Methods Used in Teratogenic Testing

Cook, Margaret J.; Fairweather, F.A.

doi:10.1258/002367768781082834

Cited by 11 publications

(3 citation statements)

References 6 publications

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“…The experiment was conducted as per the method described by Cook and Fairweather. 8 The female rats were allowed to mate with males in 2:1 ratio. Mating was confirmed by observing the vaginal smear and considered as '0' day of gestation.…”

Section: Methodsmentioning

confidence: 99%

Vitamin C ameliorates fluoride-induced embryotoxicity in pregnant rats

Verma

Sherlin²

2001

Hum Exp Toxicol

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Oral administration of sodium fluoride (40 mg/kg body weight) from day 6 to 19 of gestation caused, as compared to control, significant reductions in body weight, feed consumption, absolute uterine weight and number of implantations. Significantly higher incidence of skeletal (wavy ribs, 14th rib, <6 sternal centre, dumbell-shaped second and fifth sternebrae, incomplete ossification of skull and thickening of tibia) and visceral (subcutaneous haemorrhage) abnormalities were also observed in NaF-treated dams than that of control. Oral administration of vitamin C (50 mg/kg body weight) and vitamin E (2 mg/0.2 ml olive oil/animal/day) from day 6 to 19 of gestation along with NaF significantly ameliorates NaF-induced reductions in body weight, feed consumption, absolute uterine weight (only with vitamin E treatment) and number of implantations. As compared with NaF-treated alone, the total percentage of skeletal and visceral abnormalities were significantly lowered in fluoride plus vitamin C-treated animals. Vitamin E was less effective. These findings suggest that vitamin C significantly reduced the severity and incidence of fluoride-induced embryotoxicity in rats.

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Section: Methodsmentioning

confidence: 99%

Vitamin C ameliorates fluoride-induced embryotoxicity in pregnant rats

Verma

Sherlin²

2001

Hum Exp Toxicol

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“…The outburst of babies born with TE led to many changes in legislation concerning animal model research and drug commercialization around the world ( Daemmrich, 2002 ). In order to guarantee safe commercial liberation of a medicine, all drugs must be tested at least in two animal species, one non-rodent ( Cook and Fairweather, 1968 ), and results in these models must not be completely extrapolated to human species, once teratogenesis is not a species-specific process ( De Santis et al, 2004 ). Hence, studies of comparative teratogenesis like this are important to trace strategies for avoiding a new thalidomide tragedy.…”

Section: Discussionmentioning

confidence: 99%

Comparative Genomics Identifies Putative Interspecies Mechanisms Underlying Crbn-Sall4-Linked Thalidomide Embryopathy

et al. 2021

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The identification of thalidomide–Cereblon-induced SALL4 degradation has brought new understanding for thalidomide embryopathy (TE) differences across species. Some questions, however, regarding species variability, still remain. The aim of this study was to detect sequence divergences between species, affected or not by TE, and to evaluate the regulated gene co-expression in a murine model. Here, we performed a comparative analysis of proteins experimentally established as affected by thalidomide exposure, evaluating 14 species. The comparative analysis, regarding synteny, neighborhood, and protein conservation, was performed in 42 selected genes. Differential co-expression analysis was performed, using a publicly available assay, GSE61306, which evaluated mouse embryonic stem cells (mESC) exposed to thalidomide. The comparative analyses evidenced 20 genes in the upstream neighborhood of NOS3, which are different between the species who develop, or not, the classic TE phenotype. Considering protein sequence alignments, RECQL4, SALL4, CDH5, KDR, and NOS2 proteins had the biggest number of variants reported in unaffected species. In co-expression analysis, Crbn was a gene identified as a driver of the co-expression of other genes implicated in genetic, non-teratogenic, limb reduction defects (LRD), such as Tbx5, Esco2, Recql4, and Sall4; Crbn and Sall4 were shown to have a moderate co-expression correlation, which is affected after thalidomide exposure. Hence, even though the classic TE phenotype is not identified in mice, a deregulatory Crbn-induced mechanism is suggested in this animal. Functional studies are necessary, especially evaluating the genes responsible for LRD syndromes and their interaction with thalidomide–Cereblon.

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“…The pregnant females were transferred from the mating cages and rehoused in groups; each group consists of 10 animals as the following GI&GV designated as control groups for 15 th and 19 th days of gestation rspectively, while GII, GIII and GIV were treated with Fluoxetine HCl doses (0.052, 0.104 & 0.208 mg/mouse /day) From 6 th up to both 15 th days of gestation and GVI, GVII and GVIII were treated with Fluoxetine HCl doses (0.052, 0.104 & 0.208 mg/mouse /day) from 6 th up to 19 th day of gestation. The pregnant mice were killed by the cervical dislocation after 12 hrs from the last dose, the gravid uteri were dissected out, and foetuses were removed, weighted and examined for the live, dead and resorbed foetus numbers according to Cook & Farweather (1968) and Barlow et al (1980). A numbers of embryos from each pregnant mouse were placed in Bouins solution for a maximum of 2 days before assessment of external malformations and measuring of crown-rump length.…”

Section: Methodsmentioning

confidence: 99%

Fluoxetine Hcl Induced Intrauterine Foetal Growth Retardation And Skeletal Malformation In Pregnant Mice

Ali

Deen

Menshawy

et al. 2002

The Egyptian Journal of Hospital Medicine

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Fluoxetine is antidepressant drug which widely known as Prozac ® , is a fluorinated methyl phenoxy derivative of phenylpropylamine. Fluoxetine is a bicyclic antidepressant that differs structurally and pharmacologically from other currently available antidepressant agents. 80 pregnant mice were administrated oral doses of Fluoxetine (0.052, 0.104 & 0.208 mg/mouse /day) From 6 th up to both 15 th and 19 th days of gestation.The pregnant mice treated with Fluoxetine HCl showed states of instability, nervousness, twitching of head, agitation, hazy movement and marked reduction in food intake as well as reduction in the body weight. The results of uteri examination of pregnant mice groups on both 15 th and 19 th days of gestation showed remarkable reduction in their size, dismorphology, length and number of implantation sites as well as large reduction in the number of still live embryos.Increase in the number of dead and resorbed mouse embryos was dose dependant. Also, the results showed reduction in both body weight and crown rump of mouse embryos. The treated mouse foetuses showed several malformations as diminution in size, exenocephalia and skeletal malformations.

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Methods Used in Teratogenic Testing

Cited by 11 publications

References 6 publications

Vitamin C ameliorates fluoride-induced embryotoxicity in pregnant rats

Vitamin C ameliorates fluoride-induced embryotoxicity in pregnant rats

Comparative Genomics Identifies Putative Interspecies Mechanisms Underlying Crbn-Sall4-Linked Thalidomide Embryopathy

Fluoxetine Hcl Induced Intrauterine Foetal Growth Retardation And Skeletal Malformation In Pregnant Mice

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