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PubMed2000

Myocardial growth before and after birth: clinical implications.

Perinatal changes in myocardial growth have recently evoked considerable interest with regard to cardiac chamber development with congenital cardiac lesions and to myocardial development in preterm infants. It is suggested that cardiac chamber development is influenced by blood flow. Experimental pulmonary stenosis in fetal lambs may induce either greatly reduced or markedly increased right ventricular volume. Ventricular enlargement appears to be associated with a large ventricular volume load resulting from tricuspid valve regurgitation. A small competent tricuspid valve is associated with reduced flow through the ventricle due to outflow obstruction and a small right ventricle. Postnatal growth of the ventricles in congenital heart disease is discussed. Increase in myocardial mass prenatally is achieved by hyperplasia, both during normal development and when myocardial mass is increased by right ventricular outflow obstruction. Postnatally, increases in myocardial mass with normal growth, as well as with ventricular outflow obstruction, are largely due to hypertrophy of myocytes. Myocardial capillary numbers do not increase in proportion with myocyte numbers in ventricular myocardium in association with outflow obstruction. The postnatal effects of these changes in congenital heart lesions are considered. Studies in fetal lambs suggest that the late gestational increase in blood cortisol concentrations is responsible for the change in the pattern of myocardial growth after birth. The concern is raised that prenatal exposure of the premature infant to glucocorticoids, administered to the mother to attempt to prevent hyaline membrane disease in the infant, may inhibit myocyte proliferation and result in a heart with fewer than normal myocytes. This would necessitate that each myocyte would have to hypertrophy abnormally to achieve a normal cardiac mass postnatally.

Adrenal Cortex Hormones↗
PubMed1998

Intrauterine growth acceleration in the case of a severe form of mucopolysaccharidosis type VII.

We describe a Japanese male infant with mucopoly-saccharidosis type VII (MPS VII) who was born at 32 weeks of gestation presenting as a non-immune hydrops fetalis. His birth weight was 2900 g (+4.1 SD), his birth length was 48 cm (+2.2 SD), and thoracic spine length was 9.5 cm (+2.7 SD) at birth. Ossification center was already discernible bilaterally in coracoid process and distal femur at birth. In eight newborn infants with fetal hydrops of various other etiologies born in our institution, birth length ranged from -0.2 to -1.5 SD and thoracic spine length ranged from +0.5 to -1.7 SD, and neither ossification center of coracoid process nor distal femur were visible. The above data indicate that hydrops fetalis form of MPS VII is associated with intrauterine growth acceleration accompanied by early bone maturation. This feature may be useful in differentiating MPS VII associated hydrops fetalis from those of other etiologies.

Bone Development↗
PubMed1986

The fetus in the extrauterine environment.

The influence of environmental factors on early development is discussed beginning with studies on the preterm newborn, most of which compare preterms who have reached 40 weeks conceptional age with full term newborns in respect of neuropsychic development. They are therefore open to several methodological criticisms and have supplied often contradictory results. With ultrasound techniques it is now possible to compare the fetus with the preterm in respect of motor development at the same conceptional age. The variety of methods used and the limits of fetal observability, especially in the last weeks of gestation, nonetheless demand great prudence in the interpretation of data obtained by this new means. The incidence of various motor patterns was assessed in a group of 10 preterms at low risk for neurological damage by means of weekly video recordings. The preliminary results seem to indicate that many items in the motor repertoire do not change substantially at the approach to 40 weeks conceptional age and are similar to those described in the fetus.

Child Development↗
PubMedDate not supplied

Genetics of sex determination: exceptions that prove the rule.

The dogma that male and female embryos develop in identical fashion until SRY initiates Sertoli cell differentiation in the hitherto bipotential gonad is in need of reevaluation in the light of data that do not fit into this scheme. One of the exceptions that proves the rule of sex determination is true hermaphroditism, the existence of individuals with both testicular and ovarian tissue. Furthermore, the two types of tissues are asymmetrically distributed, ovaries being more common on the left side and testes and ovotestes on the right. Hermaphrodite mice also exhibit bilateral asymmetry of gonad differentiation, but in the opposite direction: ovaries on the right, testes and ovotestes on the left. To explain these asymmetries, it is necessary to consider the relationship between growth and gonadal differentiation. The idea that accelerated growth precedes histological differentiation of the testis has recently been confirmed by the finding that Sry induces cell proliferation in fetal mouse gonads, suggesting that the differentiation of Sertoli cells may be dependent on a critical cell number. Recent evidence has also shown that XY embryos develop faster than their XX counterparts at very early stages of development, and it has been reported that SRY and ZFY are expressed in early human and murine embryos. The relationship between growth and sex differentiation links the mammalian system with those of nonmammalian vertebrates with temperature-dependent sex determination. Early growth differences between male and female human embryos question the belief that all sex differences in later life are due to gonadal hormones.

Animals↗
PubMed2000

Nidogen-1. Expression and ultrastructural localization during the onset of mesoderm formation in the early mouse embryo.

Nidogen-1, a key component of basement membranes, is considered to function as a link between laminin and collagen Type IV networks and is expressed by mesenchymal cells during embryonic and fetal development. It is not clear which cells produce nidogen-1 in early developmental stages when no mesenchyme is present. We therefore localized nidogen-1 and its corresponding mRNA at the light and electron microscopic level in Day 7 mouse embryos during the onset of mesoderm formation by in situ hybridization, light microscopic immunostaining, and immunogold histochemistry. Nidogen-1 mRNA was found not only in the cells of the ectoderm-derived mesoderm but also in the cytoplasm of the endoderm and ectoderm, indicating that all three germ layers express it. Nidogen-1 was localized only in fully developed basement membranes of the ectoderm and was not seen in the developing endodermal basement membrane or in membranes disrupted during mesoderm formation. In contrast, laminin-1 and collagen Type IV were present in all basement membrane types at this developmental stage. The results indicate that, in the early embryo, nidogen-1 may be expressed by epithelial and mesenchymal cells, that both cell types contribute to embryonic basement membrane formation, and that nidogen-1 might serve to stabilize basement membranes in vivo. (J Histochem Cytochem 48:229-237, 2000)

Animals↗
PubMed1991

Embryonic and fetal hemopoiesis: an overview.

Our current knowledge of embryonic and fetal hemopoiesis is critically reviewed in this article. In both murine and human systems, embryonic and fetal development is associated with multiple switching in the sites of hemopoiesis. The phenomenon is first extraembryonic, occurring in blood islands of the yolk sac. Hemopoietic stem cells (HSC) appear to derive from hemangioblasts that are of mesodermal origin. Yolk sac milieu is permissive only for erythropoiesis which proceeds synchronously and may be erythropoietin-insensitive. Yolk sac milieu is not permissive for the development of other cell lines. The final product is nucleated red cells. Yolk sac hemopoiesis is an example par excellence of primitive (as compared to definitive) form of hemopoiesis. HSC then seem to migrate via the bloodstream to the liver and spleen to seed these tissues, which then carry the burden of hemopoiesis until birth and for some time thereafter. Here also erythropoiesis predominates, but some granulopoiesis also occurs. Thus, the milieu is not totally impermissive. Hemopoiesis is in definitive form, lacking synchronicity of cell growth with the end product being anucleated cells and synthesized hemoglobin not limited to embryonic type. The site of hemopoiesis is finally transferred to the bone marrow, which is predominantly granulopoietic. Certain cellular and embryological features of these types of hemopoiesis in the context of more recent molecular understanding of stem cell homing are discussed.

Animals↗
PubMedDate not supplied

Complications in the transition from fetal to neonatal life.

The transition from fetus to neonate is a time of significant physiologic adaptation. In addition to the normal physiologic tasks of transition, some neonates must also cope with underlying congenital abnormalities, birth injury, or disease. Careful assessment and astute nursing care are needed during the period of transition to ensure that the neonate who is experiencing problems with transition is recognized and appropriate interventions are initiated. This article examines the physiology of transition and discusses factors placing the neonate at risk of illness. A plan of care for neonates experiencing symptoms of underlying disease during transition is presented.

Adaptation, Physiological↗
PubMed1995

[Evaluation of newborn maturation and gestational age using the Ballard-Klimka scale].

Results of prospective studies of 1404 consecutive vaginal and cesarean deliveries of newborns weighted > or = 2500 g were analyzed in relation to their maturity. It was stated that Ballard Maturation Score is a valid accurate assessment tool for precise interpretation of the degree of fetal maturity, but not of the calendar length of gestation, especially beyond 36 weeks. Therefore it was reasonable to propose a constant distribution of scores: 39 +/- 3 points within the period from 37% to 43% weeks while at the 28th week: 10 +/- 2 points (Ballard-Klimek scale of pregnancy dating) instead of therefore used J. L. Ballard rule that only newborns at 44 weeks can have scores of 50 and infants with shorter gestational age have lower values, e.g. 33 at the 37th week.

Body Weight↗
PubMed2001

Sry promoters from domesticus (Tirano) and C57BL/6 mice function similarly in embryos and adult animals.

Introduction of the Y chromosome from a Mus musculus domesticus (Tirano) subspecies into the Mus musculus musculus C57BL/6 (B6) inbred strain background results in sex reversal in XY offspring. It has been hypothesized that the domesticus testis-determining Y (Tdy) locus is misregulated in B6 genome, thereby impairing sex determination in B6.Y(Dom) animals. The identification of a gene in the sex-determining region on the Y chromosome (Sry) as the Tdy has provided a means to experimentally examine this hypothesis. We have generated several lines of B6 transgenic mice harboring a green fluorescent protein gene directed by a Sry promoter from the domesticus (Tirano) Y chromosome. Detailed analysis of the transgene expression was conducted in both fetal and adult tissues of the transgenic mice. The domesticus Sry promoter was capable of directing the expression of the green fluorescent protein gene in a pattern similar, if not identical, to that of the endogenous B6 Sry gene. These observations suggest that the domesticus Sry promoter is not involved in the postulated misregulation of the domesticus (Tirano) Sry gene in the B6 genomic background. These results are discussed with reference to a second hypothesis invoking incompatible protein interaction(s) as a mechanism of aberrant sex determination in B6.Y(Dom) animals.

Animals↗
PubMed1996

Metabolism and cell allocation during parthenogenetic preimplantation mouse development.

Diploid parthenogenetic postimplantation mouse embryos, containing two maternal genomes, are characterized by poor development of extraembryonic membranes derived from the trophectoderm and primitive endoderm of the blastocyst. This is thought to be caused by a deficiency of expression of paternally derived imprinted genes. Here we have compared the inner cell mass, from which the primitive endoderm and fetal lineages are derived, and the trophectoderm, which forms a major component of the placenta, in parthenogenetic and fertilized preimplantation embryos. We have also studied the metabolism from the 1-cell to the blastocyst stage. Cell numbers were reduced in the ICM and TE of parthenogenetic blastocysts compared to fertilized blastocysts. This was thought to be due to the increased levels of cell death observed in these lineages. Pyruvate and glucose uptake by parthenogenetic embryos was similar to that by fertilized embryos throughout preimplantation development. However, at the expanded blastocyst stage glucose uptake by parthenogenetic embryos was significantly higher than by fertilized embryos. The implications of the actions of imprinted genes and of X-inactivation is discussed.

Animals↗
PubMed1992

ACTH-like peptides in postimplantation mouse embryos: a possible role in myoblast proliferation and muscle histogenesis.

ACTH and related peptides are mitogens for certain mesodermal cell types such as adrenocortical cells, T-lymphocytes, and skeletal myoblasts. In order to postulate a possible physiological role for these peptides in skeletal muscle histogenesis, it is necessary to establish whether they are present in muscle forming anlagens of postimplantation mouse embryos. By radioimmunoassay and immunofluorescence with antibodies specific for ACTH, we have detected these peptides in many areas of mouse embryos including neural tube, limb buds, eye lens, and myotomal muscles. During fetal development, immunoreactivity decreased in muscle tissue and appeared in visceral ganglia. Furthermore, primary myotubes or C2C12 myotubes, but not muscle or 3T3 fibroblasts, release significant levels of ACTH immunoreactive peptides into the culture medium. Using a microassay for mitogen production, primary myotubes or C2C12 myotubes, but not other mesodermal cells (with the exception of dermal fibroblasts) were shown to release factors into the medium which support myoblast proliferation. Neutralizing antibodies against ACTH inhibit myoblast but not fibroblast proliferation in a dose-dependent fashion. Based on these results, we propose that myotube-derived mitogens (including ACTH-like peptides) promote the proliferation of surrounding myoblast during muscle histogenesis in vivo.

Adrenocorticotropic Hormone↗
PubMed1989

Biopsy of preimplantation mouse embryos: development of micromanipulated embryos and proliferation of single blastomeres in vitro.

We have developed a technique to sample the preimplantation embryo, which may, in the future, be applied to prenatal diagnosis of genetic disease. Using micromanipulation, we aspirated a single blastomere from 4-cell mouse embryos. This procedure had no effect on in vitro development; 98% of control and 94% of biopsied embryos reached the blastocyst stage after 48 h in culture. Furthermore, after transfer to pseudopregnant recipient mice, the rate of fetal development of biopsied embryos was not significantly different from control embryos, although implantation rate was significantly reduced (mean +/- SD: biopsied 53.1 +/- 4.0, control 81.8 +/- 8.4, p less than 0.001). For the first time we have produced monolayer cell cultures derived from single preimplantation blastomeres. Individual biopsied blastomeres were cultured in vitro on different extracellular matrix components. Significantly greater cell proliferation was obtained in wells coated with fibronectin (FN), laminin (LN), and a complex of laminin and nidogen (LNC) than in a less specific matrix of swine skin gelatin (SSG). Mean (+/- SE) cell nuclei number per well after 6 days in culture was 6.4 +/- 2.1, 11.9 +/- 1.5, 19.8 +/- 2.9, and 20.9 +/- 2.6 in wells coated with SSG, LN, FN, and LNC respectively.

Animals↗
PubMed1994

Developmental arrest of fertilized eggs from the B6.YDOM sex-reversed female mouse.

When the Y chromosome of a Mus musculus domesticus mouse strain is placed onto the C57BL/6J (B6) inbred background, the XY progeny develop ovaries or ovotestes but never normal testes during fetal life. While some of the hermaphroditic males become fertile, none of the XY females produces litters. Here, we examined the fertility and development of oocytes derived from the XY female mouse. With or without preceding injection of gonadotropins, female mice were mated with normal B6 males, and their embryos were recovered at various developmental stages. In vitro fertilization was performed with the eggs recovered from the oviduct after treatment with gonadotropins. Development of embryos was examined by both light and electron microscopy. The results indicate that the oocytes released from the B6.YDOM ovary were efficiently fertilized and often initiated the first cell cleavage, but all embryos died during early preimplantation periods. Even when oocytes were fertilized in vitro, minimizing their exposure to the XY oviduct/uterus environment, most embryos died at the 1- or 2-cell stage. A few exceptional embryos reached the 4- or 8-cell stage, but abnormalities were evident in both nuclear and cytoplasmic structures of all embryos. After cleavage, neighbouring blastomeres were only loosely associated, and microvilli were abundant at the intercellular interfaces. We postulate that oocytes of the B6.YDOM female mouse become defective during XY ovarian differentiation, and, hence, fail to proceed through normal embryonic development.

Animals↗
PubMed1991

[Effect on school performance of prenatal exposure to the Hiroshima atomic bomb].

As a part of the continuing assessment of the effects on the developing embryonic and fetal brain of exposure to ionizing radiation, the school performance of prenatally exposed survivors of the atomic bombing of Hiroshima and a suitable comparison group have been studied. In this report, the changes in performance in seven school subjects according to dose are compared under the dosimetry system (DS86) instituted in 1986 at the Radiation Effects Research Foundation. The sample involves 929 children whose fetal absorbed dose are known and includes 14 severely mentally retarded persons. The findings can be summarized as follows: 1) Damage to the 8-15 week fetal brain appears to be linearly related to the absorbed dose, as judged by the simple regression of average school-performance score on dose. Damage to the fetus exposed at 16-25 weeks after fertilization appears similar to that seen in the 8-15 week group. Canonical and multiple correlations also show a highly significant relationship of exposure 8-15 weeks and 16-25 weeks after fertilization to achievement in school. This trend is stronger, however, in the earliest years of schooling. 2) In the group exposed within 0-7 weeks following fertilization, or 26 or more weeks after fertilization, there was no evidence of a radiation-related effect on scholastic performance. 3) These results parallel those previously found in prenatally exposed survivors with respect to achievement in standard intelligence tests in childhood and development of severe mental retardation.

Age Factors↗
PubMed2001

Time course of female-to-male sex reversal in 38,XX fetal and postnatal pigs.

In an attempt to understand the etiology of intersexuality in pigs, we thoroughly analyzed the gonads of 38,XX (SRY negative) female to male sex-reversed animals at different developmental stages: during fetal life [50 and 70 days postcoitum (dpc)], just after birth [35 days postpartum (dpp)] and during adulthood. For each animal studied, we performed parallel histological and ultrastructural analyses on one gonad and RT-PCR analysis on the other gonad in order to define the expression profiles of sexually regulated genes: SOX9, 3beta-HSD, P450 aromatase, AMH, FOXL2, and Wnt4. Light and electron microscopic examination showed that testicular cords differentiated in XX sex-reversed gonads but were hypoplastic. Although the testicular cords contained gonia at the fetal stages, the germ cells had all died through apoptosis within a few weeks after birth. Ultrastructurally normal Leydig cells also differentiated, but later, and enclosed whorl-like residual bodies. At the fetal stages, three of the six genes studied in the intersex gonads presented, as early as 50 dpc, a modified expression profile corresponding to an elevated expression of SOX9 and the beginning of AMH and P450 aromatase gene transcription. In addition to genes involved in the testicular pathway, the same gonads expressed FOXL2, an ovarian-specific factor. The ovaries of true hermaphrodites were ineffective in ensuring correct folliculogenesis and presented abnormal expression profiles of ovarian specific genes after birth. These results indicate that the genes involved in this pathology act very early during gonadogenesis and affect the ovary-differentiating pathway with variable expressivity from ovarian germ cell depletion through to trans-differentiation into testicular structures.

Animals↗
PubMedDate not supplied

Ultrasonic mensuration of fetal limb bones in the second and third trimesters.

Growth of fetal limb bones has been examined in a prospective cross-sectional study in 530 patients between 13 and 42 weeks of gestation by ultrasound. The length of the femur, tibia, humerus, and radius were measured in all cases, and fibula and ulna in 393 cases. For each week of gestation mean lengths (+/- 2 standard deviations) were calculated. All limb bones showed linear growth from 13 weeks to 25 weeks of gestation, after which the growth curve appeared nonlinear. A strong linear relationship (r greater than 0.98) between the BPD and bone length was found for each bone. In five aborted fetuses, prenatal sonographic measurements of the ossified diaphyses were compared with the postnatal radiologic measurement (30 limb bones). A good agreement was found (difference between ultrasound and X-ray measurements 0.7 +/- 0.5 [SD] mm or 3.0 +/- 2.4 [SD]%), indicating that ultrasound images the ossified diaphysis.

Anthropometry↗
PubMed1994

Effects of insulin on in vitro bone formation in fetal rat parietal bone.

We examined the effects of insulin on bone formation including the mineralizing process. Twenty-day fetal rat parietal bones were cultured for 96 h on grids in a serum-free medium. For the precise assessment of bone formation, histomorphometry, with an image analyzing system, was used to measure the areas of mineralized bone and bone matrix, and the numbers of osteoblasts and osteoclasts. In order to confirm the effects of insulin on bone mineralization, the calcium content of the bone and the release of previously incorporated 45Ca into the medium were measured. Insulin, at a concentration of 10(-6) M or higher, increased the areas of mineralized bone and bone matrix, and the number of osteoblasts. Osteoclasts were seldom observed in bones on day 0 or in bones treated with insulin. In bones treated with insulin at a concentration of 10(-6) M, the calcium content of bone increased. At an insulin concentration of 10(-7) M or higher, the dry weight of decalcified bone increased. Lactate production in the medium increased dose-dependently. The inhibited release of 45Ca in bones indicated that insulin acts by increasing calcium retention. We demonstrated that insulin has an effect on bone-forming and bone-resorbing cells to enhance the bone forming process from matrix formation to mineralization.

Animals↗
PubMed2001

Extraordinary case of matrotrophy in the African skink Eumecia anchietae.

The viviparous African skink, Eumecia anchietae, exhibits a matrotrophic fetal nutritional pattern. Until well after the limb bud stage, extravitelline nutritional provision is in the form of holocrine secretion originating from the stratified uterine epithelium of the uterine incubation chambers. Uterine secretions are absorbed by a specialized yolk sac ectoderm and chorioallantois through histotrophy. The yolk sac is not in close contact with the uterine lining from the limb bud stage onwards. The yolk sac ectoderm forms invaginations filled with uterine secretion and consists of a single layer of vacuolated hypertrophied cells bearing microvilli. The chorioallantois at the limb bud stage is extensive, well-vascularized, and not intimately associated with the uterine epithelium. Where the uterus is folded, the chorioallantois may interdigitate loosely. Chorionic cells are low to high columnar, clearly vacuolated, and bear microvilli. The allantoic layer consists primarily of squamous cells exhibiting villous projections. By the time embryos have well-defined digits, the specialized yolk sac ectoderm has regressed and the yolk sac lumen has been invaded by vitelline cells. The chorioallantois is very extensive and in areas greatly folded. Where it contacts the uterine epithelium, a proper chorioallantoic placenta is formed. Cell layers of the chorioallantois and uterine epithelium are thin and cuboidal to squamous in appearance. The chorioallantoic placenta is simple in structure, occurs throughout the incubation chamber, and is epitheliochorial in arrangement. It is unknown whether the placentome observed in other highly matrotrophic scincids is formed in late stage embryos of this species.

Africa↗