摘要:

AbstractThis case‐control study examines the relation of cryptorchidism to central nervous system dysfunction. Elevated odd ratios were found for cerebral palsy (RR = 34), low IQ (RR = 2.7), and low motor function measured by the Bayley test (RR = 3.6). Low IQ and cerebral palsy were independent risk factors for cryptorchidism. Breech labor (RR = 2.6), a gestation<34 weeks (RR = 2.0), and being a twin (RR = 4.1) were also independent risks. Other risk factors were estrogen use by the mother (RR = 3.3) and a maternal Quetelet index<24 (RR = 1.6). All of these risks were statistically significant. These factors suggest that cryptorchidism may be caused either by sex steroid action directly on the testes or by CNS damage, which in turn causes suppression of pituitary gonadotropins. The increased occurrence of cryptorchidism in twins and small babies indicates that retarded general fetal development can be another mechanism for maldescent of the teste

ISSN:0040-3709    

DOI:10.1002/tera.1420370403

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe effects of multiple maternal subcutaneous injections of tellurium dioxide (TeO2) suspended in olive oil (0–1,000 μmol/kg) from day 15 to day 19 of gestation were evaluated in the Wistar rat. External and internal soft‐tissue examinations were performed on day 20 fetuses. Multiple maternal injections, at doses higher than 10 μmol/kg, resulted in a dose‐related appearance of hydrocephalus, edema, exophthalmia, ocular hemorrhage, umbilical hernia, undescended testis, and small kidneys in fetuses on day 20 of gestation. At 500 μmol/kg, reduction in maternal weight gain was also observed. At this level, the incidence of the above anomalies was 100%. The 100 μmol/kg dose of Te, which did not produce apparent maternal toxic responses, resulted in a 100% incidence of hydrocephalus and edema but no fetal mortality. Thus, tellurium can be teratogenic to the rat fetus without concomitant maternal toxicity. Also, the fetal period may be more sensitive than the organogenic period for the induction of hydrocephalus. Such evidence is consistent with the development of the choroid plexus and an effect of TeO2on the production/resorption of cerebrospi

ISSN:0040-3709    

DOI:10.1002/tera.1420370404

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

年代:1988

数据来源: WILEY

摘要:

AbstractTo investigate the effect of chronic ethanol exposure on the embryonic chick heart, chick embryos were exposed daily to one of seven graded doses of ethanol or to saline only (shams) from 0 to 96 hr of incubation. One hour before and after exposure at 72 hr, and 1 hr before and after exposure at 96 hr, embryos were analyzed for changes in heart function, embryo tissue ethanol content, occurrence of anomalies, and embryo weights. At both 71 and 73 hr of incubation (during cardiogenesis), when compared to shams, heart rate (HR) in embryos receiving ethanol doses>0.0375 ml increased significantly (P<.05) with commensurate increases in injected ethanol. Additionally, at 73 hr, depressed cardiac contractility, measured as shortening fraction, was noted at doses ≥ .0375 when compared to shams. While slight increases in shortening fraction (SF) across dose were noted at 95 and 97 hr, only random doses were statistically significant from shams, with no specific trend in either HR or SF at this postcardiogenesis stage. Within each time group, gas chromatography analysis of embryo tissue ethanol content demonstrated a linear relationship between dose injected and tissue ethanol content retrieved. With increasing dose and stage, viability decreased. Weights of ethanol‐injected embryos were not significantly different from shams within each time group. Our studies of the response of the embryonic chick heart to ethanol indicate both dose and stage susceptibility, with greater susceptibility to ethanol injury during active cardiogene

ISSN:0040-3709    

DOI:10.1002/tera.1420370405

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

年代:1988

数据来源: WILEY

摘要:

AbstractFurosemide, a loop diuretic, was orally administered to pregnant Crj: CD (SD) rats at a dose of 300 mg/kg once on day 16 of gestation. Cartilage bone double staining of day 17 fetuses revealed a delay in ossification. Characteristic rib deformities were not seen until day 18 of gestation. Concomitant with this observation were reductions in the amount of amniotic fluid, compared to controls, on day 18 of gestation and thereafter. When isoxsuprine HCl (2 mg/kg, b.i.d.), a uterine muscle relaxant, was additionally injected ip to pregnant rats on days 17–19 of gestation, the incidence of wavy ribs was significantly (P≤ .05) less than that seen after treatment with furosemide alone. These observations indicate that the myometrial constriction plays a significant role in the induction of furosemide‐induced wavy

ISSN:0040-3709    

DOI:10.1002/tera.1420370406

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

年代:1988

数据来源: WILEY

摘要:

AbstractThirty litters of C57BL 6J mice were administered intraperitoneally one of four doses (0, 500, 750, and 1,000 mg/kg maternal weight) of acetazolamide on day 9 of gestation. The fetuses were removed on day 18 and fixed, stained, cleared, and examined for the pattern of malformations. The forelimb postaxial limb deficiency was the most common abnormality, but forelimb postaxial polydactyly and a postaxial deficiency in the hindlimb were also observed. Males were significantly more likely to be malformed than females at all doses, in contrast to the predominance of females observed in rat fetuses exposed to acetazolamide (Scott et al.:Teratology 6:239–240, '73). The occurrence of limb malformations did not correlate with maternal weight loss, the birth weight of the fetus, or the position of the fetus in the uterus. A “litter effect” was demonstrated in that there was a nonuniform distribution of litters with different proportions of malformed fe

ISSN:0040-3709    

DOI:10.1002/tera.1420370407

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

年代:1988

数据来源: WILEY

摘要:

AbstractSecalonic acid D (SAD) induces cleft palate in the developing mouse by an unknown mechanism. To investigate possible roles of cyclic nucleotides (cAMP and cGMP) in the teratogenesis of SAD, cAMP and cGMP levels were measured in the extracts of fetal palates of gestational age 130through 1612(dayshours). Fetuses were obtained from pregnant CD‐1 mice treated on day 110of gestation, with either 5% (wt./vol.) sodium bicarbonate (NaHCO3, control) or 30 mg/kg of SAD in 5% NaHCO3, intraperitoneally (i.p.). Radioimmunoassay was used to quantitate cyclic nucleotide levels. Cyclic AMP levels peaked on day 1412of gestation in controls. In the SAD group there was a significant decrease in cAMP levels on days 1312and 140of gestation and a decrease of 30% in total cAMP on days 130through 140of gestation, with little or no change at the peak on day 1412. On day 1512, however, the SAD group had a 68% increase in palatal cAMP level over the control. Control levels of cGMP appeared to follow a diurnal pattern reaching maximal levels at the end of the dark cycle. In contrast, SAD decreased the cGMP level by 31% on day 1312(P<0.05) and increased it 100% above that of the control level on day 150(P<0.01). Total cGMP during days 150through 1612of gestation was 33% higher than control (P<0.01). The number of clefts in the SAD group was significantly higher at all points following palate closure in the control fetuses (140through 1612) with values ranging from 20% to 34% versus 0% in the control (P<0.01–0.005). Morphological changes on days 130through 150indicated a failure of shelf elevation in middle and posterior palatal regions of SAD‐treated fetuses. These results suggest that the induction of cleft palate by SAD is associated with dynamic changes (initial decrease followed by later increase), in vivo, in established cyclic nucleotide patterns and support a mechanistic role for cyclic nucleotide‐mediated cellular processes in normal as well as abnormal palate deve

ISSN:0040-3709    

DOI:10.1002/tera.1420370408

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

年代:1988

数据来源: WILEY

摘要:

AbstractTheThair pin(Thp) mutation is a deletion of 5 centimorgans of chromosome 17 in the mouse. When the mutant chromosome is passed to the fetus through the female, the heterozygous fetuses (Thp/+) die in utero. If the chromosome is passed through the male, the heterozygotes are viable and display a short‐tailed phenotype. These maternally derived mutant embryos provide an excellent model system to study the effects of an incomplete female genome on development. The results reported here describe the findings of a pathological study of the affected fetuses from day 14 of development to birth. These observations indicate that the maternally derivedThpfetuses die in utero of congestive heart failure. The mutant fetuses displayed an enlarged heart, primarily the right side, and other cardiovascular abnormalities including ventricular septal defects, aortic stenosis, pulmonary artery dilation, and dilation of the venous circulatory system. The fetuses also displayed abnormal accumulation of extrafetal fluid in the visceral yolk sac and amion, as well as massive subcutaneous edema and ascites. TheThpfetuses were often pale and anemic, and they showed a decreased number of red blood cells per unit volume of blood and an increase in circulating nucleated red blood cells. Defects in the development of the labyrinthine and spongiotrophoblast regions of the placenta were also observed. The pathogenesis of the defects is discusse

ISSN:0040-3709    

DOI:10.1002/tera.1420370409

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

年代:1988

数据来源: WILEY

摘要:

AbstractPrevious experimental studies have implicated a genetic component in the induction of malformations in the offspring of diabetic rats. We have compared the outcome of diabetic pregnancy in two outbred (sub)strains of Sprague‐Dawley rats (with low incidence [H] and high incidence [U]of skeletal malformations in the offspring) and hybrids between them. The fetuses of diabetic H mothers had no skeletal malformations and the lowest frequency of resorptions (8–9%), regardless of embryo type (H/H or H/U). When the diabetic mother was U or from the hybrid strain (H/U) and the offspring were of the mixed H/U type, we found increased resorption (16–21%) and skeletal malformation (3–5%) rates. If instead the embryos contained a major U genome [either U/U or U/(H/U)], further increased resorptions (23–30%) and skeletal malformations (17–19%) resulted. The H/H and U/U embryonic susceptibility to defined teratogens (3–6 mg/ml D‐glucose, 4–8 mM B‐hydroxybutyrate) were compared in whole embryo culture and found to be similar, suggesting that the malformations occurring in vivo may have a different etiology than those found in vitro. In the rat model studied, diabetes in the mother appears to cause a disturbance of early stages of embryogenesis in genetically predisposed embryos. This early disturbance results in skeletal malformations and seems to require inducing factor(s) in addition to increased levels of D‐glucose and B‐hydroxybutyrate. The findings are in concert with the notion of a mixed genetic‐environmental etiology of malformation

ISSN:0040-3709    

DOI:10.1002/tera.1420370410

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

年代:1988

数据来源: WILEY

摘要:

AbstractEleven of the common inbred strains of the mouse were surveyed for their teratogenic response to acetazolamide that was administered three times per os at 1,000 mg/kg (9A.M.and 4P.M.on day 9 and 9A.M.on day 10). The products of conception were examined for gross malformations on day 15. One strain, SJL/J, exhibited maternal toxicity to the dosage regime and was excluded from the survey. Five strains exhibited significantly increased resorption rates after treatment. All strains responded with the expected malformation of postaxial forelimb ectrodactyly with a right‐sided predominance. Nine of the strains could be assigned to one of four mutually exclusive classes of frequency of ectrodactyly and the tenth strain (BALB/cByJ) showed overlap between the two intermediate classes. The data suggest major genes determine the difference in sensitivity to ectrodactyly rather than a polygenic mode of inheritance. Induced cleft lip was found in four strains and one of these strains, SWR/J, exhibited a significantly higher frequency. The strain differences in sensitivity to induced resorption, forelimb ectrodactyly, and cleft lip were genetically independent. A reciprocal cross study was conducted with five of the strains from the four classes of frequency of ectrodactyly response in order to determine gene action. A significant maternal effect on the ectrodactyly response was found only with one of the strain pairs in the ten sets of reciprocal crosses with the five strains. When there was a significant difference between two strains, the F1embryos exhibited dominance of relative resistance to ectrodactyly. The directional dominance of relative resistance to acetazolamide‐induced ectrodactyly suggests that regulatory genes control the embryonic differences in frequency of ectrodactyly response to acetazolamide. By analogy with other metric traits of development that exhibit directional dominance, the genetic variation in ectrodactyly response that has been observed so far in the mouse embryo may not be involved with the primary target of acetazolamide teratogene

ISSN:0040-3709    

DOI:10.1002/tera.1420370411

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

年代:1988

数据来源: WILEY

摘要:

AbstractThe splotch gene (Sp) and all‐trans retinoic acid (RA) interact to cause spina bifida in mouse embryos. To investigate the mechanisms of action of the two, the spinal regions ofSphomozygotes, RA‐treated wild‐type, and control wild‐type embryos were examined histologically by light microscopy on day 9 of gestation. The mean numbers of cells per section in the neural tube, mesoderm, and notochord were determined, along with the percentages of mitotic and pyknotic nuclei and the numbers of migrating neural crest cells. As well, the effect ofSpand RA on the extracellular matrix was studied histochemically with Alcian blue staining for glycosaminoglycans. The main defect inSphomozygotes was a marked reduction in the number of migrating neural crest cells and the amount of extracellular matrix around the neural tube. Retinoic acid, on the other hand, caused a number of disruptions in the embryo, including abnormalities in the position of the notochord and the shape of the neural tube.Spand RA delay neural tube closure and thus cause neural tube defects, through different mechanisms. However, the combined effects of the gene and teratogen on the embryo lead to a greater inhibition of neural tube closure than when either is present sep

ISSN:0040-3709    

DOI:10.1002/tera.1420370412

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

年代:1988

数据来源: WILEY