal glands before and after intraocular maturation: supersensitivity of adrenoceptors that have never been innervated.

Transplantations were made of fetal pineal glands (crown-rump length, CRL, 19-30 mm) or pineal glands from adult male rats to the anterior chamber of the eye of the rat. Studies were performed with regard to the importance of the age of the donor animal (and thereby the degree of maturation and innervation of the gland to be transplanted) for the possible development of denervation supersensitivity. The transplants were cultured in a medium containing 14C-serotonin. Increased production of 14C-N-acetylserotonin (NAcS) was used as the main criterion for beta-adrenergic stimulation. 4 experimental groups were obtained by transplanting fetal or adult pineals to intact or sympathetically denervated eyes. In all 4 groups beta1-stimulation (KWD 2033 10(-6) M) increased 14C-NAcS formation. The response to beta-stimulation was significantly higher in denervated fetal pineal transplants than in innervated fetal transplants and thus demonstrating beta-receptor supersensitivity. It was concluded that a) the ability to respond to beta-adrenoreceptor stimulation with increased 14C-NAcS formation develops between the 18th and 20th day of gestation, b) transplants derived from fetal as well as from adult rats can respond to beta-adrenergic stimulation, c) this sensitivity also develops in oculo in transplants that at the time of transplantation lacked the capacity to increase their 14C-NAcS formation in response to treatment with beta-agonist, d) denervation supersensitivity occurs in fetal transplants that became mature in sympathetically denervated eyes.

Animals↗

Immunoglobulin-bearing lymphocytes: their demonstration in adult sheep and ontogeny in the sheep fetus.

A method for the preparation of lymphocytes from sheep blood is described. Lymphocytes from adult and fetal sheep have been examined by immunofluorescence for surface immunoglobulin (sIg) determinants. Young adults (1.5 years) had a mean of 23.2% sIg cells, older adults (8.75 years) a mean of 9.7% sIg cells. Pregnancy did not influence these values. The earliest lymphocytes with sIg in fetal lambs were demonstrable at 52 days (96 mm crown-rump length) and countable by 56 days (110 mm CRL) at 0.3% sIg. The percentage rose rapidly to 15.1% between 78 and 87 days, followed by a fall to 2.1% around 117 days with a second increase thereafter. The significance of this spontaneous appearance of fetal sIg cells is discussed.

Aging↗

Embryotoxic effects of polybrominated biphenyls (PBB) in rats.

Pregnant Sprague Dawley rats were given 0, 0.25, 0.5, 1, 5, and 10 mg of a commercial polybrominated biphenyl, FireMaster BP-6 (PBB), in olive oil by gavage each day from days 7 through 15 of pregnancy. Laboratory chow and water were given ad libitum. Treatment with PBB had no significant effect on body weight gain, food and water consumption, and urine production. The mothers were killed on day 20, and the only significant effect observed was an increased liver weight of those given 1, 5, and 10 mg PBB. Spleen, kidney, ovarian, gravid uterine, and perirenal fat pad weights were similar to those of control mothers. PBB had no significant effect on number of live/dead fetuses, crown-rump length or fetal weight. No grossly malformed fetuses were observed in PBB-treated mothers. The effects of PBB transfer from mothers to nursing pups was studied by reciprocal exchange of pups between control mothers and mothers treated with 10 mg PBB. When the pups were 21 days old, they were weaned and fed control chow. The following four combinations of prenatal-postnatal exposure were studied: control-control (C:C); control-PBB (C:PBB); PBB-control (PBB:C); and PBB-PBB. Although the birth weights of pups from PBB-treated mothers were similar to those of the controls, body weights of 60-day-old males exposed prenatally and postnatally (PBB:C, C:PBB, and PBB:PBB) were less (p less than 0.05) than those of the controls (C:C). The weights of the perirenal fat pads of male and female pups exposed to PBB were less (p less than 0.05) than the control. Liver weights, on a body weight basis, were higher in male and female pups exposed to PBB. Vaginal openings were delayed; the percentages of 36-day-old pups with open vaginas were 50 (C:C), 38 (PBB:C), 28 (C:PBB), and 30 (PBB:PBB).

Animals↗

The development of vertebral bone marrow of human fetuses.

The development of the bone marrow of the thoracic vertebrae in seven human fetuses ranging from 95 to 150 mm in crown-rump length (CRL) was studied using light and electron microscopy. In the 95-mm CRL, hypertrophy of the chondrocytes occurred in the central region of the vertebrae, and blood vessels penetrated there from dorsal and ventral sides of the vertebral body. The primary marrow was represented by liberated cartilage lacunnae, occupied by the thin-walled blood vessels and a few mesenchymal cells and mononuclear cells containing granules or vacuoles (GMC). In the 99-mm CRL, chondroclasts were active in removing the cartilage near the central region of the vertebrae. Consequently, a large cavity was formed and occupied by a dilated sinus. GMC were numerous. Osteoblasts and osteocytes were increased in number. Reticular cells with long processes containing large amounts of glycogen began to appear in the extravascular space and formed the loosely arranged cellular meshwork of the hematopoietic compartment. Bundles of collagen fibrils were scattered in the meshwork. Hematopoietic cells were recognizable only in the 105-mm-CRL fetus and increased in number in the 120-mm-CRL fetus. The sinus endothelium was very thin and continuous without apertures except where blood cells crossed the wall. The developing blood cells lying against the outside of the sinus endothelium indented it. At points, collagen fibrils attached to the outside of endothelial cells and appeared to function as the anchoring filaments of lymphatics. The physiologic implications of the association of stromal cells, vascular sinuses, and hematopoietic cells are discussed in relationship to the microhematopoietic environment of the bone marrow.

Bone Marrow↗

The growth and development of the squirrel monkey (Saimiri Sciureus).

Squirrel monkeys of 2 subspecies, Bolivian and Colombian, were removed from their mothers on the day of birth and nursery reared for up to 2 years of age. Infants were tested weekly for 12 weeks, then monthly for 1 year, and at 2 years of age. Tests included morphology (body weight, crown-rump length, and head measurements), behavior (reflexes, activity, reaction to the surrogate), and physiology (heart rate, respiratory rate, temperature and optokinetic nystagmus). Data show some likenesses and some differences between the 2 subspecies.

Animals↗

Histological development of stapes footplate in human embryos.

Normal development of the human stapes footplate was investigated in serial sections by light microscopy. Materials were obtained from 35 Japanese embryos from the 6th to 32nd week of embryonal age. Eighteen embryos up to 16 weeks of age (3.5mm to 105mm in crown-rump length) were examined, focusing particularly on the lamina stapedialis of the otic capsule. The present study showed that primordial formation of the lamina stapedialis appeared in 16mm embryo and that the lamina was completely formed and fused to the base of the annular stapes in a 35mm embryo. In a 50mm embryo, the adult form of stapes was found with a rim and annular ligament. The results, therefore, seemed to essentially agree with the theory of dual origin and development of the footplate proposed by Cauldwell and Anson, and teratogenic agents might affect any stage of the process producing anomalies, including congenital footplate fixation, congenital absence of the oval window and calcification of the annular ligament.

Ear Ossicles↗

Peptidergic (VIP) innervation of the esophagus.

Nerves displaying vasoactive intestinal polypeptide (VIP) immunoreactivity were demonstrated in the esophagus of rats, cats, and pigs. Furthermore, electron microscopy revealed the presence of nerve terminals displaying the features of peptidergic nerves. VIP nerves were abundant within the smooth muscle layer of the lower esophagus of cat and pig. Immunoreactive nerve fibers and nerve cell bodies were found in the plexuses of the esophageal wall. In pig fetuses VIP immunoreactive nerve cell bodies were observed already at crown-rump length of 4 cm. VIP nerves were also observed in human fetal esophagus. For recording of the motor effects of VIP, segments were taken from cat esophagus close to the esophagogastric junction. VIP induced a dose-dependent relaxation upon contraction by carbamylcholine.

Animals↗

Changes in axonal numbers in developing human trochlear nerve.

Complete axonal counts have been made in the intracranial parts of trochlear nerves from human fetuses of 9.2, 10 and 24 cm crown-rump length. A count was also made in the intraorbital part of the nerve from the 10 cm specimen. Schwann cell nuclei were also counted in typical cross sections, but do not necessarily reflect very accurately the schwann cell contents of the nerves. Axonal numbers conform to the propositions (1) that they do not all grow out at once, (2) do not all survive and (3) that degeneration may occur before or after myelination has begun. It seems inevitable that some loss of Schwann cells occurs in relation to the degeneration of myelinated axons, but there is no evidence for or against such a loss in relation to the degeneration of unmyelinated axons. Overall, however, Schwann cell numbers tend to increase as the number of myelinated axons increases.

Axons↗

Muscular development of the bladder neck in the human fetus.

We conducted a histologic study of the muscular development of the bladder neck in human fetuses of 5 to 23 cm crown-rump length (CRL) and in neonates in special reference to the middle circular layer of the posterior wall of the bladder neck (posterior circular muscle of the bladder neck) and the deep trigonal muscle. Our attempt was to determine the anatomic relationship between and the origins of the two musculatures. The posterior circular muscle had begun to differentiate in the fetus of 8.3 cm CRL in which the trigonal musculature was indistinguishable. Differentiation of the deep trigonal musculature was evident in the fetus of 17 cm CRL; a complete growth in which the muscle was connected to the posterior circular muscle of the bladder neck was evident only in the largest fetus (23 cm CRL). We conclude that the deep trigonal muscle and the posterior circular muscle of the bladder neck are of different origins.

Gestational Age↗

Palatal shelf elevation in the Wistar rat fetus.

Palatogenesis in the Wistar rat fetus was studied macroscopically, microscopically, ultrastructurally and experimentally between days 13 and 19. The developmental ages of the fetuses were calculated from the smear age of the litter adjusted for individual variations in crown-rump lengths. Palatal shelf elevation occurs at day 16.4 +/- 0.1. Experimentally induced shelf elevation in freshly delivered fetuses was sluggish at day 14, but by day 16.3 it occurred in less than 1 second. Both shelf elevation and shelf fusion begin anteriorly where the shelves show a marked convexity of their margins, and proceed posteriorly. The extreme posterior part of each shelf (future soft palate) is horizontal from the beginning. The matrix of the shelf mesenchyme (especially in the region of the anterior convexities) shows an increasing accumulation of mucopolysaccharides from day 14 to day 16.3 and becomes increasingly oedematous. The shelf attachment to the main maxillary process is progressively undercut by epithelial invagination, producing a fulcrum for shelf elevation. The maxillary and palatine osteogenic blastemata are present at the base of the shelf prior to elevation and rapidly invade the shelves after the event. The elevated palatal shelves fuse with the nasal septum anteriorly, but posteriorly the palate is not attached to the septum. The posterior septum at first has a free lower edge, but then it develops lateral flanges which fuse with corresponding bulges on the lateral nasal walls. In this way two sphenoethmoidal recesses are formed above the fused flanges, while a common nasal passage is formed above the palate, roofed anteriorly by the septal flanges and posteriorly by the cranial base. The space needed to create (simultaneous with shelf elevation) the common nasal passage is made available by flattening of the tongue and protrusion of its tip out of the oral cavity--this protrusion being facilitated by the sloping bulge of the primary palate and nasal septum. Many existing theories of shelf elevation are inconsistent with these observations. It was concluded that shelf elevation occurs very rapidly at a rather precise developmental stage and that turgor (due to binding of water to mucopolysaccharides) is the intrinsic force which elevates the shelves, a force which at 16.4 days reaches a threshold level enabling the shelves to force their way up and over the intervening tongue.

Animals↗

Milk protein quantity and quality in low-birthweight infants: I. Metabolic responses and effects on growth.

The optimal quantity and quality of protein for low-birthweight infants is undefined. In this study, 106 well, appropriate-for-gestational age, low-birthweight infants weighing 2,100 gm or less were grouped in three gestational age categories: T1 = 28 to 30 weeks; T2 = 31 to 33 weeks; T3 = 34 to 36 weeks. Each group was assigned randomly to either banked human milk (BM) or to one of four isocaloric formulas varying in quantity and quality of protein but not in mineral content or in fat content: formula 1 = 1.5 gm of protein per 100 ml, 60 parts bovine whey proteins to 40 parts bovine caseins; formula 2 = 3.0 gm of protein per 100 ml, 60:40; formula 3 = 1.5 gm of protein per 100 ml, 18:82; formula 4 = 3.0 gm of protein per 100 ml, 18:82. Caloric intake was 117 kcal/150 ml/kg/day for the formulas. Human milk was fed at 170 ml/kg/day in order to attain a caloric intake approximately equal to that of the formulas. No significant differences were found in the rate of growth in crown-rump length, in femoral length, in head circumference, or in rate of gain in weight from time of regaining birthweight to time of discharge at 2,400 gm. Blood urea nitrogen, urine osmolarity, total serum protein, serum albumin, and serum globulin varied directly with the quantity of protein in the diet: F2, F4 greater than F1, F3 greater than BM. Blood ammonia concentration varied with both quantity and quality of protein in the diet: F2, F3, F4 greater than F1, BM. Metabolic acidosis was more frequent, more severe, and more prolonged in the infants fed the casein-predominant formulas (F3,F4) than in those fed the whey protein-predominant formulas (F1, F2).

Ammonia↗

[The effect of glucocorticosteroids on sex differentiation in rats].

The influence of two glucocorticoids (hydrocortisone and dexamethasone) on the somatic sex differentiation of female rats was investigated. During the time of sexual differentiation of their foetuses, pregnant rats were given dexamethasone (0.1-0.3 mg/day) or hydrocortisone (20-200 mg). Both compounds interfere with foetal development by virtue of their strong growth-inhibitory activity which manifests itself in reduction of the body weight, the crown-rump length, the length of the genital folds and the genital cord. The inhibition of growth seems to be reversible. Only hydrocortisone acts teratogenically as it causes a shift of the differentiation of the female genital tract into male direction. This virilisation consists of partial stabilisation of the Wolffian ducts, the suppression of mammary nipple development and a male-type differentiation of the urogenital sinus. The relevance of these findings for human beings is briefly discussed.

Animals↗

Experimental amniocentesis and teratogenesis. 1. Evaluation of the intra-amniotic route of treatment in teratological studies.

Experiments were designed to evaluate the usefulness of the intra-amniotic route of administration of test-substances in teratological studies. Particular attention was given to the differences in fetal parameters of growth and development and the incidence of fetal mortality between treated and untreated offspring which might be induced as a result of the treatment. Amniocentesis on gestational days 14, 15 or 16 produced a high incidence of fetal mortality and a significant reduction in the weights and crown-rump lengths of treated offspring. With increasing gestational age at the time of treatment and by reducing the volume of solvent injected, fetal mortality was decreased.

Amnion↗

Electron microscopy of the early embryonic development of the human corneal epithelium.

The eyes of a human embryo in the 6th week, 11 mm crown-rump (C.R.) length, and of a human embryo in the 7th week, 19 mm C.R. length, were examined. In the embryo of 11 mm C.R. length, the lens vesicle had just detached from the surface ectoderm, the presumptive corneal epithelium. The acellular primary corneal stroma appeared between the lens vesicle and the overlying ectoderm. The fine structure of the ectodermal cells, of their basal lamina, and of the primary stroma is described. In the embryo of 19 mm C.R. length, mesenchymal cells had moved from the periphery into the space between the ectoderm and the lens. There were remarkable changes in the structure of the corneal epithelial cells, in their basal lamina, and in the underlying substances of the primary stroma.

Cornea↗

Estimating the age of the human foetus from crown-rump measurements.

When data from various sources were compared, it was found that estimates of foetal age based upon crown-rump measurements varied considerably. These variations are probably related to the positions in which the foetuses were measured. Tables relating foetal age to foetal length should therefore specify the precise posture in which the foetus was placed for measurement. A standard readily reproducible position is proposed for the foetus when recording its length and it is suggested that crown-rump length should be related to "conceptual" age instead of the more conventional "menstrual" age.

Anthropometry↗

Development of the omasum in sheep.

Data are presented on the histogenesis of the omasal mucosa in sheep from the 2.5 cm crown-rump (c-r) length fetus to the adult. 11 stages of fetal development, and 4 post-natal stages, were studies. The distribution of glycogen in the omasal epithelium was also studied. During fetal life the omasal epithelium was initially stratified cuboidal in type, but the superficial layers of cells became flattened in later stages of gestation. This epithelium became extremely thick by the late stages of fetal life, reaching a maximum of 358 micron, and consisting of greater than 20 layers of cells, in the 45 cm c-r fetus (approximatelay 140 days). After birth the epithelium became markedly reduced in thickness, being approximately 77 micron in the adult, and had differentiated into a cornified stratified squamous epithelium of the adult type by 12 weeks after birth. Glycogen was extremely abundant in the omasal epithelium of the 2.5 cm fetus, and declined gradually thereafter to be almost completely absent in post-natal specimens. 4 orders of laminae were present in the adult omasum, distributed in the seqeunce 1-4-3-4-2-4-3-4-1. The 1st order was already present in fetuses of 2.5 cm c-r length, with the 2nd, 3rd and 4th appearing by the 3.5, 5.5 and 11.0 cm stages, respectively. Initial stages in the development of conical papillae were first seen in 15.0 cm fetuses, but the development of these papillae was not completed until after birth.

Age Factors↗