ISSN:0040-3709    

DOI:10.1002/tera.1420470102

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.1420470103

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.1420470104

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.1420470105

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

年代:1993

数据来源: WILEY

摘要:

AbstractPrevious investigations had shown that i.p. injection of 2′‐deoxycoformycin (dCF; pentostatin; 5 mg/kg) on either E7 or E8 into pregnant mice results in a 61–81% resorption rate at E17. The incidence of visible gross malformations among the surviving conceptuses was exceptionally low (3%) at the time of necropsy on E17 and was unrelated to dCF dose (Knudsen et al., Teratology,40:5–626, '89; Teratology,45:91–103, '92). These findings demonstrated the embryotoxicity of dCF but provided no clues as to the site(s) of dCF action. To define the lesion site(s), we have now examined embryos at 72 h(E10), 96 h (E11), and 120 h (E12) following administration of a highly embryotoxic dose of 5 mg dCF/kg to dams on E7. Deoxycoformycin caused multiple abnormalities and growth retardation, and the temporal sequence between maximal abnormal embryo incidence and resorption frequency was established. The quantitative data show that the maximal occurrence of abnormal embryos on E10 (71%) was followed by a maximal resorption rate on E12 (78%). There was a strong correlation (r = −0.82;P<0.05) between the rapid decline of percent abnormal embryos over E10–E12 and the simultaneous increase in resorption rate, with linear regression analysis showing nearly equal but opposite slopes (−31.2% vs. +35.8% per gestational day, respectively). This suggests that one or more of the abnormalities seen at E10 is associated with the death and resorption of the embryo at E12. The dCF treatment perturbed a wide spectrum of developmental events, including neural tube closure, craniofacial and limb development, turning of the embryo, and growth retardation. None of the individual abnormalities, however, can quantitatively account for the high percentage of dead and resorbed embryos. Therefore, the specific cause of dCF‐induced embryolethality is not clear. There is evidence both for direct dCF toxicity at specific embryonic sites as well as for a generalized retardation in the rate of development. © 19

ISSN:0040-3709    

DOI:10.1002/tera.1420470106

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

年代:1993

数据来源: WILEY

摘要:

AbstractWhen single large equimolar doses (0.38–0.41 mmol/kg BW) of all‐transretinoic acid (RA), all‐transretinoyl β‐glucose (RBGL), and all‐transretinoyl β‐glucuronide (RBG) are administered orally in oil on day 8.5 of pregnancy to Sprague‐Dawley rats, RA and RBGL proved highly teratogenic, whereas RBG was not. Indeed, fetuses from RBG‐treated dams were 16% heavier (P<0.01) than control fetuses. After dosing with RA and RBGL, RA appeared in large amounts within 0.5 h in the maternal plasma and within 1.0 h in the embryo. In contrast, orally administered RBG seemed to be absorbed much more slowly, to be converted very slowly to RA, and not to accumulate either as RBG or as RA in the embryo. When incubated in vitro with embryos and attached membranes, however, both all‐transRBG and all‐transRA were partially converted to 13‐cisRA. The nonteratogenicity of RBG, in contrast to RA, seems to be due to a much slower rate of GI absorption, a slow rate of hydrolysis to RA, a limited passage from the maternal circulation into the embryo, and a lower inherent toxicity.

ISSN:0040-3709    

DOI:10.1002/tera.1420470107

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

年代:1993

数据来源: WILEY

摘要:

AbstractThe teratogenic potential of 13‐cis retinoic acid (13‐cis RA) was further assessed in cynomolgus macaques (Macaca fascicularis) following exposure to two different regimens during the preorganogenic period to determine the influence of time of treatment on the 13‐cis RA malformation syndrome established previously (Hummler et al., Teratology,42:263–272, 1990). In experiment (Exp) 1, 13‐cis RA was orally administered once daily (2.5 mg/kg) on gestational day (GD) 16–25 and twice daily (2 × 2.5 mg/kg) on GD 26–27. In Exp 2, the same oral dose was administered once daily on GD 10–20 and twice daily on GD 21–24. Although the ear was affected at about the same incidence (6/9, 67%) in Exp 1 as previously reported, the defects were less severe. Except for hypoplastic vermis of the cerebellum (2/9, 22%), no other defects were seen. In Exp 2, the teratogenic effects of 13‐cis RA on the craniofacial skeleton (1/9, 11%), external ear (5/9, 56%), and heart (2/9, 22%) were similar to that reported by Hummler et al.; however, no thymus or cerebellar malformations were observed. Analysis of the three different treatments (GD 16–27 in Exp 1, GD 10–24 in Exp 2, and GD 10–27 in Hummler et al.) suggests that the sensitive periods in the macaque are 1) craniofacial skeleton and heart GD 10–24, 2) thymus and cerebellum>GD 24, and 3) external ear GD 16–24, although the defects are less severe following the shorter exposure. Exposure to 13‐cis RA preceding onset of morphological organogenesis appears to be a requirement for 13‐cis RA embryopathy in the cynomolgus monkey. The external ear appears to be both a uniquely sensitive biomarker for 13‐cis RA teratogenicity and an indicator of embryotoxic severity. Finally, the longer period of drug administration (2.5 mg/kg, GD 10–25, and 2 × 2.5 mg/kg, GD 26–27) used by Hummler et al. is more suited to assessment of 13‐cis RA teratogenicity in macaques due to greater concordance with the 13‐cis

ISSN:0040-3709    

DOI:10.1002/tera.1420470108

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

年代:1993

数据来源: WILEY

摘要:

AbstractDuring 1984–1989, 116 cases of omphalocele and 42 cases of gastroschisis were detected among 736,760 consecutive births in the area covered by five Italian congenital malformation registries. The prevalence rate was 1.6 per 10,000 for omphalocele and 0.6 per 10,000 for gastroschisis. Three additional cases were detected among spontaneous abortions, giving a total of 117 cases of omphalocele and 44 of gastroschisis. No variations in prevalence rates were observed among registries. A cluster of omphalocele was found in 1989 in Firenze. All cases were sporadic except for one infant with two sibs with Beck‐with–Wiedemann syndrome. A predominance of male infants was observed for both defects. This study confirms the very young maternal age for isolated gastroschisis as compared to that for omphalocele and controls. Birth weight and the percentage of small‐for‐date is different among isolated gastroschisis, omphalocele and controls. Associated anomalies occurred in 45 cases of omphalocele and 11 cases of gastroschisis. Our data confirm the association of omphalocele with trisomies 13 and 18. Twelve cases of omphalocele and gastroschisis with associated limb defects were classified as limb body wall complex. The possible differences in etiopathology between omphalocele and gastroschisis, both isolated and associated, are discussed. © 1993 Wiley

ISSN:0040-3709    

DOI:10.1002/tera.1420470109

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

年代:1993

数据来源: WILEY

摘要:

AbstractThis study examined the effects of ethanol (EtOH) on mouse preimplantation development using an in vitro culture method. Embryos at the 1‐cell, 2‐cell, or 4‐cell stage were exposed for 24 h to medium containing EtOH, then further cultured without EtOH to determine their ability to form blastocysts and to eventually hatch from the zona pellucida. EtOH exposure either arrested or enhanced normal development, depending on dose and embryonic stage of exposure. Exposure of 1‐cell and 2‐cell embryos to 1.6% (w/v) EtOH decreased blastocyst formation and hatching, and exposure of 1‐cell embryos to 0.4% EtOH inhibited their development. At 0.1%, EtOH had an opposite effect, causing an increase in the percent blastocyst formation of treated 1‐cell and 2‐cell embryos. Neither inhibition nor stimulation of blastocyst formation occurred in 4‐cell embryos exposed to 0.1–1.6% EtOH. Using an in vitro outgrowth model of implantation, embryos that reached the blastocyst stage were further tested for their ability to produce differentiated trophoblast cells. Blastocysts previously exposed to 0.1% EtOH during the 1‐cell stage appeared to form adhesive trophoblasts earlier than control embryos, indicating that EtOH exposure can induce precocious differentiation of the trophoblast cells. The EtOH treated blastocysts contained significantly more cells than control blastocysts. These results indicate that EtOH can alter preimplantation development by either inhibiting or accelerating cell growth and differentiation.

ISSN:0040-3709    

DOI:10.1002/tera.1420470110

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

年代:1993

数据来源: WILEY

摘要:

AbstractFirst degree relatives of infants with bilateral renal agenesis or dysplasia have an increased risk of renal abnormalities including renal agenesis. We report a family in which four successive offspring exhibited a previously undescribed combination of congenital lethal renal disorders: bilateral renal dysplasia, megalocystis secondary to urethral obstruction and, sirenomelia with associated renal agenesis. © 1993 Wiley‐Liss, I

ISSN:0040-3709    

DOI:10.1002/tera.1420470111

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

年代:1993

数据来源: WILEY