bluuebunny/crossref_metadata_2025_split huggingface dataset:
Perinatal thymocyte antigen expression and postnatal immune development altered by gestational exposure to tetrachlorodibenzo‐p‐dioxin (TCDD)
Authors: Holladay S. D. , Lindstrom P. , Blaylock B. L. , Comment C. E. , Germolec D. R. , Heindell J. J. , Luster M. I. 
Published: June 2005

AbstractIn utero exposure to the environmental contaminant 2,3,7,8–tetrachlorodibenzo‐p‐dioxin (TCDD) was found to alter expression of murine thymocyte fetal cell‐surface markers. Pregnant mice were treated (via gavage) with 0, 1.5, or 3.0 μ TCDD/kg/day in corn oil on gestational days (gd) 6–14. Offspring were examined on gd 18 and postnatally on d6, d14, and d21, and at 7, 8, and 10 weeks of age. Severe thymic atrophy and cellular depletion were found both pre‐ and postnatally in TCDD‐exposed mice. Immunocytochemical localization of the Thy 1.2 antigen on gd 18 thymocytes revealed no TCDD‐related changes in cellular distribution. Flow cytometric analysis, however, indicated that the TCDD treatment resulted in a significant decrease in the percentage of CD4+8+ fetal thymocytes, as well as significantly increased CD4−8− and CD4−8+ thymocytes. The increased CD4−8+ population after TCDD was not from induction of Ts cells. At 7–8 weeks postnatally, no differences existed between control and treatment groups in mitogen responses and antibody plaque response. However, altered thymocyte antigen expression was found to correlate with altered postnatal immune function, as evidenced by decreased cytotoxic T lymphocyte response at 8 weeks of age. Taken together, these results indicate that immunosuppression following prenatal exposure to TCDD can be readily detected by qualitative and quantitative changes in the cell surface phenotype of fetal thymocytes. Furthermore, the observed altered distribution suggests that TCDD inhibits normal thymocyte maturational processes.
Reversible effects of triamcinolone and lack of effects with aspirin or L‐656,224 on external genitalia of male Sprague‐Dawley rats exposed in utero
Authors: Wise L. David , Vetter Christine M. , Anderson Charles A. , Antonello Joseph M. , Clark Robert L. 
Published: June 2005

AbstractInhibitors of the arachidonic acid cascade were given to pregnant rats during the critical period for morphogenesis of the external genitalia. Groups treated subcutaneously (s.c.) with 0.1 or 0.25 mg/kg/day of triamcinolone acetonide (TA) on gestational days (GD) 14–19 had male fetuses on GD 20 with moderate decreases in absolute anogenital distance (AGD), but gross and histological examinations revealed no alterations to the genital tubercle (i.e., no hypospadias). The s.c. coadministration of arachidonic acid at 100 mg/kg/day had minimal to no effect on AGD in the TA‐exposed groups. No effect on AGD was observed in male fetuses from groups administered aspirin orally at 150 mg/kg/day, and only a 6% decrease was observed in the 300‐mg/kg/day group. Neither TA nor aspirin adversely affected AGD of female fetuses. In another study, TA was administered on GD 11–19 at dose levels of 0.05 and 0.1 mg/kg/day, and dams were allowed to deliver. High‐dose male offspring examined on postcoitum day (PCD) 23, had moderate decreases in AGD. In both studies with TA, there were also significant decreases in offspring weights. The contribution of the decreased weight to the decrease in absolute AGD was examined by a variety of methods (ratio of AGD to cube root of weight or biparietal distance, comparison to weight‐matched controls, and covariance analysis). We conclude that TA caused a specific decrease in AGD on GD 20 that was largely reversed by PCD 23. When examined as adults (8 weeks old), the external genitalia of TA‐exposed offspring were normal. Thus, the TA‐induced decreases in AGD on GD 20 did not predict irreversible malformation. TA also caused other effects, which included a somewhat flattened genital tubercle and apparently thinned and glossy skin between the tubercle and the anus in both sexes on GD 20 and PCD 23, but not as adults. In addition, there were high pup mortality and high incidences of micrognathia and omphalocele (in the 0.25‐mg/kg/day group only). Aspirin at 75 or 150 mg/kg/day and a specific lipoxygenase inhibitor (L‐656,224) at 1,000 or 2,000 mg/kg/day were also administered from GD 14 to 19, and no offspring effects were observed. Thus, of the three agents that potentially inhibit the arachidonic acid cascade, only triamcinolone produced moderate effects on rat external genitalia that were largely reversible. Compared with previously reported results using B10.A mice (Gupta and Goldman, '86), these data indicate that the Sprague‐Dawley rat is much less sensitive to the effects of aspirin and glucocorticoids on anogenital distance and, therefore, prostaglandins are unlikely to be primary mediators of androgen‐initiated external masculinization in this rat strain.
Aspirin dose‐dependently reduces alcohol‐induced birth defects and prostaglandin E levels in mice
Authors: Randall Carrie L. , Anton Raymond F. , Becker Howard C. , Hale Robert L. , Ekblad Ulla 
Published: June 2005

AbstractThe purpose of the present study was threefold. The first purpose was to determine if aspirin (ASA) decreases alcohol‐induced birth defects in mice in a dose‐dependent fashion. The second purpose was to see if the antagonism of alcohol‐induced birth defects afforded by ASA pretreatment was related to dose‐dependent decreases in prostaglandin E (PGE) levels in uterine/embryo tissue. The third purpose was to determine if ASA pretreatment altered maternal blood alcohol level. In experiments 1 and 2, pregnant C57BL/6J mice were administered ASA (0, 18.75, 37.5, 75, 150, or 300 mg/kg) on gestation day 10. One hour following the subcutaneous injection of ASA, mice received alcohol (5.8 g/kg) or an isocaloric sucrose solution intragastrically. In experiment 1 the incidence of birth defects was assessed in fetuses delivered by caesarean section on gestation day 19. In experiment 2 uterine/embryo tissue samples were collected on gestation day 10 1 hr following alcohol intubation for subsequent PGE analysis. In experiment 3 blood samples were taken at five time points following alcohol intubation from separate groups of alcohol‐treated pregnant mice pretreated with 150 mg/kg ASA or vehicle. The results from the three experiments indicated that 1) ASA dose‐dependently reduced the frequency of alcohol‐induced birth defects in fetuses examined at gestation day 19, (2) ASA decreased the levels of PGE in gestation day 10 uterine/embryo tissue in a similar dose‐dependent fashion, and 3) ASA pretreatment did not significantly influence maternal blood alcohol levels. These results provide additional support for the hypothesis that PGs may play an important role in mediating the teratogenic actions of alcohol.
Limb reduction defects in humans associated with prenatal isotretinoin exposure
Authors: Rizzo Renata , Lammer Edward J. , Parano Enrico , Pavone Lorenzo , Argyle J. Craig 
Published: June 2005

AbstractRetinoic acid has long been used to induce limb reductions defects in experimental animal studies. No limb malformations, however, have been reported among malformed retinoic acid‐exposed human fetuses from case reports or epidemiologic studies. We report a child and a fetus with limb reduction malformations following maternal use of isotretinoin (13‐cis‐retinoic acid) during the first trimester of pregnancy. The child had a unilaterally absent clavicle and nearly absent scapula, with a short humerus and short, synostotic forearm bones. He also had ventriculomegaly and developmental delay, minor dysmorphic facial features, and a short sternum with a sterno‐umbilical raphe. The fetus had a unilaterally absent thumb with normal proximal bony structures. Other findings included hydrocephalus, craniofacial anomalies, thymic agenesis, supracristal ventricular septal defect, single umbilical artery, anal and vaginal atresia, and urethral agenesis with dysplastic, multicystic kidneys. Although the limb malformations were quite dissimilar, a number of anomalies that are frequently found among isotretinoin‐exposed fetuses/infants were present in both cases. This increases the probability that retinoic acid caused these limb defects, but a causal association cannot be conclusively drawn on the basis of these two retrospective case reports.
Inhibition of isotretinoin teratogenicity by acetylsalicylic acid pretreatment in mice
Authors: Kubow Stan 
Published: June 2005

AbstractAlthough isotretinoin (ITR) has been suggested to cause malformations via cytopathic effects on embryonic cells, the molecular mechanisms of ITR cytotoxicity in teratogenesis are not clear. Since ITR undergoes metabolism by prostaglandin synthase to a potentially cytotoxic peroxyl free radical, the possible role of prostaglandin synthase metabolism as a modulator of ITR teratogenicity was evaluated. Craniofacial and limb abnormalities were noted in fetuses on day 18.5 of gestation following administration of ITR to pregnant CD‐1 mice in a three dose regime of 100 mg/kg at 4 hr intervals on day 10.5 of gestation (plug day = day 0.5 of gestation). Mice were also treated with acetylsalicylic acid (ASA), an irreversible inhibitor of the cyclooxygenase component of prostaglandin synthase, at doses of 20 and 60 mg/kg body weight 2 hr prior to each ITR dose. ASA pretreatment of mice receiving ITR treatment showed a dose‐dependent decrease in the overall incidence of malformations, number of defects per fetus, and the incidence of specific craniofacial and limb defects. Equivalent doses of ASA given to control mice did not cause malformations or alter the incidence of resorptions. These results demonstrate that ASA is able to ameliorate the teratogenic effects of ITR observed in fetal mice near term and indicate that prostaglandin metabolism could play a mechanistic role in ITR teratogenicity.
Benign cystic ovarian teratomas with prostatic tissue: A report of two cases
Authors: Uzoaru I. , Akang E. E. U. , Aghadiuno P. U. , Nadimpalli V. R. 
Published: June 2005

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 discussed.
In vitro development of rat embryos undergoing organogenesis in heparin‐plasma
Authors: Kesby Gregory J. 
Published: June 2005

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‐embryo culture.
Demographic, reproductive, medical, and environmental factors in relation to gastroschisis
Authors: Werler Martha M. , Mitchell Allen A. , Shapiro Samuel 
Published: June 2005

AbstractTo identify risk factors for gastroschisis other than drug use in pregnancy, an analysis of data collected in a case‐control surveillance program of birth defects (1976‐1990) was conducted. Drug use is considered in Werler et al.,Teratology, 45:361‐367, 1992. Maternal demographic, reproductive, and medical factors, and first trimester environmental exposures, were compared between 76 gastroschisis cases and 2,581 malformed controls. A strong inverse association was found for maternal age: relative to women 30 years or older, relative risks for 25‐29, 20‐24, and <20‐year‐old women were 1.7, 5.4, and 16, respectively. Multivariate relative risks (and 95% confidence intervals) for alcohol use were as follows: for 1‐5 drinks per week, 1.6 (0.7‐3.4); for ⩾6 drinks per week, 2.5 (0.9‐6.8); for a maximum of 1‐4 drinks at any one time, 0.8 (0.4‐1.6); and for a maximum of ⩽5 drinks, 2.8 (1.2‐6.5). With the effect of age taken into account, no associations were identified for cigarette smoking, consumption of caffeinated or decaffeinated coffee, unplanned pregnancy, 12 or less years of education, or a parity of two or more. Other medical and reproductive factors, including weight gain, vaginal bleeding, nausea or vomiting, influenza, “other” infection, and history of spontaneous abortion or elective abortion did not increase the risk.
Morphometric analysis of heterozygote dancer mice predisposed to 6‐aminonicotinamide‐induced cleft lip
Authors: Jacobson Debbie , Trasler Daphne G. 
Published: June 2005

AbstractMid‐facial development is an extremely complex process involving coordinated events and precise timing. Cleft lip (CL) may result fro the failed fusion of the lateral and medial nasal processes in the developing embryo. It has been postulated that spontaneous CL in the A/J strain of mice may be due to a predisposing face shape (Trasler, '68). This hypothesis was examined in mutant mice susceptible to teratogen‐induced CL. Mice carrying the dancer (Dc) mutation in the heterozygous state rarely develop CL, whereas 90% of homozygotes (Dc/Dc) develop CL. Outcrossed heterozygotes show elevated susceptibility to 6‐aminonicotinamide (6AN)‐induced CL (Trasler et al., '84) and these were used to investigate face shape as a predisposing factor. Dc/+ and + / + males were mated to R stock females, and embryos were collected on day 10/21 hr, when the nasal placodes are approximately at the oblong or crescent stage. Total nasal process areas and volumes, medial and lateral process areas and volumes, and medial jut lengths were measured from histological sections, and comparisons made between the two populations. The results indicate that compared to +/+ control, heads of embryos from the Dc/ + cross have significantly smaller mean total process areas and volumes (P<0.005), mean lateral process areas and volumes (P⩾0.005), mean medial process area and volumes (P⩾0.01), mean maximum head diameter (P⩾0.02), but similarly sized medial juts and crown rump lengths. Correlations between maximum head diameter and process size indicate that the Dc mutation may hinder normal development of the nasal processes. These reduced nasal processes may explain the underlying predisposition to 6AN‐induced CL.
Mouse conceptuses have a limited capacity to elevate the mRNA level of cellular retinoid binding proteins in response to teratogenic doses of retinoic acid
Authors: Harnish Douglas C. , Soprano Kenneth J. , Soprano Dianne Robert 
Published: June 2005

AbstractIn these studies, we wished to determine the effect of teratogenic doses of retinoic acid on the expression of cellular retinoic acid binding protein I (CRABP‐I) mRNA, cellular retinoic acid binding protein II (CRABP‐II) mRNA, cellular retinol binding protein I (CRBP‐I) mRNA, and cellular retinol binding protein II (CRBP‐II) mRNA in mouse conceptuses. Levels of CRABP‐II mRNA and CRBP‐I mRNA were modestly elevated (2.5‐fold and 1.5‐fold, respectively) in 9‐day gestation conceptuses following treatment of dams with 100 mg/kg b.w. of retinoic acid. These levels were elevated by 6 hr following treatment and remained elevated unitl 48 and 24 hr. respectively. Two other retinoids, etretinate and retinoyl β‐glucuronide, also moderately elevated CRABP‐II mRNA and CRBP‐I mRNA levels in conceptuses. In contrast, the levels of CRABP‐I mRNA in the conceptuses remained unaffected by treatment with any of these three retinoids. These results demonstrate that conceptuses have a limited capacity to elevate the cellular retinoid binding proteins mRNA levels and presumably the synthesis of their respective proteins in response to high, teratogenic doses of retinoic acid. As a result, an excess of free retinoic acid becomes available to the nuclear retinoic acid receptors, which may lead to inappropriate gene expression and eventual maldevelopment. © 1992 Wiley‐Liss, Inc.
Inner ear malformations induced by isotretinoin in hamster fetuses
Authors: Burk Dorothy T. , Willhite Calvin C. 
Published: June 2005

AbstractInner ear malformations induced in anotic hamster fetuses following maternal treatment with 50 mg/kg isotretinoin (13‐cis‐retinoic acid) on gestational day 8 are described. Computer‐assisted three dimensional reconstruction was used. Two general types of defective vestibulocochlear development were seen. Defects were bilateral and correlated with extent of middle ear deficiency and severity of mandibular defects. In the more severely affected fetuses the inner ear was limited to an epithelial sac with occasional small projections, no apparent innervation and a correspondingly reduced otic capsule. In most of the fetuses examined the inner ear was less severely affected and was characterized by a reduction in the number of semicircular ducts and alterations in the size and shape of the cochlear duct. These defects are similar to those seen in a child with the isotretinoin embryopathy. Pathogenesis may result from a direct effect on otic epithelium or from faulty inductive interactions with the rhombencephalon or with periotic neural crest cells. © 1992 Wiley‐Liss, Inc.
Developmental stages of the CD® (Sprague‐Dawley) rat skeleton after maternal exposure to ethylene glycol
Authors: Marr Melissa C. , Price Catherine J. , Myers Christina B. , Morrissey Richard E. 
Published: June 2005

AbstractEthylene glycol (EG), a chemical which causes skeletal malformations in rats, was administered by gavage to sperm positive CD® rats on gestational days (gd) 6 through 15 at doses of 0 or 2,500 mg/kg/day to assess its effects on the pre‐ and postnatal skeletal development. Dams and fetuses/pups were killed on gd 18, 20, postnatal day (pnd) 1, 4, 14, 21, or 63, and offspring were double‐stained for examination of skeletal malformations and degree of ossification of rapidly developing skeletal districts. No difference in gestational day of delivery between controls and the EG‐treated dams was seen. Fetal weights per litter were significantly decreased with EG treatment in both the gd 18 and 20 groups. Pup body weight on pnd 1 was significantly below controls; however, EG had no effect on pup body weight on pnd 4–63. The percentage of fetuses/pups with skeletal malformations per litter was significantly increased after EG exposure for all time points except at pnd 63, with a predominance of axial skeletal defects. The percentages of total ossification, of sternabrae ossified, and of vertabral centra ossified were significantly reduced in the EG groups on gd 20 and on pnd 1–21, but not on gd 18 or on pnd 63. When the ossification data were subjected to statistical analysis with fetal/pup weights as a covariate, the values for EG‐exposed pups on gd 20 were not statistically significantly different from the control values. The reduced ossification values for EG‐exposed pups on pnd 1–21 retained statistical significance even after covariate analysis. There was no effect of dose or body weight on ossification of fore‐ or hindlimb digits. In conclusion, the differences in incidence of skeletal alterations observed prenatally and through pnd 21 were not evident by pnd 63, suggesting that perinatal skeletal abnormalities may not always be permanent. © 1992 Wiley‐Liss, Inc.
Genetic differences in heat‐induced tolerance to cadmium in cultured mouse embryos are not correlated with changes in a 68‐kD heat shock protein
Authors: Kapron‐Brás Carolyn M. , Hales Barbara F. 
Published: June 2005

AbstractHeat‐induced cross‐tolerance to cadmium was investigated in two inbred strains of mice, BALB/c and SWV, using a whole embryo culture system. Embryos were exposed to a pretreatment of 5 min at 43°C and subsequently to an embryotoxic concentration of cadmium, 1.75 μM. The two types of embryos responded differently to the heat pretreatment, as cross‐tolerance was induced in SWV but not in BALB/c mice. In SWV embryos, prior exposure to 43°C for 5 min essentially eliminated the negative effects of cadmium on embryonic development and growth. However, in BALB/c embryos, no protection was observed. The variation in development of cross‐tolerance in embryos from the two strains of mice was not correlated with differences in the induction of a 68‐kD heat‐shock protein (hsp68). There was a rapid increase in this protein in both strains after the initial heat exposure but no excess induction in the SWV strain that developed tolerance. The induction of hsp68 is therefore not sufficient to elicit cross‐tolerance, and other mechanisms are likely to be important in the protective response of the embryo. © 1992 Wiley‐Liss, Inc.
Developmental toxicity of dichloroacetate in the rat
Authors: Smith M. K. , Randall J. L. , Read E. J. , Stober J. A. 
Published: June 2005

AbstractDichloroacetic acid (DCA) is a principal by‐product of the chlorine disinfection of water containing humic and fulvic acids, and is also a drug of interest in the therapeutic management of metabolic disorders. The developmental effects of DCA were evaluated in the pregnant Long‐Evans rat. In two separate studies, animals were dosed by oral intubation on gestation days 6–15 (plug = 0) with 0, 900, 1,400 1,900 or 2,400 mg/kg/day and 0, 14, 140, or 400 mg/kg/day. The vehicle control was distilled water. Maternal observations included clinical signs, weight change, and gross evaluation of organ weights and uterine contents at necropsy (day 20). Corpora lutea were counted and uteri stained for implantation sites. Live fetuses were examined for external, skeletal, and soft tissue malformations. Seven dams died during treatment (1,400 mg 1/19, 1,900 mg 2/19, 2,400 mg 4/21), and maternal weight gain was reduced at all except the lowest treatment levels. Liver, spleen, and kidney weights increased in a dose‐related manner. The mean percentage of resorbed implants per litter was significantly elevated at ≥900 mg/kg/day. Live fetuses showed dose‐dependent reductions in weight and length at doses above 140 mg/kg. Statistically significant frequencies of soft tissue malformations ranged from 2.6% (140 mg/kg) to 73% (2,400 mg/kg). These were principally in the cardiovascular system and predominantly comprised defects between the ascending aorta and the right ventricle. Skeletal malformations were not observed in significant numbers in any dose group. We conclude that the no observed adverse effect level (NOAEL) for the developmental toxicity of DCA in the rat was 14 mg/kg/day, a dose level that produced obvious treatment‐related maternal effects. © 1992 Wiley‐Liss, Inc.