摘要:

AbstractAn excess of structural defects occurs in monozygotic twins compared to dizygotic twins or singletons. Among these defects the acardius acephalus or chorangiopagus parasiticus is one of the most rare and severe and a possible cause of pathology to the other twin. Ovulation induction by clomiphene causes an increased frequency of multiple gestation and possibly of monozygotic multiple pregnancy. In the present report, we describe a prenatally diagnosed and autopsied case of acardius acephalus from a pregnancy established after ovulation induction by clomiphene. Approximately 1.4% of pregnancies are accomplished after use of ovulation inducing medication in the Netherlands. A possible etiological role of clomiphene justifies close monitoring of future cases. © 1993 Wiley‐Liss, I

ISSN:0040-3709    

DOI:10.1002/tera.1420470402

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

年代:1993

数据来源: WILEY

摘要:

AbstractClomiphene citrate was administered to female mice at different doses and different times prior to ovulation, in the preimplantation period after ovulation, and after implantation. Pregnancy outcome was determined on day 15 of gestation, when the number of implantations and resorptions were calculated relative to the number of ovulations, and fetuses were assessed for size and stage of development and morphological abnormalities. Preovulatory administration of clomiphene citrate caused decreased implantation rates and growth retardation of surviving fetuses, the degree of the effect being dependent on the dose and the time of drug injection relative to ovulation. The implantation rate was lowest, and the degree of fetal growth retardation highest, when clomiphene citrate was administered immediately before ovulation. An increased incidence of exencephaly was found in the fetuses of females injected with clomiphene citrate prior to ovulation. Transfer of blastocysts from treated mice to untreated fosters showed the effect of clomiphene citrate on implantation and fetal growth to be predominantly mediated through the female reproductive tract, rather than a direct effect on the embryo itself. Administration of clomiphene citrate in the preimplantational period resulted in complete inhibition of implantation, while the only effect when administration was after implantation was a slight reduction in fetal weight. These results indicate that preovulatory clomiphene citrate impairs uterine function, which has an indirect effect on the growth and development of the postimplantation embryo. © 1993 Wiley‐Liss, I

ISSN:0040-3709    

DOI:10.1002/tera.1420470403

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

年代:1993

数据来源: WILEY

摘要:

AbstractEllagic acid (EA) is a naturally occurring plant phenol that was recently demonstrated to protect cultured rat embryos from the embryotoxic effects of N‐methyl‐N‐nitrosourea (MNU). The teratogenic mechanism of action of MNU, as well as other methylating agents, is debated: both cell death and mutation have been proposed. In some model systems, EA has been reported to selectively decrease the mutagenic DNA adduct O6‐methylguanine (O6MG) when compared to the cytotoxic DNA adduct N7‐methylguanine (N7MG). The present study was initiated to determine 1) the distribution of14C‐EA and3H‐MNU in the rat whole embryo culture model system and 2) the effects of EA on MNU‐induced DNA adduct formation in this model system.14C‐EA (50 μM for 2 hr, known embryoprotective concentration; no MNU added) was used to demonstrate access of EA to the embryo within the 2 hr exposure period. The majority of EA (99.5%) remained in the media while tissue concentrations of 57.0 and 47.9 pmol/mg were attained in the yolk sacs and embryos, respectively. Similarly, MNU (75 μM for 1 hr, known effective concentration; no EA added) was distributed between the media, yolk sacs, and embryos at 99.7%, 73.7 and 112.9 pmol/mg, respectively. When non‐radiolabeled EA (50 μM for 2 hr) was used to protect embryos prior to exposure to3H‐MNU (75 μM for 1 hr), the distribution of MNU in the model system was unchanged. When O6MG and N7MG addjuction rates in yolk sac DNA, embryo DNA, and pooled data were compared between protected (50 μM EA for 2 hr followed by 75 μM MNU for 1 hr), and non‐protected tissues (vehicle for 2 hr followed by 75 μM MNU for 1 hr), EA decreased O6MG formation by 35.2–49.7% while N7MG was not decreased. The decreases in O6MG formation were only statistically significant (P<0.05) when yolk sac and embryo data were pooled. EA apparently interrupts the embryotoxic pathogenesis of MNU by decreasing O6MG formation within the embryo and/or

ISSN:0040-3709    

DOI:10.1002/tera.1420470404

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe purpose of this paper is to present a statistical model for analyzing the joint effects of exposure on fetal death, fetal weight, and malformation in a developmental toxicity study. In addition to allowing for the usual litter effect, the model allows for correlations between different outcomes measured on the same fetus. Fitting the model requires first focusing on non‐live outcomes by modeling the probability of fetal death or resorption as a function of dose. Then outcomes among live fetuses are modeled using a two‐stage regression approach. The first stage models fetal weight as a function of dose and the second stage models fetal malformation as a function of dose, as well as residuals from the weight model. The regression coefficients from the malformation model have intuitive interpretations in terms of correlations between littermates and between different outcomes measured within the same fetus. Not only does the approach provide a useful way to investigate the relationship between adverse fetal outcomes, it also yields a natural framework for conducting quantitative risk assessment. A procedure is proposed for quantifying overall risk by incorporating the three outcomes in order to estimate safe dose levels and corresponding lower confidence limits. The method is illustrated using data from an experiment in mice conducted through the National Toxicology Program. © 1993 Wiley‐Lis

ISSN:0040-3709    

DOI:10.1002/tera.1420470405

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

年代:1993

数据来源: WILEY

摘要:

AbstractAn empirical dose‐response model can generally be found for bioassay data, which provides a mathematical relationship between the incidence of a developmental malformation and dose of a toxicant in the experimental dose range. If biological principles and data can be used in the formulation of the dose‐response model, the estimation of the incidence of malformations outside of the experimental dose range may be improved. In this paper, exponential growth of morphological structures in rodents during gestation is assumed. Further, it is assumed that some structural malformations are the result of reduced or delayed growth and the incidence of structurally normal fetuses is proportional to fetal weight raised to a power. When the exponential growth rate constant is reduced by dose raised to a power, a Weibull dose‐response function is obtained. When the exponential growth rate constant is modeled by a polynomial function of dose, a polynomial‐exponential dose‐response model is obtained. The Weibull and the polynomial‐exponential model, restricted to degrees from one up to the number of dosed groups, were fit to a database of bioassay data assembled fromTeratologyVol. 1 (1968) to Vol. 42 (1990). In general the two models gave similar results and often gave exactly the same fit. The linear term appeared in the polynomial‐exponential model in about one‐fourth of the cases and was not related to the background incidence. Published 1993 by

ISSN:0040-3709    

DOI:10.1002/tera.1420470406

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe two main maternal vessels that are a major, if not the entire, source of maternal blood for the mouse placenta are unique in possessing intraluminal valvular projections. The morphologic configuration of these projections suggests their potential to converge, diverge, and rotate blood currents flowing under systolic pressure. The intravascular occurrence of circularfibrin bodiescomposed of concentric fibrin strands coagulated from the plasma and almost no blood cellular elements in these strands lends credence to this concept. Histopathologic changes in the extraembryonic and embryonic tissues induced by an intraperitoneal injection of 250 or 500 mg/kg of 2‐methoxyethanol, or its metabolite, 2‐methoxyacetic acid, via oral gavage were determined 48 hr after dosing CD‐1 mice on day 11 of pregnancy. Both compounds caused 1) marked congestion and dilatation, associated with or without fibrinous occlusions, of the main maternal vessel of the placenta, 2) serosanguinous exudation and maternal hemorrhages from the placental periphery, 3) necrosis and desquamation involving the mesometrial surface or peripheral edge of the placenta, 4) translabyrinthine embryonic hemorrhage into the maternal circulation, and 5) embryonic hemorrhages into the exocoelomic, amniotic, and pericardial cavities. These lesions signify a disordered maternal circulation in the placenta suggestive of potentially serious pathologic effects. These lesions may play a role in the resorption, reduction in fetal body weight, and syndactyly or oligodactyly attributed to 2‐methoxyethanol and 2‐methoxyacetic acid. © 1993 Wiley

ISSN:0040-3709    

DOI:10.1002/tera.1420470407

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe B × H recombinant inbred strains of mice were used to undertake a genetic analysis of the maternal factors controlling the survival of trisomy 16 fetuses. The data presented indicate that the prevalence of trisomic fetuses on day 15 of gestation varies significantly with the genetic background of the mother. The strain difference in the frequency of trisomy appears to be the result of selective elimination of trisomic fetuses. Various statistical methods employed to elucidate the genetic architecture of the trait from the recombinant inbred strains data indicate that the number of loci involved in the selection process ranges from one to five. Linkage association with two loci has been found; however, with a low probability level (P= 0.292). © 1993 Wiley‐Liss,

ISSN:0040-3709    

DOI:10.1002/tera.1420470408

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe Brachyrrhine (Br) semidominant mouse mutant provides a useful model for studying factors responsible for midfacial hypoplasia. In order to determine early morphogenetic events responsible for midfacial hypoplasia in these mice, prenatal mutants must be differentiated from nonaffected littermates. The purpose of this study was to determine whether prenatal offspring fromBrmatings could be separated morphologically into groups of normal or midfacially deficient embryos. Thirty embryos resulting fromBrmatings were collected between day 15 and birth (Theiler stages 23–27). Qualitative observations on craniofacial morphology as well as renal morphology and histology suggested that embryos segregated into two distinct groups. External craniofacial and body measurements, collected from the embryos, as well as renal volumes, determined from computerized reconstructions of the kidneys, were subjected to quantitative analyses. A discriminant function analysis segregated the sample into two groups based primarily on midfacial length and renal volume. Bivariate regression analysis showed that midfacial length and renal volume differed significantly, and cranial length marginally so, between the two groups. The results indicate that a proportion of prenatal offspring fromBrmatings exhibits midfacial and renal hypoplasia and that these animals segregate completely from nonaffected embryos. © 1993 Wiley‐Liss,

ISSN:0040-3709    

DOI:10.1002/tera.1420470409

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

年代:1993

数据来源: WILEY

摘要:

AbstractSELH/Bc inbred mice have an abnormal mechanism of anterior neural tube closure and 10–20% of embryos have a lethal neural tube closure defect, exencephaly. Our previous studies have focused on this multifactorial threshold trait. However, SELH mice are also characterized by another trait that also shows non‐Mendelian transmission ratios, an ataxia recognized in juvenile and adult mice. Here we report our first genetic and morphological studies of the ataxia trait. Recent pedigree records for the SELH colony showed that 7% of the 467 weaned progeny from normal breeding pairs were ataxic; 17 of the 20 pairs produced ataxic progeny. This result was statistically consistent with the hypothesis that all SELH mice have the ataxic genotype, which is expressed in only 7% of them. Genetic studies of an outcross to a normal strain and the subsequent F2and testcross of the F2were also done. The results were consistent with a one or two gene locus cause of liability to ataxia in SELH mice. The genetic correlation between exencephaly production and ataxia production for a sample of nine F2males was 0.35, as expected if both traits are caused by the same genes, but was not statistically significant. In another approach, we examined the morphology of brains from normal and ataxic adult SELH mice. All 20 brains from non‐ataxic SELH mice were morphologically normal. In all 18 brains from ataxic SELH mice the cerebellum was abnormal, lacking the vermis, and characterized by a midline fissure. This phenotype in mice has previously been known in Mendelian mutants at theWnt‐1locus. Our observations in SELH mice suggest that these cerebellar defects can also show multifactorial threshold patterns of occurrence. Because the site of origin of the cerebellum is the site of maximal delay in neural tube closure in SELH mice, the exencephaly and ataxia may share a common genetic etiology. © 1993 Wiley

ISSN:0040-3709    

DOI:10.1002/tera.1420470410

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

年代:1993

数据来源: WILEY

ISSN:0040-3709    

DOI:10.1002/tera.1420470411

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

年代:1993

数据来源: WILEY