Effects of the A y gene on susceptibility to hydrocortisone fetotoxicity and teratogenicity in mice

Self Cite

The effects of the Ay gene on the sensitive periods of hydrocortisone‐induced cleft palate and palatal slit were investigated in C57BL/6 (a/a) and its congenic strain of C57BL/6‐Ay (Ay/a) mice by using the single‐dose administration method. Matings were conducted as follows (femalex male): Group I, a/a × a/a; Group n, a/a ×Ay/a; and Group III, Ay/a × a/a. Pregnant females were subcutaneously given a single dose of 200 or 400 mg/kg of hydrocortisone on day 11, 12, 13 or 14 of pregnancy and killed on day 18 for examination of palatal defects of live fetuses. Cleft palate was produced in all groups by treatment on days 11–13 of pregnancy at a dose of 200 mg/kg without any increase in fetal mortality. In Group I, the maximum incidence was observed on day 11 and followed by a rapid decrease thereafter. In Group U, in which half of the fetuses were expected to carry the Ay gene, the incidence still remained high on day 12, although it was decreased to the level of Group I by day 13. In Group HI, in which maternal mice as well as half of their fetuses carried the Ay gene, significantly higher incidences were observed on days 12 and 13 with the maximum value on day 12 when compared with those in Groups I and/or II. Palatal slit was also induced in all groups on each of treatment days at a dose of 200 mg/kg. Although the incidences in both Groups I and II were high on days 11 and 12 and gradually decreased thereafter, the value on day 13 was significantly higher in Group II than in Group I. In Group IE, the maximum incidence was found on day 12 and the values on days 13 and 14 were still significantly higher than those in Groups I and/or II. These results indicate that the sensitive periods of hydrocortisone‐induced cleft palate and palatal slit are prolonged into the later stage of embryonic development as a result of the Ay‐gene effects.

Section: Discussionsupporting

confidence: 93%

Section: Resultssupporting

confidence: 66%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Effects of the Ay Gene on the Sensitive Periods of Hydrocortisone‐Induced Cleft Palate and Palatal Slit in Mice

Teramoto

1992

Self Cite

“…Since the reciprocal of the ED50 value in mgkg provides a measure of teratogenic potential, it is clear from the data given in Table 2, that triamcinolone acetonide is the most potent teratogen that induces palatal defect, followed by dexamethasone and prednisolone. Hydrocortisone (1 00 mg/kg/day) showed no potency of inducing palatal defects in rat fetuses, whereas three consecutive administrations of 50 mgkg hydrocortisone on days 10-13 of gestation in mice results in 44.2% (Teramoto et al, 1991) and 30 mgkg on day 11 of gestation results in 96% cleft palate in hamster (Shah and Kilistoff, 1976;Shah and Travill, 1976). The results in the present study also demonstrate that the synthetic glucocorticoids such as triamcinolone acetonide are much more potent teratogens than naturally occurring glucocorticoids like hydrocortisone.…”

Section: Resultsmentioning

confidence: 96%

Palatal Slit and Cleft Palate in Rats Treated with Glucocorticoids II. Comparative Teratogenicity of Prednisolone, Triamcinolone Acetonide and Hydrocortisone

Watanabe

Ishizuka

Nagao

1995

The induction of abnormal palatal development by three glucocorticoids; prednisolone, triamcinolone acetonide and hydrocortisone was evaluated in rat fetuses.Pregnant rats were injected subcutaneously with either prednisolone (12.5-100 mgkgl day), triamcinolone acetonide (0.25-2 mg/kg/day) or hydrocortisone (1 00 mg/kg/day) on days 14 and 15 of gestation. These females were humanely killed on day 20 of gestation and viable fetuses were inspected for their palatal abnormalities. The frequencies of cleft palate were significantly higher in the group treated with 100 mg/kg/day prednisolone (10.6%), and in the groups treated with 0.5, 1 and 2 mg/kg/day triamcinolone acetonide (8.6%, 26.1% and 58.3%, respectively) than the control frequency of 0%. Triamcinolone acetonide was 70 times as potent as prednisolone in inducing palatal slit, with ED50 value of 1 .O mgkg/day and 70 mgkg/day, respectively. Hydrocortisone showed no potentiality for the induction of cleft palate and palatal slit. Other developmental abnormalities including omphalocele and general edema, late resorption, and growth retardation were induced by triamcinolone acetonide and prednisolone. These findings indicate that triamcinolone acetonide has a significantly higher potentiality for the induction of palatal slit in rats, as well as in mice, compared to prednisolone and hydrocortisone.In a previous study (Ishizuka et al., 1993), it was reported that dexamethasone produces palatal slits with an appreciable frequency in rat fetuses, as well as in mouse fetuses. Palatal slit involved a failure of fusion of the premaxilla and palatal shelves, corresponding to stage 7 in normal palatal closure (Biddle, 1980). In normal development, the premaxilla fuses with the dorsal part of the palatal shelves, from the foremost to near the third ruga; palatal slit does not show such fusion and the oral cavity connected with the nasal cavity

“…Our previous experiments have demonstrated that the AY gene, a coat color gene of the mouse, is associated with susceptibility to teratogenicity of a 4-day dose of hydrocortisone as compared with the a gene (Teramoto et al, 1991). Single-dose administration experiments have revealed that not only is susceptibility to hydrocortisone-induced cleft palate enhanced by the AY-gene effects, but also the sensitive periods of this teratogenicity are shifted to the later stage of embryonic development (Hatakenaka and Teramoto, 1992).…”

mentioning

confidence: 99%

Delay in the Development of the Secondary Palate in Ay/a Mouse Embryos

Aoyama

Kaneda

Teramoto

1996

Self Cite

The effects of the AY gene on the normal development were investigated by using a inbred strain of C57BLi6 (ah) and its congenic strain of C57BU6-Ay (A%) mice.Three mating groups (female X male), i.e., group I, ala x ala; group 11, aia X Apia; and group 111, A% X aia, were set, and the rating of normal development was compared among the groups on gestation days 13, 14, 15 or 16 with special attention to the secondary palate. On day 13, the palates were wide-open and the palatal shelves were vertical in all embryos in all groups. In group I, both shelves became horizontal in 63.3% of the embryos on day 14. The incidences of embryos having completely closed palates were 95.8% and 100% on days 15 and 16, respectively. In group 11, in which half of the embryos were expected to carry the AY gene, the frequencies of shelf horizontalization on day 14 (31.1%) and of the complete closure on day 15 (74.3%) were significantly lowered as compared with those in group I, although the external morphological rating was comparable. On day 16, however, the palatal closure was completed in almost all embryos. In group 111, in which maternal mice as well as half of their embryos carried the AY gene, the external morphological rating was delayed as compared with that in either group I or 11, and the frequencies of shelf horizontalization on day 14 and of the complete closure on day 15 were as low as 10.9% and 39.6%, respectively. The palatal closure was not yet completed in 15.3% of the embryos on day 16. These results indicate that the AY gene causes a delay in shelf horizontalization and closure of the secondary palate of mouse embryos as compared with the a gene.