Week Of Fetal Life Research Articles

Response to rhythmical sound in pre-term infants and term neonates

Abstract Infants born at least 10 weeks before term were compared, when they reached 40 weeks conceptual age, with normal full term neonates on their responses to the rhythmical sound of metronome beats. Crying was significantly reduced in the presence of a 144 beat/m stimulus in term neonates whereas there was no such evidence of pacification among the group born before term. It is suggested that the different environments occupied during the 10 weeks of fetal life preceding the experiment might have contributed to the different responses given by infants in the two groups.

Foregut Cyst Communicated with Esophagus, Lined by Bronchial Mucosa

A case of foregut cyst communicated with esophagus and lined by bronchial mucosa is reviewed and its embryologic base of maldevelopment is discussed. It is not always easy to distinguish between digestive and respiratory cyst in mediastinum. There is whole range of intermediate between a cyst with ciliated and one with squamous or columnar mucosa. Origin of this dysembryoplasia is difficult to determine when one consider that the esophagus is covered with ciliated epithelium until the eleventh week of fetal life and that ciliated growth are found on its wall until the sixth month of the fetal life. And we concluded, general agreement is that cysts which have gastric epithelium in whole or in part, represent a distinct type and should be classified as (gastro) enteric cyst, mediastinal cyst containing cartilage were considered definitely as respiratory(bronchial or bronchogenic) cyst.

Vascularisation des épiphyses en croissance : Le membre supérieur

Sixty fetal, newborn and child cadavers were injected with India ink and plastic material (Batson's technique) via the subclavian artery. The arterial and capillary intracartilaginous and intraosseous networks of the physes of the long bones of the upper limb were then studied by microdissection of the vascular sources and serial epiphyseal sections in different planes. Already present in the third week of fetal life and present all during the rest of life, this circulation plays a fundamental role not only in the ossification of the epiphyseal cartilage but also in the trophicity of the bone that supports the cartilaginous articular surfaces. Like those of the lower limb, the epiphyses of the upper limb present a typical vascular pattern consisting of three entries, with the exception however of the inferior extremity of the ulna.

Hypomastia and mitral-valve prolapse. Evidence of a linked embryologic and mesenchymal dysplasia.

THE pathogenesis of mitral-valve prolapse is unclear. However, it has been associated with thoracoskeletal abnormalities,1 , 2 connective-tissue disorders,3 4 5 and coagulopathies.6 Affected tissues in these disorders are embryologically derived from mesenchymal-cell origins. During the sixth week of fetal life, the mitral valve undergoes embryologic differentiation, and the vertebral column and thoracic cage develop their shape and form through chondrification.7 , 8 The breast, which in large part is of mesenchymal origin, undergoes primordial development during the same time. Since both the breast and mitral valve are of mesenchymal origin, we postulated that an association may exist between breast-size development and mitral-valve prolapse. If present, . . .

Ultrastructure of the human intervertebral disc: II. Cells of the nucleus pulposus.

The cells of the intervertebral disc exist in a unique environment; not only are discs subject to large mechanical loads, they are the largest avascular structures in the body. To describe the ultrastructure and age changes in cells from human nucleus pulposus, we studied these cells in individuals ranging in age from the 26th week of fetal life to 91 years. Viable chondrocyte-like cells existed in specimens from all ages. The presence of Golgi cisternae and well-developed endoplasmic reticulum in these cells suggests that they are capable of producing and maintaining the extracellular matrix. Necrotic cells were also present in all samples, and many cells which appeared viable when examined by light microscopy proved to be necrotic when examined by electron microscopy. The percentage of necrotic cells increased with age from 2% or less in fetal specimens to over 50% in adults. In addition, with age, a distinct pericellular matrix or "nest," consisting of collagen fibrils, fine filaments, dense particles, and banded structures, formed around most cells with no apparent preference for viable or necrotic cells. Nest formation and increasing density of the cell nests may reflect accumulation of cell products.

Ultrastructureofthe human intervertebral disc. I. Changes in notochordal cells with age

We examined nucleus pulposus notochordal cells of individuals ranging in age from the eighth week of fetal life to 32 years of age. With increasing age, notochordal cell structure changed, as did the cell-to-cell relationships and the cell-to-matrix relationships. All notochordal cells contained normal organelles, including welldeveloped endoplasmic reticulum, but, in addition, fetal notochordal cells demonstrated an unusual relationship between rough endoplasmic reticulum and mitochondria: elements of the rough endoplasmic reticulum encircled almost every mitochondrion. Fetal notochordal cells contained large amounts of glycogen, while older cells had much smaller glycogen deposits. Cytoplasmic filaments were observed in cells of all ages. The cells formed tightly packed clusters in the fetus with little, if any, extracellular matrix between individual cells. Cells separated from each other with age and by the twenty-first week of fetal life, only slender strands of cytoplasm connected them. Previous light microscopic studies described notochordal cells as ‘physaliphorus’ cells since they appeared to contain large cytoplasmic vacuoles. However, electron microscopy showed that these apparent vacuoles consist of extracellular matrix surrounded by cells or cell processes. The structure of notochordal cells and their persistence in the nucleus pulposus after fetal life suggest that they may have a significant role in the formation and maintenance of the nucleus pulposus.

Quantitation of the B and A cell fractions in human pancreas from early fetal life to puberty

The morphological development of B and A cells in human pancreas was studied with immunoperoxidase stains in 172 cases ranging in age from 12 weeks of fetal life to puberty. Tissue was defined as polypeptide rich or poor to take account of the known islet heterogeneity in the gland. Pancreatic cell density was measured and B and A cell development was calculated in terms of (a) volume fraction and (b) density (μm 2/100 nuclei). B cell density increased throughout fetal life to reach a peak at the postnatal age of 2 months, whereas A cell density was greatest in the 6 month fetus. The ratio of B to A cell volume fractions is approximately 1.5 throughout most of fetal life and rises postnatally to a stable value of 5 by the age of 2.5 years.

Developmental study on the facial nerve and canal in man (author's transl)

The development of the facial nerve and its canal in the temporal bone was histologically investigated with serial sections in connection to the middle ear sugery.Materials used were 56 Japanese human embryos and fetuses aged from the 4th to the 23rd week (3.3 to 330mm in CR or CH length) that were stored in the Human Embryo Center for Teratological Studies of Kyoto University and Department of Otolaryngology, Okayama University Medical School. The results were as follows:1) The second arch epibranchial placode seemed to play an important role in the development of the geniculate ganglion.2) A trunk of the facial nerve, chorda tympani nerve and N. petrosus major accomplish before the ossicles appeared at the 6th week.3) The facial nerve was rapidly differentiated as the internal meatal, horizontal and vertical segments as with the development of the primordial stapes at the stage 17 and was gradually completed its normal running course by both the differentiation of the cartilagenous otic capsule and the pneumatization of the primitive tympanic cavity during the whole intra-uterine period.4) The development of the facial canal began as a sulcus on the canalicular division of the precartilagenous otic capsule at the stage 21. The formation of the tympanic boundary of the horizontal segment until the 22nd week of fetal life.5) Anson's hypothesis in which the head of malleus and the body of incus are made from Meckel's cartilage, and the handle of malleus and the long process of incus from Reichert's cartilage was supported.6) The rate of the thickness of the facial nerve to the diameter of the facial canal was large at the horizontal segment, but it was small at the vertical segment.

Human Ontogenesis

The ultrastructural pattern of the early stages of end-plate formation is described in the quadriceps femoris muscle of 9- to 20-week-end human fetuses. Features of the neuromuscular junction are first observed in the ninth week of fetal life. The primitive motor end-plate contains a few axons always covered by one Schwann cell and does not seem to change either in number or in structure from the tenth through the twentieth week. Continuous modification of the post-synaptic apparatus is observed from the tenth to the twentieth weeks of human fetal life.

Biochemistry of sexual development unfolding

Mammalian sexual development is delicately controlled, particularly during certain critical periods of early fetal development. Slight biochemical mishaps at such times can be magnified and often distorted, thereby leading to abnormal anatomy and possibly also to abnormal behavior. The scientific basis for such abnormalities is emerging both from controlled laboratory studies of simple mammals such as rats and mice and from clinical studies on man. Progress in understanding the underlying biochemistry was reviewed at a recent meeting held in New York and sponsored by the Endocrine Society. Although an individual's sex is determined at conception, for humans sexual traits do not begin to appear until after the 12th week of fetal life. Then, a highly ordered process of development begins that depends on a surprisingly small number of enzymes and hormones. Any slight shift in their activity and behavior can have profound consequences, according to Jean D. Wilson, director of ...

The MURCS association: Müllerian duct aplasia, renal aplasia, and cervicothoracic somite dysplasia

Two patients and 28 others in the literature were ascertained because of congenital vaginal agenesis associated with clinical and/or radiographic evidence of malformations derived from the cervicothoracic somites. In these patients, there was a high incidence of Müllerian duct aplasia/hypoplasia (96%), renal agenesis and/or ectopy (80%), and abnormalities related to cervicothoracic somite dysplasia, particularly 2 to 4 anomalous vertebrae located between C5-T1 (80%). These consistent findings suggest a distinctive non-random association of malformations: Müllerian duct (MU) aplasia, renal (R) aplasia, and cervicothoracic somite (CS) dysplasia (MURCS). Identification of one component of the MURCS association suggests the presence of the other associated anomalies. A hypothesis for the embryogenic pathogenesis of the MURCS association is proposed which attributes the malformations to an alteration of the blastemas of the lower cervical-upper thoracic somites, arm buds, and pronephric ducts, all of which have an intimate spatial relationship at the end of the fourth week of fetal life. A presently unidentified teratogen may be one of the possible causes of the MURCS association on the basis of a lack of familial transmission, normal chromosomal studies, and the similar effects of a known teratogen (thalidomide) on the developing genitourinary tract.

Infundibular neurons of the human hypothalamus simultaneously reactive with antisera against endorphins, ACTH, MSH and ?-LPH

In man, discrete neurons of the infundibular (arcuate) nucleus contain compounds that can be stained with anti-endorphin (alpha and beta), anti-ACTH, anti-MSH (alpha and beta) and anti-beta-LPH immune sera (I.S.). In the fetus, certain neurons stain with anti-beta-endorphin or anti((17--39)ACTH starting from the 11th week of fetal life. At the ultrastructural level, these neurons contain elementary granules that are immunoreactive with anti-beta-endorphin. In the adult, neurons immunoreactive with anti-beta-endorphin are found in the infundibular nucleus. Their axonal fibers terminate around blood vessels in the neurovascular zone and in the pituitary stalk, or establish contacts with non-immunoreactive perikarya of the infundibular nucleus. These neurons can be stained with anti(17--39)ACTH and anti-beta-endorphin I.S. The most reactive are also stained moderately with anti-alpha-MSH, anti-beta-MSH, anti-beta-LPH, anti-alpha-endorphin, or anti(1--24)ACTH I.S. These results indicate that, in man, compound(s) identical with or immunologically related to endorphins, beta-LPH, ACTH and MSH are secreted by certain hypothalamic neurons. These agents probably originate from a common precursor molecula similar to the so-called pro-opiocortin.

Immunologie localization of ?- and ?-endorphins and ?-lipotropin in corticotropic cells of the normal and anencephalic fetal pituitaries

The use of antibodies to alpha-(17--39) ACTH, beta-LPH, and alpha- and beta-endorphins has enabled the detection of immunoreactive cells as early as the eight week of fetal life. Immunoreactive cells are located in the anterior and intermediate lobes of the pituitary gland in normal human fetuses. The same cells reacted with different antisera used in the present study. No immunoreactive cells were observed in the posterior lobe. The specificity of the immunocytological reaction has been controlled. In seven anencephalic fetuses, the presence of immunoreactive cells suggests that ACTH and beta-LPH can originate from a common precursor and are synthesized independent of the hypothalamus.

Origin of the calvaria and its sutures.

Studies indicate that the dura is the guiding tissue in the morphogenesis of the calvaria and its major sutures, which develop from ten to 16 weeks of fetal life. Overlying the central zones between the dural reflections ossification takes place, whereas none occurs over the reflections of dura, these being the suture sites. Strong evidence for the role of the dural reflections in determining the suture sites was obtained from the evaluation of instances of major brain malformations that must have antedated calvarial morphogenesis. These included holoprosencephaly, craniopagus, and dicephaly. The altered dural reflections, which related to the aberrant form of the brain, coincided with the position of the unusual sutures. Furthermore, a lack of a dural reflection was accompanied by a lack of development of a suture at that site.

PRENATAL DIAGNOSIS OF HOMOZYGOUS FAMILIAL HYPERCHOLESTEROLÆMIA: Expression of a Genetic Receptor Disease in Utero

Cultured amniotic-fluid cells from a fetus at risk for homozygous familial hypercholesterolæmia (F.H.) almost completely lacked cell-surface receptors for plasma low-density lipoprotein (L.D.L.), as evidenced by direct measurement of binding, uptake, and degradation of 125I-L.D.L. Functional consequences of L.D.L. binding to the receptor—i.e., suppression of 3-hydroxy-3-methylglutaryl coenzyme A reductase and stimulation of cholesterol esterification—were proportionately reduced when compared with results in cultured amniotic cells from two control fetuses. On the basis of these findings, homozygous F.H. was diagnosed and the pregnancy was terminated at the 20th week. The diagnosis of homozygous F.H. was confirmed by a serum-cholesterol of the aborted fetus of 279 mg/dl, a value 9 times the mean of four control fetuses of similar gestational age. More than 80% of the serum-cholesterol of the affected fetus was contained within L.D.L. Prenatal diagnosis of homozygous F.H. now seems practical; moreover, the finding of a raised serum-L.D.L. in the affected fetus indicates that the L.D.L. receptor is normally functional as early as the 20th week of fetal life.

Immunocytochemical study of the ontogenesis of the hypothalamic somatostatin-containing neurons in the human fetus.

Immunocytochemical techniques have enabled us to characterize the hypothalamic somatostatin system in the human fetus and to study its ontogenesis. Somatostatin-containing neurons appear as early as the 16th week of fetal life. Their perikarya belong to two distinct cell populations: some of them, of large size, form clusters in the magno-cellular nuclei (S.O.N.-P.V.N.); they seem to be neurophysin-positive. The others, parvo-cellular, lie scattered in ventral periventricular areas; they are neurophysin-negative. Most of the immunoreactive fibers pass through the M.E. and terminate in two distinct territories: on the one hand close to the vessels of the primary portal plexus (these territories being neurophysin-negative) and on the other hand, in the peripheral regions of the neural lobe (these territories being neurophysin-positive). The staining reactions obtained with the anti-somatostatin and anti-neurophysin I.S. suggest the existence of 2 hypothalamic somatostatin systems. The former (neurophysin-negative) which appears to originate from the parvocellular perikarya and which terminates in the M.E., controlling adenohypophyseal cells, the latter (neurophysin-positive) originating from one of the S.O.N. and P.V.N. cell populations appears to terminate in the neural lobe. The existence of the latter system suggested by the results of the present and the preceding studies on other species has yet to be fully established.

Cyto-immunological study of the ontogenesis of the gonadotropic hypothalamo-pituitary axis in the human fetus

Using anti-LH-RH immune serum, LH-RH producing neurons were characterized in the hypothalamus from the 13th week of fetal life up to birth. The immunoreactive perikarya are concentrated in mediobasal, premammillary and anterior hypothalamus (lamina terminalis and rostral commissure region) and their axons contribute to the tubero infundibular tract. They terminate close to the blood vessels of the Mantelplexus before and after the apparition of the intra eminential loops (at the 16th week); immunoreactive fibres terminate also around the capillaries of the vascular organ of the lamina terminalis and near ependymal epithelium. In the pituitary, gonadotropic and thyrotropic cells were immunocytologically demonstrated by anti-FSH absorbed with-HCG and LH, and anti-LH, anti-HCG and anti-TSH absorbed or not with α LH. Only α subunits were identified from the 8th to the 12th week. From the 13th week, β TSH subunits appear in the thyrotrophs. From the 15th week, β FSH and β LH subunits responsible for biological activity were revealed in the same gonadotropic cells; the role of the human fetal hypothalamus in the differentiation of gonadotropic cells is discussed.

ORIGIN OF CALVARIAL SUTURES IN RELATION TO DURAL REFLECTIONS: NORMAL DEVELOPMENT AND PREDICTABLE ALTERATIONS SECONDARY TO BRAIN MALFORMATION

Studies of normal calvarial morphogenesis in human fetuses were found to support the concepts of Tondury and of Moss. The early growth and form of the brain causes growth stretch on the dura with the development of reflections which extend from the sites of dural attachment at the cranial base and conform to the major recesses in the early brain. The dura is the guiding tissue in the morphogenesis of the overlying calvarium and its major sutures, which develop from 10 to 16 weeks of fetal life. In the quiet zones between the dural reflections ossification occurs, whereas over the reflections of dura no ossification occurs, these being the sites of sutures. Supportive evidence for the role of the dural reflections in determining the sites of sutures was obtained from the evaluation of instances of major brain malformations which must have antedated calvarial morphogenesis. These included holoprosencephaly (13 cases), craniopagus (7 cases) and dicephaly (2 cases). In each case the gross brain malformation gave rise to unusual sites of dural reflection, which were found to coincide with the unusual sites of sutures in the calvarium. Furthermore, a lack of a dural reflection was accompanied by a lack of development of a suture at that site. The relevance of these findings to the evaluation of problems of brain morphogenesis and the diagnosis and management of craniostenosis will be discussed.

The stilbestrol-adenosis-carcinoma syndrome.

This disease complex is one of the few entirely new and previously unsuspected discoveries of the recent past. The first case, seen in 1966, ushered in an era of suspicion. A study and report on the first seven cases published in 1970 inaugurated the era of hot pursuit which culminated in 1971 in an epidemiologically structured and controlled investigation of possible etiologic factors. With the establishment of the stilbestrol association a Registry of Cases was initiated. , heralding the era of verification. This Registry, while accelerating and embossing confirmation of the suspected relationship, served an even more useful purpose by collecting under one roof and in front of one cluster of observers all the necessary and relevant data on a sufficiently large number of cases to enable rapid (1973-1974) wide dissemination of knowledge about the occurrence and behavior of the disease and its response to treatment. The behavior of these tumors is comparable to that of other cancers at this location. When they are still localized, cure is possible by either surgery or radiation therapy. Since all the individuals at risk can be identified by their clinical history, screening examination for presymptomatic cancer is entirely feasible. At the same time we can and should note the presence and nature of any morphologic anomalies of the kind, which are seen in a very high proportion of the women exposed before the 18th week of fetal life.

Sexuality and endocrine glands

In the fifties, Jost, the French endocrinologist, on the basis of his research concluded that the theory of the Bi-sexual phase of the initial embryonic existence is incorrect. He discovered that the early embryo is not undifferentiated, it is differentiated. It is a female. In the beginning we were all created females. Genetic sex is established at fertilization, but the influence of the sex genes is not brought to bear until the fifth to the sixth week of fetal life. The process is as follows: 1. If the genetic sex is female, the germ cells migrate to the gonadal cortex. There, the ovaries are formed and fetal estrogen is eventually produced. However, if for some reason the ovaries would not develop, the fetus will still be a female although with abnormalities. Consequently, the development of the female is autonomous, nothing has to be added. 2. If the genetic sex is male, the primordial germ cells migrate from the endoderm of the yolk sac, to the gonadal medulla. There, the germ cells stimulate the production of a testicular inductor substance which subsequently stimulates the elaboration of the fetal androgen. Androgen suppresses the growth of the oviducts and gonadal cortex, and induces the growth of the internal and external male genital tract. 3. Genetic sex is not the only factor assuring the physical development of a sexually normal individual. There must be an optimal amount of hormones. The hormones must be properly metabolized. In the genetic male, there must not develop an immunity toward androgens. Equally important is the normal amount and normal configuration of the sex chromosomes. 4. To produce a male, androgenic steroids must start to function at the critical period of development. They will have a decisive influence on the