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PubMed1993

Fetal development in the rat following disruption of maternal renal function during pregnancy.

Pregnant Sprague-Dawley rats received subcutaneous injections of mercuric chloride (1-4 mg/kg) on either gestation day 7, 9, 11, or 13 to determine effects of altered maternal renal function on embryonic and fetal development. Maternal renal function, assessed by urinalysis, was markedly disrupted for at least 48 hours after treatment and resulted in decreased maternal body weight gain. Residual effects on maternal kidney weight were evident on GD 21 when the females were killed and the fetuses removed and examined for visceral and skeletal development. We did not observe an increased incidence of malformations in the offspring for exposure on any day of gestation. Maternal exposure to mercuric chloride slightly impaired fetal growth over several gestational exposures periods and changed the pattern of rib formation when exposure occurred early in organogenesis. The extent of the changes could not, however, be related to the immediate degree or duration of altered maternal renal function. Rather, we found correlations between lasting effects of exposure as measured by maternal renal weight on GD 21 and super-numerary lumbar rib induction on GD 7 and 9; while for the relationship with fetal weight, the strongest correlation with maternal kidney weight occurred following exposure on GD 9 (P < 0.01), with weaker correlations (P < 0.10) for GD 7 and 13 exposures. Maternal serum urea was negatively correlated with fetal weight from the GD 7 exposure. This study supports the concept that some specific forms of maternal toxicity may be associated with limited manifestations of developmental toxicity, but, in general, embryonic development was observed to proceed normally in the presence of marked disruptions in maternal renal physiology. Maternal toxicity, especially as routinely measured in developmental toxicity studies, cannot be looked upon as a single disease. Instead, each manifestation must be examined for what it signifies to the physiology and well being of the female and for cause-and-effect relationships with fetal observations. Maternal toxicity and developmental toxicity should not be etiologically linked solely because of their concurrent appearance on the dose-response curve.

Acute Kidney Injury↗
PubMed1994

Development of the tendon of Todaro during the human embryonic and fetal periods.

This study covers the development of Todaro's tendon during human embryonic and fetal periods. The tendon primordium first appears when human embryos attain a CR length of 22 mm, but it only becomes well-defined at 24 mm CR length. The tissue that will form the tendon proceeds exclusively from the inferior endocardial cushion. The tendon establishes a close relationship with the base of the septum secundum during its path towards the right venous valve, carrying myocardial tissue out and forming the fasciculus limbicus inferior to muscular tissue. The tendon's relationship with the superior aspect of the atrioventricular node primordium during the first part of its path is of particular interest. The relationship is most intriguing when the node morphology is least defined. This would explain the possible embryogenesis of extra atrioventricular nodes. We also consider Todaro's tendon to be largely responsible for the development of the sinus band which protrudes as a crest inside the right atrium. This band is particularly well-developed in the fetal heart and provides an explanation for the large sub-Eustachian sinus cavity.

Embryonic and Fetal Development↗
PubMed1996

Identification of five embryonic hemoglobins of rat and ontogeny of their constituent globins during fetal development.

Hemoglobins of rats switch from an embryonic to an adult type during fetal development. However, very little is known about the structures and molecular species of hemoglobins occurring in the fetal life of rats. In the present study we isolated five embryonic hemoglobins, designated E1, E2, E3, E4, and E5, from the blood of rat fetuses on day 14 of gestation by ion exchange chromatography. Reverse-phase high performance liquid chromatography revealed that these hemoglobins each consist of two kinds of globins: E1(11 alpha:epsilon 1), E2(1 alpha: epsilon 1), E3(zetta: epsilon 1), E4(1 alpha: epsilon 3), and E5(zetta: epsilon 3), respectively. The complete amino acid sequences of the zetta, epsilon 1, and epsilon 3 globins were determined. The zetta globin showed characteristic features common in alpha-type embryonic globins of known species in that the N-terminus is blocked and the amino acid at position 38 is Gln. epsilon 1 and epsilon 3 are beta-type embryonic globins, sharing 73.7% amino acid homology. Interestingly, they are more similar to the corresponding mouse beta-type embryonic globins, y and z, respectively, than to each other, implying that these globins have evolved orthologously from common ancestral proteins. It was also shown that the zetta, epsilon 1, and epsilon 3 globins are almost completely replaced by the adult type alpha and beta globins in the blood of rat fetuses by day 18 of gestation.

Amino Acid Sequence↗
PubMed1989

Process elimination underlies ontogenetic change in the distribution of callosal projection neurons in the postcentral gyrus of the fetal rhesus monkey.

During fetal development, the regional distribution of callosal projection neurons in the rhesus monkey's postcentral gyrus changes from a uniform to a discontinuous pattern. To determine if this developmental change reflects the retraction of transient callosal projections, two different fluorescent tracers were injected into the brain of fetal monkeys of known gestational ages. Fast blue was injected into the entire postcentral gyrus of one hemisphere, whereas a second tracer (rhodamine latex beads or diamidino yellow) was injected into the caudal portion of the postcentral gyrus of the other hemisphere. The rostral portion of the postcentral gyrus (contralateral to the hemisphere injected with fast blue) was subsequently examined for the presence of labeled cells. In animals injected early in fetal development, on embryonic day 110 or younger and sacrificed 4 weeks later, there were numerous cells labeled with both tracers. In contrast, very few double-labeled cells were found in fetuses injected at an older age, embryonic day 135. We interpret these findings as showing that early in fetal development, when callosal projection neurons in the postcentral gyrus show a continuous distribution pattern, single cells in the rostral portion of this gyrus possess at least two collaterals, one projecting to the contralateral hemisphere and the other to the caudal portion of the gyrus. Subsequently, many of these neurons retract callosal collaterals while maintaining ipsilateral projections. Thus, process elimination accounts for the establishment of the discontinuous distribution of callosal neurons found in the postcentral gyrus of the mature primate.

Animals↗
PubMed1992

Adverse effects of gonadotrophin treatment on pre- and postimplantation development in mice.

The effect of gonadotrophins on pre- and postimplantation development in mice was investigated by superovulating C57BL/6J/Bom females with pregnant mares' serum gonadotrophin (PMSG) and human chorionic gonadotrophin (hCG) or by inducing ovulation with hCG. In both hormone treated groups, the proportion of abnormal preimplantation embryos increased compared with naturally ovulating animals. Postimplantation mortality increased and the mean number of live fetuses per pregnant mouse decreased in superovulated and hCG-treated mice compared with controls. Embryonic growth was highly retarded. Mean weight of live fetuses in superovulated and hCG-treated mice was reduced and skeletal examination revealed developmental retardation. In conclusion, superovulation as well as induction of ovulation adversely affected embryonic and fetal development.

Animals↗
PubMed1990

Epidermal growth factor and transferrin receptor expression in human embryonic and fetal epidermal cells.

Epidermal growth factor receptors (EGFR) and transferrin receptors (TFR) are known to be involved in cell proliferation and to be expressed in normal human epidermis. To date little is known about EGFR and TRF expression in human skin during embryonic and fetal development. In the present work, we studied skin specimens from 30 aborted embryos and fetuses ranging from 7 to 31 weeks estimated gestational age. Monoclonal antibodies to EGFR and TFR were applied on frozen skin sections using an amplification biotin-streptavidin-fluorescein technique. TFR was faintly expressed on epidermal basal cells throughout embryonic and fetal development, as it is in adult epidermis. Up to week 12, EGFR was uniformly expressed on cells of the basal, intermediate and periderm cell layers. From the midfetal period onwards, the suprabasal cell layers showed a decreased staining compared with the basal layer. During the third trimester the cornified cell layer was completely negative. The hair germ and heir peg cells were positive. Later, the outer root sheath and hair bulb remained labelled, with less staining of the hair cone. The sebaceous and eccrine sweat glands were also labelled. These results suggest that in embryonic and fetal epidermis, TFR expression is not correlated with cellular proliferation, whereas EGFR appear to be associated with proliferating and undifferentiated cells.

Adult↗
PubMed2003

Do unliganded thyroid hormone receptors have physiological functions?

Thyroid hormone (TH) is required for the development of vertebrates and exerts numerous homeostatic functions in adults. TH acts through nuclear receptors which control the transcription of target genes. Unliganded and liganded thyroid hormone receptors (TRs) have been shown to exert opposite effects on the transcription of target genes in vitro. However, the occurance of an aporeceptor activity in vivo and its potential physiological significance has not been clearly addressed. Several data generated using experimental hypothyroidism and thyrotoxicosis in wild type and TR knockout mice support the notion that apoTRs have an intrinsic activity in several tIssues. ApoTRs, and in particular TRalpha1, are predominant during the early stages of vertebrate development and must be turned into holoTRs for post-natal development to proceed normally. However, the absence of striking alterations of embryonic and fetal development in mice devoid of TRs indicates that apoTRs do not play a fundamental role. During development, as well as in adults, apoTRs rather appears as a system which increases the range of transcriptional responses to moderate variations of T3.

Aging↗
PubMed1998

Expression of nerve growth factor and its high-affinity receptor Trk-A in the rat pancreas during embryonic and fetal life.

The expression of functional receptors for nerve growth factor in insulin-producing cell lines grown in vitro has recently been demonstrated. The possible importance of signals transduced via these receptors in the control of islet maturation has been proposed based on data obtained using an in vitro culture system. To further support this hypothesis, we have studied the expression of Trk-A, the high-affinity receptor for NGF, in vivo during the embryonic and fetal development of the rat pancreas. We have also examined the expression of NGF during the same period. Immunohistological analysis shows that at embryonic day 11 (E11), Trk-A is expressed by the epithelial cells of the presumptive pancreas. The few pancreatic endocrine cells present at that stage express Trk-A. At E12 and E16, Trk-A expression was detected in the developing ductal network. The endocrine cells located in the ducts express Trk-A while those that have migrated into the surrounding mesenchyme now stain negative for Trk-A. By E20, Trk-A expression by ductal cells has considerably decreased and can be detected only in small ducts closely associated with islet-like structures. These islet-like structures stain negative for Trk-A. After birth, insulin-positive cells arranged into islets re-express Trk-A. During the same period, NGF mRNA is found to be expressed in the developing pancreas. The expression of Trk-A and its ligand NGF in the pancreas during embryonic and fetal life suggests that NGF and its receptor could play an important role in the development of the pancreas.

Animals↗
PubMed1982

An immunologic hypotheses concerning some congenital diseases and malformations.

Congenital diseases such as hyaline membrane disease perhaps may come about by transplacental passage of high titred IgG anti HLA antibodies to a fetal pulmonary tissue. Conceivably transplacental passage of high titred anti HLA antibodies (or as yet unidentified antibodies) may interfere with development of tissues at any stage of embryonic and fetal development where the HLA antigen (or other antigen) are present.

Antibodies↗
PubMed1996

Flow cytometric sorting of sperm: influence on fertilization and embryo/fetal development in the rabbit.

Viable, intact rabbit sperm, prepared, processed, and flow cytometrically sorted, were used in this study to determine the influence of flow sorting on fertilization and embryo development. In experiment I, flow-sorted or control (unstained and unsorted) sperm were surgically inseminated into the uterine horn of hormonally primed does (10 to 12 does per time point). At 42 hr postsurgical insemination, flushed embryos were assessed for development. Fetal development was determined at day 7, day 14, and day 21 post-surgical insemination. Embryos resulting from does surgically inseminated with control sperm at 42 hr post-insemination were observed to be at the early morula stage of development (> 16 cell), whereas embryos from does inseminated with flow sorted sperm were at the 8- to 16-cell stage. No difference was observed between treatments at day 7, 14, or 21, however, there was a significant decrease in fetus number per doe inseminated with flow-sorted sperm over time. In experiment II, mature oocytes were flushed from the oviducts of superovulated does and coincubated in vitro (IVF) with flow-sorted or control rabbit sperm. Oocytes observed at 6 hr post-coincubation exhibited swollen sperm heads in the cytoplasm, demonstrating that fertilization had occurred (2 PN + T). There was a higher percentage of fertilized oocytes by 8 hr post-coincubation for both control (31%) and flow-sorted sperm (31%) when used for IVF. By 10 and 12 hr post-coincubation, little difference was observed in the number of fertilized oocytes between sperm treatments (52% and 66% for control vs. 57 and 54% for flow-sorted, respectively). These studies demonstrate that flow-sorted sperm are capable of fertilizing mature oocytes under in vitro conditions. In addition they show that flow sorting may not negatively influence fertilization events, but likely interferes during early embryonic and fetal development.

Animals↗
PubMed1993

The human gene encoding cytokeratin 20 and its expression during fetal development and in gastrointestinal carcinomas.

The differentiation of the predominant cell types of the mucosal epithelium of the mammalian gastrointestinal tract is characterized by increasing amounts of an intermediate-sized filament (IF) protein designated cytokeratin (CK) 20 which is a major cellular protein of mature enterocytes and goblet cells. Here we report the isolation of the human gene encoding CK 20, its complete nucleotide sequence and the amino acid sequence deduced therefrom that identifies this polypeptide (mol. wt. 48553) as a member of the type I-CK subfamily. Remarkable, however, is the comparably great sequence divergence of CK 20 from all other known type I-CKs, with only 58% identical amino acids in the conserved alpha-helical 'rod' domain of CK 20 and, e.g. CK 14. Using riboprobes corresponding to exon 6 of the gene in Northern blot and ribonuclease protection assays, we show that the approximately 1.75 kb mRNA encoding CK 20 is specifically produced in cells of the intestinal and gastric mucosa, including tumors and cell lines derived therefrom. The appearance of CK 20-positive cells in human embryonic and fetal development and in adult tissues has been studied using immunohistochemistry with CK 20-specific antibodies. CK 20 synthesis has first been recognized at embryonic week 8 in individual 'converted' simple epithelial cells of the developing intestinal mucosa. In later fetal stages, CK 20 synthesis extends over most goblet cells and a variable number of villus enterocytes. The distribution of CK 20-positive cells in the developing gastric and intestinal mucosa is similar to--but not identical with--the pattern in the adult intestine in which all enterocytes and goblet cells as well as certain 'low-differentiated' columnar cells contain CK 20, whereas the neuroendocrine ('enterochromaffin') and Paneth cells are negative. In gastrointestinal carcinomas similarly examined, CK 20 has been detected in almost all cases (50/52) of colorectal adenocarcinomas, including all grades of differentiation and malignancy and also metastatic tumors, whereas CK 20 immunostaining in gastric carcinomas has been found less consistent and more heterogeneous. The possible biological meaning of the specific expression of the CK 20 gene in certain cells of the gastrointestinal tract and carcinomas derived therefrom and the regulatory mechanisms involved in the integration of the protein in the IF cytoskeleton are discussed.

Adenocarcinoma↗
PubMed1991

Variabilities in prenatal development of orofacial system.

Reliable information on embryonic and fetal development of the human oro-facial system is meager. Much of the data available at present is not entirely reliable, because it was derived from a small number of specimens. An embryological approach with human materials is important for establishing a normal standard of development including individual variabilities as well as clarifying the embryogenesis and etiology of defective development (Nishimura et al. 1977). It is important in human craniofacial embryology to know the variabilities, that is, individual differences in developmental phenomena of the oro-facial region during human prenatal life. In recent times the importance of morphologic investigations of human development has received less emphasis. Yet, without thorough knowledge of the basic facts of prenatal human development, erroneous assumptions can be made in more dynamic approaches and lead investigators astray. Knowledge of prenatal development of human orofacial structures and some of their deviations will therefore be welcomed by many basic scientists and clinicians in the field of facial clefts and other craniofacial malformations. The author was engaged in the collection and systematic study of human embryos and fetuses with Dr. Hideo Nishimura, Emeritus Professor of Kyoto University, Kyoto, Japan, and has been studying the normal and abnormal development during prenatal life. Several results obtained from the study of a large number of specimens are presented laying stress on the orofacial development.

Cleft Lip↗
PubMed1984

[Fetal development].

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Embryonic and Fetal Development↗
PubMed1994

Effects of persistent chlorinated hydrocarbons on fertility and embryonic development in the rabbit.

The commercial polychlorinated biphenyl (PCB) formulation Aroclor 1260 (4 mg/kg body weight), technical grade dichlorodiphenyltrichloroethane (DDT; 3 mg) and Lindane (gamma-hexachlorocyclohexane; 0.8 mg) were administered orally, either separately or in combination, to sexually mature female rabbits three times per week for 12-15 weeks. Oviductal and uterine luminal fluid, cleavage stage embryos (day 1 post coitum), blastocysts (day 6), fetuses, exocoelic fluid and placentae (day 11) were analysed, firstly for chlorinated hydrocarbon residues, and secondly for embryonic and fetal development. The doses applied were well tolerated by the treated animals. PCB and DDT accumulated in uterine secretions (day 6) but not in oviductal luminal fluid (day 1). Both chlorinated hydrocarbons were found in preimplantation blastocysts. Residues in day 11 fetuses were 16- (DDT) or 18-fold (PCB) higher than in day 6 blastocysts. Significant amounts were also detected in placental tissue and in exocoelic fluid. A specific accumulation of the highly chlorinated biphenyl congener no. 180 was noted in fetuses, placentae and exocoelic fluid. The clear accumulation of the chlorinated hydrocarbon compounds in luminal fluid and embryonic tissue is contrasted by rather weak effects on fertility. No statistically significant differences between treated animals and controls were observed for fertilization rate and pre- and post-implantation (up to day 11 post coitum) losses. However, in females exposed to PCB, a 20% higher loss of blastocysts was noticed, as compared with controls (P > 0.05). This effect was shown on day 6 of embryonic development and may be due to the embryotoxic activities of PCB.

Animals↗