摘要:

AbstractWe report two cases of the rare occurrence of prostatic epithelium in ovarian teratomas with associated transitional epithelium in one of the cases. This association of prostatic tissue with urothelium tends to reinforce the well‐established embryogenetic derivation of the prostate from the urogenital sinus. Local hormonal events may influence the formation of prostatic tissue from female urothelium. The histologic and immunohistological differences between adult prostate as seen in our cases and female paraurethral (Skene's) glands are discusse

ISSN:0040-3709    

DOI:10.1002/tera.1420450302

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractA large‐scale developmental toxicology study of 2,4,5‐trichlorophenoxyacetic acid was conducted in four inbred strains and one outbred strain of mice. The most significant developmental effects observed were reduced fetal weight and increased incidences of cleft palate (malformation) and prenatal death (deaths/resorptions). The correlation coefficients among the proportion of deaths/resorptions, proportion of malformations, average fetal weights, and number of viable fetuses were investigated, with each variable measured on a per‐litter basis. Generally, the correlation coefficients between average fetal weight and number of viable fetuses were negative for the control and low‐dose groups in the C57BL/6, C3H/He, and BALB/c strains. Overall, the correlation coefficients between proportion of malformations and number of viable fetuses were not significant. The correlation coefficients between proportion of malformations and average fetal weight were negative for all but one case. The correlations were weak in the control and low‐dose groups, in which the malformation rates were very low, and were strong in the high‐dose groups. The correlation coefficients between proportion of deaths/resorptions and proportion of malformations were generally positive at the high doses; some negative correlations were observed in control and low‐dose groups. The correlation coefficients between proportion of deaths/resorptions and average fetal weight were negative for the A/JAX and CD‐1 strains. In summary, the strongest relationship observed was the negative correlation between fetal weight a

ISSN:0040-3709    

DOI:10.1002/tera.1420450303

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractIn previous experimental studies in rabbits, we have shown that vasodilating drugs (including nifedipine) cause distal digital defects. These defects were preceeded by edema, hemorrhage, and finally necrosis of the developed cartilage in the phalanges. The underlying mechanism is most likely a fetal hypoxic response, secondary to maternal hypotension and decreased uteroplacental blood flow. Since phenytoin is known to cause distal digital defects both in man and rabbits, we decided to compare the defects provoked by oral administration of phenytoin (100 mg/kg) versus nifedipine (8.3 mg/kg) to New Zealand White rabbits on days 6‐18 of gestation. In order to investigate phasespecificity, phenytoin (150 mg/kg) was given on days 14‐17. The result of single dose administration on day 16 of phenytoin (300 mg/kg) versus nifedipine (33.2 mg/kg) was also studied. In this latter experiment maternal heart rate was measured up to 21 hours after phenytoin administration. Phenytoin induced digital defects identical with those produced by nifedipine and caused marked maternal cardiodepression. The defects consisted of a reduction, absence, or abnormal structure of the distal phalanges. The distal phalanx of the fourth digit on the hindpaw was the first to be affected, with inclusion of other phalanges, both on the hind‐ and forepaws, with increasing dose. The sensitive period for induction and histological appearance of these defects was identical for phenytoin and nifedipine. These results suggest that vascular disruption due to a fetal hypoxic response lies behind phenytoin teratogenicity, as has been shown for vasodilators. A cardiodepressive action on the maternal and fetal hearts, possibly in combination with decreased uteroplacental blood flow, is discussed as a probable factor behind phenytoin teratogen

ISSN:0040-3709    

DOI:10.1002/tera.1420450304

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

Abstract4‐Oxo‐all‐trans‐retinoic acid, 4‐oxo‐13‐cis‐retinoic acid and all‐trans‐retinoyl‐β‐glucuronide were intraamniotically microinjected in rat embryos on day 10 of gestation and cultured until day 11.5. A comparison of the concentration‐effect relationships showed that the dysmorphogenic effects produced by these metabolites were qualitatively similar to those of parent all‐trans‐retinoic acid. Compared with all‐trans‐retinoic acid (300 ng/ml), the dysmorphogenic effects were elicited by a 2‐fold higher concentration of 4‐oxo‐all‐trans‐retinoic acid, an approximately 10‐fold higher concentration of 4‐oxo‐13‐cis‐retinoic acid and a 16‐fold higher concentration of all‐trans‐retinoyl‐β‐glucuronide. A surplus of uridine 5 ′‐diphospho‐glucuronic acid, microinjected together with 300 ng/ml all‐trans‐retinoic acid, decreased the observed embryotoxicity of all‐trans‐retinoic acid, suggesting the possibility of glucuronidation in tissues of the conceptus per se. The results of the study provide further support for the hypothesis that 4‐oxo‐all‐trans‐retinoic acid and all‐trans‐retinoic acid are, in c

ISSN:0040-3709    

DOI:10.1002/tera.1420450305

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractDihydrofolate reductase reduces folic acid to tetrahydrofolate as a prerequisite to one‐carbon metabolism, which is required for normal embryonic de novo DNA synthesis. The developmental toxicity of methotrexate (MTX) has been attributed to MTX's ability to inhibit the activity of dihydrofolate reductase and thereby indirectly suppress one‐carbon metabolism. The compound 1‐(p‐tosyl)‐3,4,4‐trimethylimidazolidine (TTI), which is structurally unrelated to folate, reestablishes one‐carbon metabolism by the biomimetic transfer of single carbon units. Whether the developmental toxicity of MTX is indeed caused via suppressed one‐carbon metabolism was tested in New Zealand white rabbits following concurrent maternal treatment with MTX and TTI. TTI reduced MTX developmental toxicity judged by increased mean fetal body weights, decreased percentage of malformed fetuses, and reduced incidences of major malformations. Two doses of TTI (90 mg/kg, each) at 1 hr prior to and 1 hr after MTX also reduced the developmental toxicity, but was no more effective than the single‐injection regimen. Treatment with TTI alone caused no developmental toxicity. Histologically, MTX caused enlarged intercellular spaces in limb bud mesenchyme that began at 6‐8 hr and increased in size until 16 hr. Mesenchymal nuclei appeared basophilic, with angular contours. Pretreatment with TTI delayed MTX‐induced histological changes until 20‐24 hr after MTX in 36‐50% of embryos and completely protected the remainder. The sequence of MTX‐induced changes was not altered among affected embryos, although the severity of the lesions did not appear as great. Saline‐only or TTI‐only treatments caused no alterations in limb buds. These data are consistent with the concept that impaired one‐carbon metabolism is indeed the fundamental process unde

ISSN:0040-3709    

DOI:10.1002/tera.1420450306

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe birth prevalence of Down syndrome (DS), although decreasing in parts of the world, is not known in many specific subpopulations. The rate of DS for live births was determined for a 15‐year period (1974‐1988) at the Los Angeles County‐University of Southern California Medical Center, which is a large public hospital serving a predominantly Latino population. DS was ascertained primarily by clinical monitoring of newborn infants. The overall rate of DS was 1.60/1,000 live births and had minimal fluctuation throughout the 15 years. The rate of DS for Latino births was 1.69/1,000 live births, 1.67 when adjusted for maternal age, and 1.75 when corrected for prenatal diagnosis. The high rate of DS in the Latino population was associated with advanced maternal ages and increased maternal‐age specific rates for DS, especially in the age ranges of 30 to 34 and 40 to 44 years, when compared with other

ISSN:0040-3709    

DOI:10.1002/tera.1420450307

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThis study examines the use of heparin‐plasma as a culture medium for mammalian postimplantation whole‐embryo culture. The growth and differentiation of head‐fold rat embryo explants over 48 hours in a standard serum medium was compared with development of same stage explants over 48 hours in a plasma medium prepared using sodium heparin.Heparin disrupted the morphological differentiation of embryos, in a concentration‐dependent manner, from 25 μg sodium heparin/ml media (i.e., 5 IU/ml media), with overall embryo growth being adversely affected from a concentration of 200 μg sodium heparin/ml media (i.e., 40 IU/ml media). Defects of cranial neural tube development were the first apparent structural anomalies resulting from culture in heparin media. Forebrain development was grossly abnormal and associated with failure of eye development. As the heparin concentration in media increased, the cephalic neural folds remained widely open and the edges became increasingly everted, although differentiation of the heart, otic primordia, and pharyngeal arch persisted. Similar concentration‐dependent dysmorphogenic effects were seen when embryos were cultured in the standard serum media with added heparin.A minimum heparin concentration of 100 μg sodium heparin/ml media (i.e., 20 IU/ml media) was required to effectively inhibit coagulation of the plasma medium over the 48 hour culture period. Although embryonic growth was not adversely affected at this heparin concentration, morphological differentiation was severely disrupted. Therefore, heparin is not a suitable anticoagulant for the preparation of plasma for use in postimplantation whole‐

ISSN:0040-3709    

DOI:10.1002/tera.1420450308

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractThe role of thyroid hormone in the control of cardiac and renal cell development was examined in neonatal rats made hyperthyroid by administration of triiodothyronine (T3, 0.1 mg/kg s.c. on postnatal days 1‐5) or hypothyroid by administration of propylthiouracil (PTU, 20 mg/kg s.c. given to dams on gestational day 17 through postnatal day 5 and to pups on postnatal days 1‐5). Indices of total cell number (total DNA per tissue), cell packing density (DNA per g tissue), and relative cell size (protein/DNA ratio) were evaluated from birth through young adulthood. PTU administration led to primary shortfalls in cell number that were of similar magnitude in both tissues, but persisted somewhat longer in the kidney than in the heart. Deficits in cell packing density and cell size in the hypothyroid animals were secondary to the effect on cell number, displaying smaller magnitudes of effect and a lag in appearance and disappearance of the deficits compared to that for total DNA; indeed, the phase in which tissues were restoring their cell numbers was accompanied byincreasedcell packing density, reflecting a more rapid restitution of cell numbers than tissue weight or cell size. In contrast to the relatively similar effects of PTU on developing cardiac and renal cells, the effects of T3 were selective for the heart. Although T3 caused general growth impairment, it evoked marked cardiac overgrowth that was accompanied by a striking increase in cell number and a small increase in cell size. The cardiac hyperplasia is unique to the developing animal, as post‐replicative heart cells in adult animals show only hypertrophy in response to thyroid hormone. The time course of appearance and disappearance of the effects of T3 on the indices of cardiac cell development suggested that the hormone shifted maturation such that cell replication was initiated and terminated earlier than in control animals. The results obtained in this study thus indicate that thyroid hormone plays two distinct and separable roles in modulation of cellular development: basal levels of hormone are required to maintain cell acquisition in all tissues but, in addition, there is a more specific role in cardiac cells in setting the timing of onset and disappearance of cell replic

ISSN:0040-3709    

DOI:10.1002/tera.1420450309

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

摘要:

AbstractTreatment of the father with the anticancer alkylating agent cyclophosphamide has negative effects on embryonic development in the rat. Four‐week treatment of male rats with a low dose of cyclophosphamide cause a dramatic, dose‐dependent increase in postimplantation death of the progeny. Several recent studies have indicated that the paternal genome is required for the development of the extraembryonic tissues. Thus, the purpose of this study was to determine which tissues of the implanting embryo were affected by paternal exposure to cyclophosphamide. Male Sprague‐Dawley rats were given cyclophosphamide (6 mg/kg/day) or saline by gavage and bred to untreated female rats after 4 weeks of treatment. Pregnant female rats were killed on day 7 of gestation, and implantation sites were dissected from the uterus, fixed, embedded in Epon for semithin serial sectioning, and stained for subsequent light microscopy. Strikingly, many of the implantation sites of affected embryos sired by treated males displayed an apparently normal trophectoderm enclosing a region of dying cells, containing dark‐stained pyknotic nuclei. Very few or no inner cell mass‐derived embryonic cells were present in these implantation sites. Therefore, there is a selective death of inner cell mass‐derived cells in day 7 implantation sites obtained from the progeny of cyclophosphamide‐treated males. The results of this study suggest that treatment of the male with cyclophosphamide can affect paternal genes specifically required for development of the inner cell mass cells of the embryo, without an apparent effect on those genes required for normal

ISSN:0040-3709    

DOI:10.1002/tera.1420450310

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420450311

出版商:Wiley Subscription Services, Inc., A Wiley Company    

年代:1992

数据来源: WILEY