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PubMed1995

Pattern of keratinocyte growth factor and keratinocyte growth factor receptor expression during mouse fetal development suggests a role in mediating morphogenetic mesenchymal-epithelial interactions.

Mesenchymal cells are required for the induction of epithelial development during mammalian organogenesis. Keratinocyte growth factor (KGF) is a mesenchymally derived mitogen with specific activity for epithelial cells, suggesting that it may play a role in mediating these interactions. To further evaluate this hypothesis, in situ hybridization was used to examine the spatial distribution of KGF and KGF receptor (KGFR) transcripts during organogenesis and limb formation in mouse embryos (days 14.5 through 16.5). To facilitate this aim, mouse KGF cDNA clones were isolated. There was extensive identity between the deduced mouse KGF protein sequence and that of its human and rat cognates, indicating that this gene has been highly conserved during mammalian evolution. In addition, mouse KGF protein was purified from fibroblasts and demonstrated to be structurally and functionally similar to human KGF protein. For organs within the integumental, respiratory, gastrointestinal, and urogenital systems, whose development is dependent upon mesenchymal-epithelial interactions, KGF mRNA was detected in mesenchymal cells, while epithelial cells expressed transcripts for the KGFR, KGF and KGFR mRNA was also expressed in certain other tissues such as perichondrium, cartilage of developing bones, developing skeletal muscle, and visceral smooth muscle whose development is not regulated by mesenchymal-epithelial interactions. KGF expression was also detected in tissues isolated from human embryos, suggesting similar functions for KGF in human development. Taken together, our results suggest that KGF plays an important role in mediating mesenchymal-epithelial interactions during organogenesis, but may also have other developmental functions in tissues not governed by such interactions.

Adult↗

PubMed1993

[The homeo box--a genetic key to fetal development].

A fundamental question in medicine and biology is how does a fertilized oocyte develop into an adult organism. By combining classical genetics, experimental embryology and gene technology it is now possible to analyze how the complicated process of embryogenesis is regulated by genes. One important genetic element in this regard is the homeobox, which was initially discovered in the genes controlling the early development of the fruit fly Drosophila melanogaster. The homeobox is also present in the genomes of vertebrates, and this discovery has shed new light upon the mechanisms which establish the formation of cell patterns in complex species, such as humans.

Animals↗

PubMed1999

Anthropological measurements of the skeleton and parathyroid glands growth during fetal development.

The article presents the investigation of histomorphological differentiation and growth of parathyroid glands in human fetus from the second to the ninth lunar month. The longer and the shorter diameter of these glands were measured. The obtained values are compared with the development and the growth intensity of the skeleton (biparietal head diameter and femoral length of a fetus from lunar months 3 to 9) and with the role of the placenta in the mentioned processes. The results of our investigation show the concordance of the skeletal growth with the development and histomorphological differentiation of these glands. The factors involved in these processes point out the complex relationship between the mother and fetus during osteogenesis, expressed on the hormonal level, in mineral metabolism and placental activity.

Anthropometry↗

PubMed1993

DNA methylation of the fragile X locus in somatic and germ cells during fetal development: relevance to the fragile X syndrome and X inactivation.

To obtain insights into mechanisms responsible for methylation of CpG islands on the inactive X chromosome of normal females, we examined methylation of the fragile X (FraX) locus in a variety of tissues from normal fetuses and adults, and from males with the FraX syndrome. We identified 20 CCGG sites (MspI-HpaII sites M1-M20) within a 12-kb BglII fragment that includes the CpG island. Sites M3-M18, within the 1.2-kb CpG island are unmethylated on the active X in normal males and females at all ages and in all tissues studied. In contrast, these sites are at least partially methylated on the inactive X chromosome in a variety of tissues from normal females by six weeks from conception. The exceptional tissues are chorionic villi and gonads, which are significantly undermethylated. In addition, fetal germ cells are unmethylated at site M3, which is methylated on the inactive X in other tissues; thus, the methylation imprint of the inactive X has been erased. Methylation of the locus on the fragile X chromosome is similar to that of the normal inactive X but is more extensive and less heterogeneous. This suggests that the expansion of the island and the greater number of CpGs that result from amplification of the CGG repeat enhance the methylatibility of the island. Additional studies show that the chromatin of the CpG island is nuclease hypersensitive on the active X but insensitive on both inactive and FraX.

Adult↗

PubMed1998

Antibody repertoire development in fetal and neonatal piglets. I. Four VH genes account for 80 percent of VH usage during 84 days of fetal life.

VDJ rearrangement and VH gene usage during fetal development in 35 outbred piglets was examined by PCR amplification of VDJs; VDJs were subsequently characterized by hybridization with VH-specific gene probes and by sequencing. VDJ rearrangement was first seen in the fetal liver on day 30 of a 114-day gestation. Four VH genes (V(H)A, V(H)B, V(H)C, and V(H)E) accounted for approximately 80% of all VH gene usage regardless of gestational age, choice of piglet, or lymphoid tissue tested; D(H)A and D(H)B were used in >90% of the fetal VDJs examined. Evidence of somatic hypermutation during fetal development was not found. The proportion of the four prominent fetal VH genes did not differ significantly between cDNA and DNA, suggesting the absence of selective B cell differentiation. A comparison of recombination signal sequences, flanking sequences, and framework sequences of these fetal genes with other germline VH genes of swine offered no clue as to their selective usage. N-region additions were prominent on day 40 but not on day 30, suggesting that the onset of terminal deoxynucleotidyltransferase activity occurs after 30 days of fetal development. These collective findings indicate that the preimmune, "natural Ab" repertoire of the fetal piglet is largely restricted to the use of four nonpolymorphic and nonmutated VH genes and two nonmutated DH segments. This suggests that the preimmune repertoire of swine is either highly restricted or almost entirely determined by junctional diversity in complementarity-determining region-3.

Animals↗

PubMed2005

Leptin and Ob-Rb receptor isoform in the human digestive tract during fetal development.

CONTEXT: Leptin, partially produced by the stomach, is a hormone involved in energy balance and regulation of food intake. It also regulates some digestive functions through its functional receptor Ob-Rb expressed by gastrointestinal epithelial cells. OBJECTIVE: The objective of the study was to investigate the temporal and spatial appearance of Ob-Rb in the human digestive tract and leptin in the stomach. DESIGN: The esophagus, stomach, and intestine samples of 7- to 24-wk-old human fetuses and adult mucosae were studied by RT-PCR, immunohistochemistry, and Western blot. Leptin was measured by RIA in amniotic fluids at 16-33 wk gestation. RESULTS: All mucosae expressed Ob-Rb (mRNA and/or protein) between 7 and 9 wk gestation. Leptin protein appeared by 8 wk in the gastric mucosa, whereas leptin mRNA was detected around 11 wk. Leptin levels in amniotic fluids were significantly higher during the second than during the third trimester. Overall, Ob-Rb immunoreactivity was higher in young fetuses, during the period corresponding to the formation of gastric buds and primitive intestinal crypts and the beginning of differentiation of epithelial cell types, than in the oldest. Leptin added to culture medium of gastrointestinal explants from 10- to 12-wk-old fetuses appeared to affect DNA synthesis as compared with controls, indicating that leptin receptor functionality was developing. CONCLUSIONS: The strong expression of leptin, in amniotic fluid when fetuses begin swallowing then in the gastric mucosa, and the early presence of Ob-Rb in mucosae suggest a possible role for leptin, exerted endoluminally and in a paracrine pathway, in the developmental process (growth and/or maturation) of the human digestive tract.

Amniotic Fluid↗

PubMed2002

Matrix metalloproteinase-21, the human orthologue for XMMP, is expressed during fetal development and in cancer.

We have characterized a novel human matrix metalloproteinase (MMP-21) from human placenta DNA complementary to RNA (cDNA). The 569 amino acid translation of the cDNA includes all the typical features of an MMP family member, namely a signal sequence, a prodomain with a PRCGVPD motif, a zinc-binding catalytic domain with an HEIGHVLGL sequence, and a hemopexin-like domain flanked by two cysteine residues. Furthermore, MMP-21 has a furin activation sequence, but no transmembrane sequence nor a cytoplasmic domain. As in Xenopus laevis and Cynops pyrrhogaster there is an additional insertion of approximately 30 amino acids between the prodomain and the catalytic domain, which is poorly conserved between the species and is in human MMP-21 especially proline rich. The MMP-21 gene has seven exons and is located in chromosome 10. This new MMP is the human orthologue for XMMP and CyMMP expressed during gastrulation of X. laevis and C. pyrrhogaster, respectively. A 2.5 kb messenger RNA was observed in fetal liver by Northern analysis. By reverse transcription-polymerase chain reaction, MMP-21 is expressed in various human fetal and adult tissues as well as in cancer cell lines. MMP-21 protein can also be detected in malignancies such as ovarian and colon carcinomas by immunohistochemical staining. Our findings suggest that MMP-21 functions in embryogenesis and tumor progression.

Amino Acid Sequence↗

PubMed2003

[Differentiation of human pancreatic endocrine cells in the period of fetal development].

The stereological analysis of electron micrographs of pancreatic endocrine cells (A and B) obtained from human fetuses at gestational months 4 to 7 was performed to assess the volume densities of membranous organelles (mitochondria, rough endoplasmic reticulum, Golgi complex), polysomes and secretory granules. The differences were established in the ratios of the volume densities of organelles and secretory granules in the process of differentiation. The morphometric characteristics of total A- and B-cell populations as well as the quantitative data on the structural organization of endocrine cells at various stages of differentiation are presented.

Cell Differentiation↗

PubMed2006

Ca2+ regulation in detrusor smooth muscle from developing fetal sheep bladders.

Sheep fetus is a useful model to study in utero bladder outflow obstruction but little is known about cell physiology of fetal bladders. To remedy this defect we have characterised intracellular Ca(2+) regulation in fetal sheep myocytes of different developmental ages. Fetal detrusor myocytes had a similar resting [Ca(2+)](i) to adult cells and exhibited transient [Ca(2+)](i) increases in response to carbachol, ATP, high-K, caffeine and low-Na. The carbachol transients were abolished by atropine and caffeine; the ATP response was blocked by alpha,beta-methylene ATP; high-K-evoked [Ca(2+)](i) rises were antagonised by verapamil. The maximal responses to carbachol, high-K, caffeine and low-Na in fetal cells were similar to those of adult counterparts, whilst the ATP response was smaller (p < 0.05). These variables were largely similar between the three gestational groups with the exception of ATP-induced response between early fetal and adult bladders (p < 0.05). Dose-response curves to carbachol demonstrated an increase of potency between mid-gestation and early adulthood (p < 0.05). These data show that muscarinic receptors coupled to intracellular Ca(2+) release, P2X receptor-linked Ca(2+) entry, depolarisation-induced Ca(2+) rise via L-type Ca(2+) channels, Na(+)/Ca(2+) exchange and functional intracellular Ca(2+) stores are all operational in fetal bladder myocytes. Whilst most of Ca(2+) regulators are substantially developed and occur at an early fetal age, a further functional maturation for cholinergic sensitivity and purinergic efficacy continues throughout to adulthood.

Adenosine Triphosphate↗

PubMed1996

Localization of large-T oncoprotein during the embryonic and fetal development of transgenic mice.

Oncoproteins are not only involved in the development of tumors but also play a role in physiological regulation in embryonic growth and differentiation. The mechanisms by which regulation is accomplished in embryonic stages differ from postnatal or adult stages. Oncoproteins responsible for tumors in the adult, i.e., products of proto-oncogenes, are prevented from causing tumors in the embryo. If oncogenes are introduced artificially into the embryo. will they be governed by the embryonic regulation described above? To answer this question we used transgenic mice in which the hybrid construct MSV-SV40-Large-T, composed of the Simian-Virus-Oncogene. Large-T with its SV40-promotor and the Moloney Murine Sarcoma Virus (MSV)-enhancer, had been integrated. Under the influence of large-T expression, these animals develop either brain or endocrine pancreas tumors. In the present investigation, we localised large-T expression during development of mouse embryos and fetuses. Interestingly, we saw large-T positive reactions in organ anlagen other than those that later develop tumors. We found large-T antigens in cartilage anlagen, e.g., in ribs and vertebrae, particularly in fetuses of days 14 to 17, and also in a variety of epithelial cells such as in the lung or the choroid plexus. Our results indicate that, as for proto-oncogene products, the effect of an artificially introduced transgenic oncogene product can also be regulated by embryonic cells.

Animals↗

PubMed1989

[Mg++-ATPase activity in circumventricular capillaries during fetal development of rats].

We performed an ultracytochemical study of Mg++-ATPase as a marker of maturation in circumventricular capillaries at the developmental stage of rats, from 19 gestational days to 18 postnatal day, comparing with hippocampal capillaries. During the course of perinatal development, the predominant site of the Mg++-ATPase activity in circumventricular capillaries was shifted from the luminal cell membrane to the antiluminal cell membrane and the total enzyme activity was markedly increased. In all hippocampal capillaries observed, the predominant site of the Mg++-ATPase activity was the antiluminal cell membrane. It was suggested that immaturity of circumventricular capillaries may be one of the causative factors leading to intraventricular and subependymal hemorrhages in neonates.

Animals↗

PubMedDate not supplied

Epidemiological studies on disturbances of human fetal development in areas with various doses of natural background radiation. II. Relationship between incidences of hydatidiform mole, malignant hydatidiform mole, and chorionepithelioma and gonad dose equivalent rate of natural background radiation.

The relationships between gonad dose equivalent rates and incidences of chorionic disease (i.e., hydatidiform mole, malignant hydatidiform mole, and chorionepithelioma) were analyzed with Kendall's rank correlation and regression methods. Data used were from 11 prefectures of Japan with various dose rates of natural background ionizing radiation between the years 1974 to 1976. The results suggested an association of the incidence of chorionic disease with the radiation dose rate in the very low dose-rate range.

Adult↗

PubMedDate not supplied

Cocaine effects on fetal development: a comparison of clinical and animal research findings.

The clinical and animal literature describing the effects of cocaine use during pregnancy is reviewed. The difficulties associated with studying populations using illicit drugs during pregnancy and the multiple risk factors present in cocaine-using pregnant women limit the strength of the drug-associated effects. Nevertheless, cocaine use during pregnancy is associated with a significant number of obstetrical complications, small for gestational age infants and neurobehavioral abnormalities. In animal studies, only the neurobehavioral abnormalities could be demonstrated following the administration of non-toxic doses of cocaine. Furthermore, animal studies indicate that neurochemical changes, including those identified in the neuroendocrine axis, persist into adulthood.

Abnormalities, Drug-Induced↗

PubMed2001

Galectin-1 and galectin-3 in fetal development of bovine respiratory and digestive tracts. Comparison of cell type-specific expression profiles and subcellular localization.

Histochemical monitoring of developmental processes is presently centered on protein-protein interactions. However, oligosaccharides have the potential to store and transmit biological information. Carbohydrate chains of cellular glycoconjugates present determinants for binding of endogenous lectins. This interaction can be relevant for developmental processes. In fact, beta-galactosides and their derivatives serve as ligands for members of the lectin family of galectins. Since it is unclear to what extent functions of different galectins differ or overlap, hereby introducing redundancy into this system, monitoring of galectin presence during tissue maturation should include more than one type of galectin (galectin fingerprinting). Here, we focus on the two most frequently described ones, namely the homodimeric prototype galectin-1 and the chimera-type galectin-3, the latter one so far not characterized from bovine tissue. In the first step, we have detected its presence biochemically in addition to the abundant galectin-1 in bovine respiratory and digestive tracts during development. Evidently, diversification of the primitive foregut will not lead to an alteration of this property. Immunohistochemistry revealed clear differences in the galectins' localization profiles. Galectin-1 expression is strong in mesenchymal cells, especially smooth muscle cells, while epithelial lining harbors galectin-3. A gradual increase in staining intensity with development is especially observed in the case of galectin-3. Notably, this change is accompanied by a shift from primarily nuclear localization to the cytoplasm, an alteration not seen for galectin-1. However, nuclear presence of galectin-1 is encountered. Thus, the delineation of differences in expression of galectin-1 and -3 with respect to cell types and in the developmental course of subcellular localization argues in favor of mediation of nonoverlapping functions by these two homologous, endogenous lectins.

Animals↗

PubMed1993

Association of ultrarapid freezing of mouse oocytes with increased polyploidy at the pronucleate stage, reduced cell numbers in blastocysts and impaired fetal development.

Mature mouse oocytes were frozen ultrarapidly with a cryoprotectant solution consisting of 3.5 mol dimethylsulfoxide l-1 and 0.5 mol sucrose l-1 or exposed to the freezing solution and recovered. Freshly collected oocytes were used as controls. After ultrarapid freezing and thawing, a high mean percentage of oocytes (78%) survived. The incidence of parthenogenetic activation in frozen-thawed oocytes was not increased. After insemination in vitro, the rate of two-cell formation was decreased (59% versus 69%). Examination of the chromosome complement of first-cleavage embryos revealed that the incidence of polyploid embryos was four times that of the control group (23% versus 6%). Fewer fertilized eggs progressed to the blastocyst stage (49% versus 81%) and the mean number of cells per blastocyst was decreased. Furthermore, the capacity of transferred blastocysts to develop in vivo was reduced. Autopsy at day 17 of gestation revealed that the proportion of embryos implanting was lower in the embryos derived from ultrarapidly frozen-thawed oocytes. Furthermore, some of the living fetuses were abnormal, but our sample size is too small for the effect to be significant. In the solution control group, no differences were found compared with the control group. Although the study needs further results to draw definite conclusions, our findings question whether the applied protocol is suitable for mouse oocytes.

Animals↗

PubMed1998

Neonatal head circumference and related indices of disturbed fetal development in schizophrenic patients.

Neonatal head circumference and dermatoglyphic patterns were examined in 60 schizophrenic patients with previous findings of elevated rates of minor physical anomalies. Neonatal head circumference was reduced in patients vs neonatal matched-controls. Patients did not differ from healthy adult controls on total finger ridge count, a-b palmar ridge count, or pattern type asymmetry. No significant relationships were found in patients between neonatal head circumference, dermatoglyphics and minor physical anomalies, with one exception: reduced a-b palmar ridge count was associated with abnormalities of the mouth. No relationship was found between patients' neonatal head circumference and their adult head circumference. Adult male schizophrenic patients had larger head circumference relative to body length than their male controls.

Adult↗

PubMed1997

Embryonic and fetal development in different genotypes in pigs.

It is widely accepted that uterine capacity, not ovulation rate, is the greatest restraint on litter size in pigs. Recently, the reproductive strategy(s) of the Chinese Meishan pig, a breed which farrows three to five more piglets per litter than US or European pig breeds, has come under intense scrutiny. It was initially determined that the Meishan female could farrow more viable piglets per litter than US or European pig breeds, with a uterine size and ovulation rate equivalent to those of less prolific breeds. It has become apparent that the Meishan conceptus exhibits a reduced trophectoderm mitotic rate during the preimplantation period, elongates from fewer cells and remains smaller throughout gestation compared with conceptuses from less prolific US or European pig breeds. This strategy by the Meishan conceptus for a lower growth rate results in a marked reduction in conceptus loss through day 18 of gestation compared with less prolific breeds. An additional strategy is required in the Meishan to allow the larger number of viable fetuses to survive after day 30 of gestation when uterine capacity becomes limiting. Our research has demonstrated that the rapid growth of the fetus in US pig breeds appears to require continued placental growth to increase the surface area for nutrient exchange. In contrast, the increased number of smaller Meishan fetuses achieve the same increase in placental efficiency by markedly increasing the density of placental blood vessels at the fetal-maternal interface. This proliferation of placental blood vessels obviates the need for marked increase in placental size.

Animals↗

PubMed1996

Expression of neurofibromatosis 2 transcript and gene product during mouse fetal development.

Neurofibromatosis 2 (NF2) is an autosomal dominant inherited disorder that predisposes to benign tumors of the nervous system as well as a variety of ocular abnormalities. In contrast to NF1, NF2 is associated with only minor developmental abnormalities. The human NF2 gene encodes a tumor suppressor protein, termed schwannomin or merlin, which is a member of a superfamily of proteins thought to link cytoskeletal elements to cell membrane components. To determine the pattern of NF2 gene expression in mouse embryos, we sequenced the mouse NF2 gene and used in situ hybridization and antischwannomin antibodies to determine the developmental expression of the NF2 gene. Schwannomin was detected in most differentiated tissues but was undetectable in undifferentiated tissues. In particular, schwannomin was not detectable in mitotic neuroepithelial cells, the perichondrium, the liver, the neocortex, and the ventricular zone of the developing cerebral cortex. In the heart, expression was observed in all developmental stages beginning on embryonic day 8. In the eye, which shows developmental abnormalities in NF2 patients, expression was detected in the cells of the lens and in the pigment epithelium but weakly detected in retinal neurons. The most striking example of tightly regulated NF2 expression was observed in cells migrating from the ventricular zone to the cortical plate on embryonic days 15 and 16. Only cells in the intermediate zone expressed schwannomin, indicating that schwannomin may play an important role in cellular migration.

Amino Acid Sequence↗