bluuebunny/crossref_metadata_2025 huggingface dataset:
Promotion of differentiation of newt primary spermatocytes into spermatids by mammalian FSH via Sertoli cells
Authors: Ji Zai‐Si , Kubokawa Kaoru , Abé Shin‐Ichi
Published: June 2005

Our previous studies showed that mammalian follicle‐stimulating hormone (FSH) promoted the differentiation of primary spermatocytes into elongated spermatids in organ culture of testes fragments from Cynops pyrrhogaster. To elucidate the mechanism of FSH action, in this study the testes in the primary spermatocyte stage were dissociated and fractionated into germ and somatic cells, the latter comprising more than 80% Sertoli cells. Radioreceptor assays showed that FSH bound to somatic cells, very probably Sertoli cells, but not to germ cells. FSH elevated intracellular cyclic AMP levels in somatic but not germ cells.

In cultures of cell aggregates somatic cells stimulated the differentiation of primary spermatocytes into round spermatids even in the absence of FSH, but to a greater extent in the presence of FSH. However, in the absence of somatic cells the extent of differentiation was similar, irrespective of the presence of FSH. Luteinizing hormone (LH) had no stimulatory effects. Most, if not all, of the somatic cells adherent to germ cells were Sertoli cells based on the criterion that they contained lipid droplets. This indicates that FSH stimulates the differentiation of primary spermatocytes via Sertoli cells.

To examine if direct contact between Sertoli cells and germ cells is required for the promotion of differentiation, Sertoli and germ cells were cultured in two different compartments which were separated by a permeable membrane. Under these conditions Sertoli cells did not promote the differentiation of primary spermatocytes either in the absence or presence of FSH, indicating that direct contact between germ and Sertoli cells is required for Sertoli cells to promote the differentiation of primary spermatocytes. © 1995 Wiley‐Liss, Inc.
Successful production of chimeric honeybee larvae
Authors: Omholt Stig W. , Rishovd Svein , Hagen Arne , Elmholdt Odd , Dalsgard Brita , Fromm Sigurd
Published: June 2005

The honeybee (Apis mellifera) is likely to become the major model system for resolving the genetic basis of advanced perceptual and behavioural abilities of highly social insects because of the high level of knowledge regarding its physiology and social behaviour and its ease of handling. Here we report for the first time genetic transformation of honeybees by the production of chimeric larvae obtained by nuclear transplantation, identified by use of a genetic marker. Two chimeras expressed only the genotype of the donor indicating developmental totipotency of nuclei up to the 11th cleavage mitosis. © 1995 Wiley‐Liss, Inc.
Ontogeny of respiratory function in crustaceans exhibiting either direct or indirect development
Authors: Spicer John I.
Published: June 2005

Dialysed haemolymph from the planktonic larvae of the Norwegian lobster Nephrops norvegicus possessed a lower O2 affinity than the benthic adult stage at equivalent pH. This difference could be correlated with the ability to maintain O2 uptake during progressive hypoxia; adult individuals showed better developed regulation than the larvae. The intrinsic O2 affinity of both larval and adult haemocyanin (Hc) could be modified by preexposure to chronic hypoxia. In contrast, there were no significant differences noted in either Hc O2 affinity or the ability to regulate O2 uptake during progressive hypoxia between newly hatched and adult individuals of the direct developing amphipod Echinogammarus pirloti. Unlike the case in N. norvegicus preexposure to chronic hypoxia did not result in any change in respiratory performance at the level of the whole animal or in intrinsic Hc O2 affinity. The changes (or absence of them) in these aspects of the respiratory biology of the two species examined are discussed in the context of their ecological requirements. © 1995 Wiley‐Liss, Inc.
Changes in the distribution of fibroblast growth factor in the teleostean testis during spermatogenesis
Authors: Watanabe Akihiko , Onitake Kazuo
Published: June 2005

The distribution of fibroblast growth factor (FGF) in the testes of Salvelinus leucomaenis and Oryzias latipes was investigated by immunofluorescence staining. In S. leucomaenis, spermatogonia were strongly stained in the infantile testis. When human chorionic gonadotrophin (HCG) was injected into individual fish, the uptake of 5‐bromo 2′‐deoxyuridine (BrdU) occurred within a day. At the same time, FGF became undetectable in spermatogonia, but appeared for the first time around the testicular somatic cells. A similar distribution was seen in the mature testes of S. leucomaenis and O. latipes. The positively immunostained area corresponded to the predominant site of the Sertoli cells. This pattern of distribution of FGF suggests that FGF plays an important role in the initiation and progression of spermatogenesis in the teleostean testis. © 1995 Wiley‐Liss, Inc.
Salt loading stimulates secretion by the lingual salt glands in unrestrained Crocodylus porosus
Authors: Taylor Greg C. , Franklin Craig E. , Grigg Gordon C.
Published: June 2005

In previous studies, the lingual salt glands of crocodiles have failed to secrete in response to a salt load. This is unlike salt glands in other reptiles and in birds, and it has led to some doubt about the extent to which the salt glands in crocodiles are of functional importance.

Believing that the failure to secrete may be associated with the artificial restraint associated with measurement, or with the removal of study animals from the water, we designed and built an electronic sensor which would monitor secretions from the salt glands of crocodiles while they were in water and undisturbed.

Under these conditions, the salt glands were observed to secrete spontaneously. Under salt loading, delivered via a femoral vein cannula, there was a rapid production of secretion from the glands. Secretion was stimulated by methacholine and acetylcholine chlorides also. The results support the view that the lingual salt glands in crocodilians are stimulated by a salt load and that previous attempts to demonstrate this may have been influenced by the experimental conditions. © 1995 Wiley‐Liss, Inc.
Inhibitory action of hypoxanthine on meiotic resumption of denuded pig follicular oocytes in vitro
Authors: Miyano Takashi , Ebihara Misa , Goto Yuri , Hirao Yuji , Nagai Takashi , Kato Seishiro
Published: June 2005

The present study was conducted to investigate the direct action of hypoxanthine, which has been reported to be present in pig follicular fluid, on spontaneous meiotic resumption of pig denuded oocytes in vitro. No oocytes, which were surrounded by a cumulus and some membrana granulosa cells directly adjacent to it from healthy antral follicles, underwent germinal vesicle breakdown (GVBD) when they were cultured in serum‐supplemented 199 with or without 4 mM hypoxanthine. On the other hand, 81% of denuded oocytes prepared from such cumulus‐oocyte‐granulosa cell complexes showed GVBD after 24 h of culture. Hypoxanthine inhibited significantly this spontaneous resumption of meiosis in denuded oocytes. The inhibitory action of hypoxanthine was dose dependent at concentrations of 1–6 mM and was reversible following subsequent culture of the oocytes in hypoxanthine‐free medium. However, premature chromosome condensation was observed in oocytes cultured in hypoxanthine‐supplemented medium, and the oocytes released from the influence of hypoxanthine completed GVBD and reached the second metaphase slightly faster than those freshly isolated from the follicle. These results suggest that hypoxanthine inhibits spontaneous meiotic resumption of pig oocytes in vitro. However, the inhibitory action of hypoxanthine does not prevent all events involved in GVBD from occurring. © 1995 Wiley‐Liss, Inc.
Calcium oscillations and calcium waves coordinate rhythmic contractile activity within the stellate cell layer of medaka fish embryos
Authors: Simon Joanne Z. , Cooper Mark S.
Published: June 2005

During gastrulation and body axis formation in medaka (Oryzias latipes) fish embryos, rhythmic contraction waves sweep across a tissue sheet known as the periderm, which covers both the developing embryo and its associated yolk cell. Cope et al. ([1990] J. Exp. Zool., 254:270–275) have found that these contractions are generated by a layer of stellate‐shaped cells which is closely apposed to the inner surface of the periderm. In this paper, we show that rhythmic contractions in the stellate cell layer are correlated with elevations of intracellular [Ca2+]. Medaka periderms were first explanted and secured to microscope coverslips using a modified plasma clot culture technique. The explants were then loaded with the calcium indicator dye Fluo‐3AM and observed with time‐lapse epifluorescence confocal microscopy. Rises of intracellular [Ca2+] were observed to propagate from cell to cell in the stellate cell layer, in the form of intercellular waves. After a latency of a few seconds, a coordinated contraction within the stellate cell layer ensued. Rhythmic Ca spikes were also observed within individual stellate cells. In many cases, rises of intracellular [Ca2+] preceded cellular contraction in these individual cells by several seconds. The Ca oscillations and Ca waves that occur in medaka stellate cells represent one of the earliest expressions of Ca‐based excitability and contractility within the blastoderm of post‐fertilization vertebrate embryos. © 1995 Wiley‐Liss, Inc.
Allozymic and cytological evidence for hemiclonal, all‐paternal, and mosaic offspring of the hybridogenetic stick insect Bacillus rossius‐grandii grandii
Authors: Tinti Fausto , Scali Valerio
Published: June 2005

Bacillus hybridogens represent the first example of hemiclonal reproduction among invertebrates and they were analyzed in the present study for comparison with vertebrate hybridogenetic complexes (Poeciliopsis and Rana). Experimental crosses of southeastern hybridogenetic B. rossius‐grandii grandii females with both the parental species and hybrid males were carried out to test the reproductive potential of hybridogens. Allozyme and chromosome markers indicated that hemiclonal females actually reproduced in a variety of ways. Hybridogenesis was the most common and the rossius unassorted haploset was passed to the progeny while the grandii haploset was discarded during meiosis and replaced by that of the fathering male. Andro‐genesis, which was much rarer, led to the production of two types of all‐paternal offspring: unipa‐rental progeny of both sexes and all‐male progeny with the same allozyme and chromosome structure as their father. Mosaics of two kinds were also produced: the “h + h” type, with two different hybridogenetic cell lines; and the “h + a” type, with one hybridogenetic and one androgenetic cell line. Mosaics evolved into intersexes when their cell lines were sexually discordant. Among the evolutionary outcomes of this wide array of reproductive ways seems to be a shift from hemiclonality to clonality. This possibility is supported by the well‐established parthenogen B. whitei and the occasional production of rare invariant specimens from the northwestern hybridogenetic form B. rossius‐grandii benazzii. Bacillus and other unisexuals provide evidence of numerous reproductive interactions between hybrids and their bisexual relatives: the occurrence of such interactions may play an important role in the persistence, diversification and evolution of unisexuals. © 1995 Wiley‐Liss, Inc.
Effect of hypothyroidism induced by propylthiouracil and thiourea on male and female reproductive systems of neonatal mice
Authors: Chan W. Y. , Ng T. B.
Published: June 2005

The effect of hypothyroidism induced by 6‐propyl‐2‐thiouracil (PTU) or thiourea (TU) on the development of the reproductive system in male and female neonatal ICR mice was investigated. PTU or TU was injected subcutaneously into experimental animals from postnatal day 1 (PD1) onward. The histological changes of the reproductive organs, formation of ovarian follicles, and spermatogenesis were examined on PD 14, 21, and 28, and the fertility of the hypothyroid mice in adulthood was followed. It was found that PTU or TU treatment did not produce an effect on the histology of the neonatal uterus and oviduct. In contrast, the drugs induced a decrease in the number of primordial follicles, multilaminar follicles, and Graafian follicles in the ovary. The number of follicles with degenerated follicular cells was increased. In the testis both PTU and TU treatments brought about a decrease in the number of seminiferous tubules with developing spermatids although the mean diameter of seminiferous tubules and the histology of the testis, epididymis, seminal vesicle, and coagulating gland was unaffected. The mating between hypothyroid females and euthyroid males and that between hypothyroid males and euthyroid females were normal with regard to the pregnancy rate, litter size, and sex ratio of offspring. The somatic growth of the resulting offspring was normal. It is concluded that the retarding effect on ovarian and testicular development in mice during neonatal period was not serious enough to adversely affect reproduction in the hypothyroid animals. © 1995 Wiley‐Liss, Inc.
Mirror‐image duplication of the primary axis and heart in Xenopus embryos by the overexpression of Msx‐1 gene
Authors: Chen Yiping , Solursh Michael
Published: June 2005

The Msx‐1 gene (formerly known as Hox‐7) is a member of a discrete subclass of homeobox‐containing genes. Examination of the expression pattern of Msx‐1 in murine and avian embryos suggests that this gene may be involved in the regionalization of the medio‐lateral axis during earlier development. We have examined the possible functions of Xenopus Msx‐1 during early Xenopus embryonic development by overexpression of the Msx‐1 gene. Overexpression of Msx‐1 causes a left‐right mirror‐image duplication of primary axial structures, including notochord, neural tube, somites, suckers, and foregut. The embryonic developing heart is also mirrorimage duplicated, including looping directions and polarity. These results indicate that Msx‐1 may be involved in the mesoderm formation as well as left‐right patterning in the early Xenopus embryonic development. © 1995 Wiley‐Liss, Inc.
Cytogenetic studies on diploid and triploid oogenesis in interspecific hybrid fish between Oryzias latipes and O. curvinotus
Authors: Kurita Jun , Oshiro Takashi , Takashima Fumio , Sakaizumi Mitsuru
Published: June 2005

Interspecific hybrid females produced from reciprocal crosses between Oryzias latipes and O. curvinotus show reduced fertility, but they do lay eggs. When fertilized by sperm from one of the parental species, such eggs developed into triploid males and females. To confirm the ploidy of the eggs spawned by the hybrid females we examined the karyotypes of backcross and gynogenetic offspring. The karyotype of the China‐West Korean medaka, O. latipes sinensis, was 2n, with 46 chromosomes, including a pair of “large” metacentrics, whereas O. curvinotus had 2n, 48, without such a chromosome pair. F1 hybrids had a karyotype 2n, 47, with one large chromosome. When the hybrid females were backcrossed to O.l. sinensis, the offspring had a karyotype of 3n, 70, with two large chromosomes. By contrast, when backcrossed to O. curvinotus, the progeny of the hybrid females had a karyotype of 3n, 71, with one large chromosome. After gynogenetic treatment with UV‐irradiated sperm of rainbow trout, the eggs spawned by the hybrid females developed into diploid (2n, 47) fish with one large metacentric chromosome. These results indicate that the hybrid females spawn unreduced diploid eggs with one complete chromosome set for both parental species. A triploid female, in contrast to the diploid hybrid females, spawned eggs with reduced chromosome number, giving rise to hyperdiploid embryos when fertilized by sperm. Transplantation of scales and electrophoretic analysis of proteins indicated that a hybrid female and her gynogenetic offspring can be regarded as “clones” with identical sets of chromosomes. © 1995 Wiley‐Liss, Inc.
Physiology of atympanate tibial organs in forelegs and midlegs of the cave‐living Ensifera, Troglophilus neglectus (Raphidophoridae, Gryllacridoidea)
Authors: Cokl Andrej , Kalmring Klaus , Rössler Wolfgang
Published: June 2005

The complex tibial organs of the Ensiferan species Troglophilus neglectus (Raphidophoridae, Gryllacridoidea) do not differ significantly in their morphology in all six legs. They consist of a normal developed subgenual organ and an intermediate organ (when compared with the conditions in tettigoniids). Physiologically, the receptor cells of the complex tibial organs of the fore‐ and midlegs could be grouped into 11 functional types. Four of these types belong probably to the intermediate organ; the cells of these types respond to frequencies from 700 Hz to 2,000 Hz to both substrate‐ and airborne sound but are more sensitive to the former. The remaining seven types belong to the subgenual organ. Their receptors are tuned to stimuli within frequencies ranging from 200 Hz to 700 Hz. The classification into different functional types and their attribution to the two receptor organs were derived from a comparison with the physiological properties of the receptors of the complex tibial organs in the midlegs of tettigoniids. In the Troglophilinae the subgenual and intermediate organs are structurally very similar to those of the midleg receptor organs of tettigoniids; only the most distal part of the intermediate organ and the crista acoustica is missing. Consistent with the similarities in the proximal part of the receptor complex, the receptor cells of the subgenual and intermediate organs show similar physiological characteristics. © 1995 Wiley‐Liss, Inc.
Heat flow is measurable from Artemia franciscana embryos under anoxia
Authors: Hand Steven C.
Published: June 2005

A recent report has concluded that heat flow under anoxia from encysted embryos of the brine shrimp Artemia is unmeasurable (Hontoria et al. [1993] J. Exp. Biol., 178:149–159). This observation contrasts with two earlier communications that have reported low but measurable energy flow from these gastrulae (Hand and Gnaiger [1988] Science, 239:1425–1427; Hand [1990] J. Comp. Physiol. [B], 160:357–363). In order to re‐examine this issue, up to 20 g wet mass of embryos was loaded per experiment into sealed ampoules (25‐ to 50‐fold more tissue than in previous studies) and calorimetric analyses were conducted. Even after 50–60 h, a clearly measurable heat dissipation was recorded from these anoxic embryos (0.0128 ± 0.0007 mW·g dry mass−1; ± 1 SE, n =6). The results confirm the presence of measurable heat flow under anoxia. The rate of heat dissipation measured in this study is at the limit of detection for the instrument used by Hontoria et al. ([1993] J. Exp. Biol., 178:149–159). A second important issue is whether any of the low heat flow under anoxia is associated with processes involving ATP turnover, a point that is evaluated in this study but that remains unresolved. However, calculations suggest that macromolecular degradation may explain a significant portion of the anoxic heat flow. © 1995 Wiley‐Liss, Inc.
Sound production in Pituophis melanoleucus (Serpentes: Colubridae) with the first description of a vocal cord in snakes
Authors: Young Bruce A. , Sheft Stan , Yost William
Published: June 2005

The pine, gopher, or bull snake (Pituophis melanoleucus) makes two different defensive sounds. Hisses are characterized by lack of frequency and amplitude modulation; bellows have a brief initial period of high‐amplitude, broad‐frequency sound followed by a longer period of lower‐amplitude, constant‐frequency sound. Both defensive sounds contain distinct harmonic elements. The modulation and harmonic nature of these sounds seems to be unique among snakes. The larynx of Pituophis is unusual in having an epiglottal keel, a dorsal expansion of the cricoid cartilage, previously proposed to contribute to sound production; however, this study shows that it plays only a small role in increasing the amplitude of bellows. Within the larynx of Pituophis is a “vocal cord,” the laryngeal septum, which is a flexible, horizontal shelf of tissue that divides the anterior portion of the larynx. Removal of the laryngeal septum alters the defensive sounds and eliminates their harmonic elements. The laryngeal septum is unique among previously described vertebrate vocal cords or folds because it is supported by the cricoid (as opposed to arytenoid) cartilage and is a single (as opposed to bilaterally paired) structure. © 1995 Wiley‐Liss, Inc.
Tensegrity model of pattern formation during cytokinesis of a ciliate, Paramecium: Effects of an inhibitor of phosphorylation, 6‐dimethylaminopurine, and of adenine
Authors: Kaczanowska J. , Iftode F. , Jeanmaire‐Wolf R. , Clérot J.‐C. , Kiersnowska M. , Adoutte A.
Published: June 2005

During cytokinesis of the ciliate Paramecium, the two oral apparatuses (OAs), localized close to the fission line, are displaced to a mid‐region of daughter cells by a tearing off of the OAs and adjacent cortices from the fission line and their subsequent movement toward the poles of the dividing cell. Two possible mechanisms for this displacement were examined: 1) a mechanism whereby the contraction of the fission line in the vicinity of OAs brings about the change of configuration of the adjacent cortices and subsequent displacement of OAs and 2) a mechanism whereby programmed transient depolymerization of the inner cytoskeletal contractile infraciliary lattice in the vicinity of OAs acts as a motive force for displacement of the OAs, together with the most superficial outer lattice of the cytoskeleton which does not disassemble. Our working hypotheses were based on observations on the behavior of the outer lattice, where the infraciliary lattice disintegrates and the fission line assembles.

To study the mechanics of pattern formation during cytokinesis of Paramecium, morphogenesis was followed in the presence of an inhibitor of phosphorylation, 6‐dimethylaminopurine (6‐DMAP), and of adenine, which prevented disassembly of the inner lattice and arrested cytokinesis and dislocation of OAs. Nearly all defects in morphogenesis were correlated with failure of the infraciliary lattice to disassemble and failure of the fission line to assemble. It appears that the superficial cortical structures and the contractile infraciliary lattice represent a tensegrity model of morphogenesis during cytokinesis in Paramecium. © 1995 Wiley‐Liss, Inc.
Neural gene therapy for inherited diseases with mental retardation: Principles and prospects
Authors: Schuchman Edward H. , Ioannou Yiannis A. , Rattazzi Mario C. , Desnick Robert J.
Published: June 2005

Gene therapy for inborn errors of metabolism that cause mental retardation remains a major challenge to gene therapists. In general, such disorders can be divided into two categories: those in which the primary site of pathology resides outside of the central nervous system (CNS), leading to the accumulation of toxic compounds that cross the blood‐brain barrier and cause neurologic dysfunction, and those in which the primary site of pathology resides within the neurons of the CNS. We focus on the strategies and prospects for treating the latter group of diseases, which require delivery of therapeutic genes or gene products to the CNS. Both ex vivo and in vivo approaches can be used. Among the ex vivo strategies, transplanted, genetically corrected hematopoietic stem cells obtained from a patient can enter the CNS and establish microglia within the brain that then secrete therapeutic proteins. Alternatively, neural cells such as oligodendrocytes or astrocytes can be obtained by brain biopsy, genetically corrected in the laboratory using viral or nonviral vectors, then autologously transplanted back into patients for migration and secretion of the therapeutic gene products. Among the in vivo delivery techniques, direct stereotaxic injection of therapeutic gene constructs can be used to correct a metabolic abnormality in a specific region. Intracarotid injection of therapeutic genes coupled with transient disruption of the blood brain barrier could also be used to obtain global delivery. Various approaches to the treatment of inborn errors of metabolism with mental retardation can be envisioned. We discuss each of the major gene delivery systems and related therapeutic strategies. © 1995 Wiley‐Liss, Inc.
Phenylketonuria: A model for hepatic gene therapy
Authors: Fang Bingliang , Eisensmith Randy C. , Woo Savio L. C.
Published: June 2005

Classical phenylketonuria (PKU; Mckusick MIM Cat 261600) is an autosomal recessive disorder caused by a deficiency of hepatic phenylalanine hydroxylase (phenylalanine 4‐monooxygenase; PAH; EC 1.14.16.1). The hyperphenylalinemia and mental retardation typical of this disease can be greatly reduced or prevented though the institution, early in life, of a low‐phenylalanine diet. However, the effectiveness of dietary therapy is often limited by poor compliance, especially by adolescents or young adults. This can lead to declines in neuropsychological function. The potential of somatic gene therapy for the treatment of PKU is therefore worth exploring. We discuss three different vector systems. Recombinant retroviral vectors and DNA/protein complexes can efficiently transduce PAH‐ deficient hepatocytes in vitro, but their present application is limited by their low transduction efficiency in vivo. In contrast, infusing a recombinant adenoviral vector expressing the human PAH cDNA into the portal circulation of PAH‐deficient mice restores 10%‐80% of normal hepatic PAH activity and completely normalizes serum phenylalanine levels. At present, this effect is transient and readministration has no further effect. However, this result suggests that PKU and other monogenic hepatic deficiencies can be completely corrected by somatic gene therapy when more persistent vectors are developed. © 1995 Wiley‐Liss, Inc.
Rodent models of mental retardation: Self‐injury, aberrant behavior, and stress
Authors: Tessel Richard E. , Schroeder Stephen R. , Stodgell Christopher J. , Loupe Pippa S.
Published: June 2005

This paper reviews the research on three animal models related to self‐injurious behavior (SIB), stereotypy, and aggression and their susceptibility to stress. These studies support the importance of stress and differences in organic dysfunction in the etiology, maintenance, and topography of SIB and their relationship to stereotypy and aggression. Several organic risk factors associated with mental retardation also increase the susceptibility to manifestation of SIB and related behaviors. © 1995 Wiley‐Liss, Inc.
Analysis of FMRP, the protein deficient in fragile X syndrome
Authors: Small Kersten , Warren Stephen T.
Published: June 2005

Fragile X syndrome results from a massive trinucleotide repeat expansion in the 5′ untranslated region of the gene FMR1. Methylation of FMR1 occurs as a result of this expansion, causing transcriptional silencing. Therefore, the absence of FMR protein (FMRP) appears to result in fragile X syndrome. Characterization of the gene and its expression, as well as the cellular localization and functional properties of the protein, provide insight into how the absence of FMRP results in mental retardation and the related phenotype. Alternative splicing of FMR1 transcripts leads to protein isoforms and suggests that this cell is functionally diverse. Among vertebrates, FMRP is highly conserved at the amino acid level and localizes mainly to the cytoplasm. The presence of two protein sequence motifs, the RGG box and the KH domain, suggests that FMRP is an RNA‐binding protein. Direct experimentation shows that FMRP is capable of binding its own RNA in vitro, as well as a subset of brain‐derived messages. Further understanding of how these interactions take place and identification of those genes having messages that interact will provide insight into the mechanisms of cognitive function in humans. © 1995 Wiley‐Liss, Inc.
Females with fragile X syndrome: A review of the effects of an abnormal FMR1 gene
Authors: Lachiewicz Ave M.
Published: June 2005

In 1980, Turner et al. described a sample of females affected with fragile X syndrome and recommended that all females with mental retardation of unknown etiology be evaluated for this condition. Since then, much has been learned about fragile X syndrome and its effects on females. Although research has primarily focused on abnormal cognitive and emotional findings in a proportion of women, studies have also addressed the physical characteristics and specific findings of young girls. Some of the early results were puzzling because so little was understood about the genetics of this condition, but much has become clear since the gene was sequenced in 1991. Many questions about this condition are still unanswered, but are likely to be addressed in the near future. This article highlights major advances made during the past 10 years with regard to females having fragile X syndrome. © 1995 Wiley‐Liss, Inc.
Gene–teratogen interaction: Potentiation of actinomycin D teratogenesis in the house mouse by the lethal gene brachyury
Authors: Winfield John B. , Bennett Dorothea
Published: June 2005

Single intraperitoneal injections of actinomycin D (70 μg/kg female body weight) on day 6 1/4 of gestation yielded no abnormal embryos in wild‐type mice. Fifty percent of embryos similarly exposed to actinomycin D but obtained from matings in which one of the parents was heterozygous for Brachyury (T), a semidominant lethal gene at the T locus on linkage group IX, were abnormal. The abnormal embryos were presumably heterozygotes for T. Mesodermal derivatives and neural tissue were predominantly affected. Morphologically these abnormalities were very similar to those already described in homozygotes of T and early‐acting lethal t alleles. In a similar study trypan blue was also tested. This agent did not interact with T in producing abnormalities, and the abnormal development observed differed from that seen with actinomycin D. The results were interpreted as indicating that actinomycin D summates with T in converting T + heterozygotes into phenocopies of T/T homozygotes and early‐acting lethal t‐allele homozygous embryos.
Early biochemical changes in the embryonic rat heart after teratogen treatment
Authors: Overman Dennis O. , Beaudoin Allan R.
Published: June 2005

The effects on mucopolysaccharide synthesis in isolated embryonic rat hearts of in vivo and/or in vitro 6‐aminonicotinamide, dietary‐induced folic acid deficiency, aminopterin, and trypan blue were investigated using uptake of 35S‐sodium sulfate to measure the rate of mucopolysaccharide synthesis. Intraperitoneal injection of 6‐aminonicotinamide on day 11 of gestation caused inhibition of mucopolysaccharide synthesis which was most pronounced at day 13. A similar effect followed in vitro 6‐aminonicotinamide treatment. Maternal folic acid deficiency on days 9–11 of pregnancy caused decreased mucopolysaccharide synthesis in embryonic hearts at day 14. In vitro treatment with the folic acid antagonist aminopterin inhibited the rate of synthesis on days 13–16. In vivo trypan blue on day 9 of pregnancy had no effect on the rate of mucopolysaccharide synthesis. However, in vitro trypan blue treatment of embryonic hearts resulted in a marked depression in synthetic rate. Aminopterin and 6‐aminonicotinamide had no noticeable effect on the rate of protein synthesis in isolated embryonic hearts as determined by measurement of 3H‐leucine incorporation. Thus mucopolysaccharide synthesis in isolated embryonic rat hearts was susceptible to the action of the teratogens used. It is postulated that these teratogens act by blocking a biochemical reaction in the synthesis of mucopolysaccharides and are not affecting the cellular machinery necessary for general protein synthesis.
Teratogenic effects of short‐term and transitory zinc deficiency in rats
Authors: Hurley Lucille S. , Gowan Jean , Swenerton Helene
Published: June 2005

Female rats fed a zinc‐deficient diet during pregnancy (days 0 to 21) had impaired reproduction and a high incidence of congenitally malformed young even though they had been fed a normal diet adequate in zinc until the beginning of gestation. With a deficiency from days 0 to 21 of pregnancy 41% of the implantation sites were resorbed, full‐term young weighed about half that of controls, and 90% of the fetuses showed gross malformations affecting every organ system. These results were similar to those found previously with females fed a zinc‐low diet from weaning. The fetal malformations were specifically due to a maternal dietary deficiency of zinc rather than to reduced food intake since females fed restricted amounts of a zinc‐supplemented diet had normal young. Shorter periods of deficiency were also teratogenic. With a deficiency from days 0 to 10 of pregnancy 22% of the young were malformed, and from days 0 to 12, 56% were malformed. When the zinc‐deficient regime was imposed from days 6 to 14 of pregnancy almost half of the young were abnormal. Transitory periods of deficiency altered the incidences of the anomalies observed in accordance with the developmental events occurring at the time the deficiency was imposed. The rapid and severe effects of even relatively short periods of zinc deficiency on fetal development suggest that the pregnant rat cannot mobilize zinc from body stores in amounts sufficient to supply the needs of developing fetuses.
In vitro and in vivo X‐irradiation of preimplantation mouse embryos
Authors: Fisher D. L. , Smithberg M.
Published: June 2005

Two‐day‐old strain 129/SvSl mouse embryos obtained by induced superovulation were exposed to various doses of X‐rays in vitro and in vivo and cultured from the 4‐cell to the blastocyst stage. The LD50 for blastocyst development 48 h after in vitro irradiation was 300 R and following in vivo irradiation was 600 R. Blastulation occurred in over 80% of the cultured sham‐irradiated control embryos. Treated and control embryos that blastulated after 48 h of culture were transplanted to nulliparous adult 2‐day pseudo‐pregnant 129/SvSl females and examined 15 days later. Approximately 70% of implanting control blastocysts developed into fetuses. Significantly fewer fetuses developed after in vitro exposure to more than 73 R. No fetal development occurred following in vitro irradiation with more than 170 R. No indication of implantation was observed for embryos irradiated in vitro with more than 267 R. Fetal development occurred following in vivo irradiation with 388 R. It appears that it required twice as much in vivo irradiation as in vitro irradiation to produce equivalent lethality for the early mouse embryo. No significant gross abnormalities were observed in preterm fetuses following embryonic irradiation in vitro or in vivo, but there was significant weight‐gain impairment in fetuses developing from transplanted embryos irradiated in vitro with 73 R or more.
Inhibitory effect of corticoids on the proliferative pattern in mouse palatal processes
Authors: Jelínek Richard , Dostál Miroslav
Published: June 2005

The formation of the secondary palate in mice is accompanied by intensive mitotic activity, which is mainly concentrated at the medial edges of the palatal processes. In control H‐Velaz randombred fetuses the mitotic activity culminated approximately 24 h before palatal‐shelf horizontalization, so that the period of intensive cell proliferation coincided with the period when cleft palate could be induced by cortisone administration. Effects of teratogenic doses of corticoids, injected directly into amniotic sac of embryos on day 13 (0.3 mg hydrocortisone) or im to pregnant females on day 12 (7.5 mg cortisone acetate), on the proliferative peak in palatal processes were studied using intraamniotic injection of colchicine. Counts of colchicine‐blocked mitoses in histological serial sections revealed both a significant decrease in overall mitotic density and a posterior shift of the proliferative peak in the palatal processes of fetuses treated with doses of corticoids producing cleft palate.
Cytotoxic effects of 6‐mercaptopurine on the limb‐bud blastemal cells of rat embryos
Authors: Merker H. J. , Pospisil M. , Mewes P.
Published: June 2005

On day 12 of pregnancy Wistar rats were each given a single ip injection of 5, 8, 16, 25, or 50 mg/kg 6‐mercaptopurine. The embryos were removed 1, 2, 3, 5, 6, 10, 24, 48, or 72 h after injection or on day 20 and studied by light and electron microscopy. After 25 or 50 mg/kg all embryos showed no mineralization in the lower extremities. By electron microscopy condensation, shrinking, and fragmentation of cells in the limb bud blastema could be seen after 5 h. The fragments were phagocytosed and broken down by neighboring cells or remained in the extracellular space. After 25 or 50 mg/kg the damage was so extensive that the number of undamaged cells and of cells transforming into phagocytes, was not sufficient to remove the debris or to compensate for the defect by mitotic activity. Epithelial cells, nerves, and blood vessels, show no morphological signs of damage. The “critical period” was the time cartilage just starts developing, i.e., when the blastema begins to differentiate.
Effects of three teratogens on development of arteries in the secondary palate in rats
Authors: Diewert V. M.
Published: June 2005

Development of the arterial vasculature in the secondary palate was studied in Sprague‐Dawley rat fetuses treated with vitamin A plus cortisone, 6‐aminonicotinamide (6‐AN), and X‐rays. Most of the control and teratogen‐treated fetuses were India‐ink injected for study of the palatine vasculature; others were histologically sectioned in the coronal plane. All 3 teratogens affected development of the lateral palatine processes and arterial vasculature. Vitamin A plus cortisone produced severe palate deformities. The palatine processes were composed of multiple horizontal and vertical processes containing abnormal epithelial and cartilaginous components. The palatine arteries remained widely separated in the maxillary area of the palate but narrowed to form a “V” pattern in the premaxillary area. 6‐AN and X‐rays delayed development of arterial patterns and the palatine processes, and decreased growth of the lateral palatine processes. After reorientation the palatine arteries remained fairly widely separated in fetuses with cleft palate.
Effects of hydrocortisone acetate on the development of chicken embryos
Authors: Goel Suresh C. , Jurand A.
Published: June 2005

Hydrocortisone acetate (1–10 mg/egg), when injected into the extraembryonic celom of 3‐ or 4‐day chicken embryos, caused necrosis in limb‐bud mesoderm after further incubation for 24 h. The necrotic areas usually appeared in the central and subapical mesoderm. Similar treatment of 4‐day embryos with a higher dose (7.5 mg/egg) caused, in addition, hemorrhage in limb buds, micromelia, and slight growth retardation. The mechanism of the resulting necrosis and phagocytosis are discussed.
Evaluation of the teratogenic effects of hydrazine, methylhydrazine, and dimethylhydrazine on embryos of Xenopus laevis, the South African Clawed Toad
Authors: Greenhouse Gerald
Published: June 2005

Xenopus laevis embryos were exposed to hydrazine and its methylated derivatives, (mono)methylhydrazine, 1,2‐dimethylhydrazine (SDMH), and 1,1‐dimethylhydrazine (UDMH). Concentrations of hydrazine, methylhydrazine, and UDMH in excess of 10 mg/1 were teratogenic; SDMH was teratogenic at concentrations of 50 mg/1 or greater. Exposure to lower concentrations permitted survival and development into normal larvae. The period of embryogenesis during which exposure to hydrazine was teratogenic was during neurulation. Exposure to these compounds at later or earlier periods affected viability but was not teratogenic. The malformations affected the head, trunk, and tail. The most common abnormality observed was tail kinks. Other abnormalities were microcephaly, cyclopia, shortening of the trunk, and edema. All malformed embryos also had abnormal notochords. The possible relation of notochordal abnormality to the pathogenesis of other malformations is discussed.
Comparative susceptibilities of pregnant, nonpregnant, and lactating hamsters to infections with H‐1 and reoviruses
Authors: Kilham Lawrence , Margolis George
Published: June 2005

Pregnant and lactating hamsters were inoculated with reovirus type 3 and H‐1 virus to determine whether they had any special susceptibility as compared with nonpregnant controls; whole blood, liver, and uterus were tested for virus on successive days after inoculation. Results showed that both agents proliferated to highest titers in pregnant as well as in lactating animals. These results were most striking with reovirus, which propagated to only a limited extent in controls and hamsters in the first half of gestation, although developing to high titers in the second half. A feature of the experiments was the ability of both agents to infect the postpartum uterus. Uterine infections, which appear to have importance for both rubella and cytomegaloviruses, should it would seem, be considered in relation to any viruses capable of inducing fetal infections or congenital anomalies.
Methylmercury: Teratogenic and lethal effects in frog embryos
Authors: Dial Norman A.
Published: June 2005

Rana pipiens embryos at the cleavage, blastula, gastrula, and neural‐plate stages of development were treated with methylmercuric chloride in concentrations of 0.5–200 parts per billion (ppb) to determine embryocidal and teratogenic effects. Concentrations of 40 ppb and above were lethal to embryos treated during the cleavage stage. Embryos at the blastula, gastrula, and neural‐plate stages were treated for 5 days with 5–30 ppb; 5 ppb had only minor effects, 10, 15, and 20 ppb caused various defects (exogastrulae, poor tail development, poor general development) and increased death rates related to exposure time and concentration, and embryos treated with 30 ppb had a high frequency of defects after 24 h and all died by the end of the 3rd day. Individual tolerances to methylmercury of various degrees were observed.
Kidney agenesis, hypoplastic left heart, and rib and vertebral anomalies in the fetus of a diabetic mother
Authors: Harris M. J. , Yasuda M. , Poland B. J.
Published: June 2005

A male human fetus of 83 mm crown‐rump length was removed by hysterotomy from a diabetic woman. It was normal externally but had bilateral kidney agenesis, a hypoplastic left heart, vertebral fusion on the left side, and other cervical and thoracic vertebral and rib anomalies. Possible syndromes and their relevance to prenatal diagnosis are discussed.
Teratogenicity studies with methotrexate, aminopterin, and acetylsalicylic acid in domestic cats
Authors: Khera K. S.
Published: June 2005

Pregnancy was timed in cats following induced ovulation. Methotrexate, (0.5 mg/kg), aminopterin, (0.1 mg/kg), and acetylsalicylic acid, (25 or 50 mg/kg) were administered orally in gelatin capsules in single daily doses on different days of gestation, methotrexate (MTX) on days 11‒14, 14‒17, or 17‒20, aminopterin on day 12, 14, or 16, and acetylsalicylic acid (ASA) on days 10‒15 or 15‒20. Maternal toxicity was produced only by MTX. MTX given on days 11‒14 and 14‒17 produced high frequencies of malformations including umbilical hernia. Aminopterin caused no conclusive teratogenic response. An overall increased frequency of anomalies occurred after 50 mg/kg ASA but no single anomaly predominated.
In vitro development of postimplantation rat embryos cultured on dialyzed rat serum
Authors: Gunberg David L.
Published: June 2005

Attempts to culture postimplantation rat embryos on defined media have not been successful although they grow well when cultured on homologous serum. As a first step in the search for factors in serum that support growth and differentiation of such cultured preparations the following experiments were undertaken. Six‐somite rat embryos were cultured on whole serum, dialyzed serum, or the buffered salt solution (BSS) used for dialysis. Additional experiments were conducted utilizing BSS supplemented with glucose or dialyzed serum supplemented with glucose, mannose, fructose, or pyruvate. Of the media tested only glucose‐supplemented dialyzed serum maintained development at a level comparable to that obtained with whole serum. Further preliminary studies with combined supplementation and metabolic poisoning suggested that anaerobic glycolysis is essential for the in‐vitro growth and differentiation of these preparations.
Studies of the etiology of thalidomide dysmorphogenesis
Authors: McBride W. G.
Published: June 2005

Thalidomide was administered to pregnant rabbits in dosages of 150–250 mg/kg/day on days 8–12 of gestation. These females produced 40 offspring, 21 of which were deformed. Four control females produced 34 offspring, none of which was deformed. The C6 and C7 ganglia of day‒13, ‒15, ‒17, and ‒21 control and experimental embryos and fetuses were examined electron microscopically. Degenerative changes were found in the neurons and axons of dorsal root ganglia in day‒13 experimental embryos, i.e., at least 16 h before the earliest signs of thalidomide dysmelia have been reported in rabbits (Vickers, '67). Since the dorsal root ganglia form in rabbits on days 11 and 12 the changes evident at day 13 indicate that degeneration of neurons and axons may be a pathogenetic factor in thalidomide‐induced peripheral deformities.
Descriptive epidemiology of small‐bowel atresia in metropolitan Atlanta
Authors: Safra Mark J. , Oakley Godfrey P. , Erickson J. David
Published: June 2005

The epidemiological characteristics are presented of 46 children with small‐bowel atresia, ascertained over a 6‐year period by an active, population‐based birth defect surveillance program in Atlanta, Georgia. The malformation occurred at a rate of 2.7/10,000 livebirths. The previously reported association of duodenal atresia and Down syndrome was confirmed. No instances of familial association were noted, nor was any excessive prenatal exposure to drugs found. Thirty‐two instances of isolated small‐bowel atresia were analyzed in detail. The frequency of the isolated defect for blacks was twice that for whites because of a higher rate for black females. The isolated defect was commonest in the winter months. The relation between isolated small‐bowel atresia, birth weight, and mortality was discussed. This small series cannot readily be subdivided into distinct epidemiological groups on the basis of the location of the atretic lesions along the length of the small boweL.
Trisomy 18 and cyclopia
Authors: Lang Arnold P. , Schlager F. Michael , Gardner H. Allen
Published: June 2005

A stillborn male infant with cyclopia, holoprosencephaly, extracephalic malformations, and trisomy 18 is described. The importance of chromosome studies in infants with severe congenital malformations is discussed.
Cardiovascular malformations in Oryzias latipes embryos treated with 2,4,5‐trichlorophenoxyacetic acid (2,4,5‐T)
Authors: Schreiweis Donald O. , Murray Gordon J.
Published: June 2005

Exposure of fertilized Oryzias latipes eggs to concentrations of 2,4,5‒trichlorophenoxyacetic acid up to 14 ppm had no gross developmental effects. Exposure to concentrations above 14 ppm resulted in multiple malformations of the heart and blood vessels. Embryos failed to hatch when exposed to concentrations above 25 ppm.