Modulation of Embryo Sensitivity to Teratogen by Nonspecific Intrauterine Immunopotentiation

Torchinsky, Arkady; Fein, Amos; Toder, V.

doi:10.3109/15376519509045907

Cited by 23 publications

(21 citation statements)

References 15 publications

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“…Also, intrauterine injection of allogeneic paternal splenocytes enhanced the tolerance of F 1 embryos to chemical teratogens [10]. Similar results were obtained in ICR mice by intrauterine administration of xenogeneic rat splenocytes [11]. This fetal protection was accompanied by enhancement of uterine colony stimulating factor (CSF)-1 mRNA expression, suggesting a possible involvement of CSF-1 in this immunostimulationinduced protective effect [12].…”

Section: Introductionsupporting

confidence: 69%

A possible role for granulocyte macrophage-colony stimulating factor in modulating teratogen-induced effects

Savion

Brengauz-Breitmann

Torchinsky

et al. 1999

Teratog. Carcinog. Mutagen.

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It was already shown that stimulation of the maternal immune system by allogeneic or xenogeneic leukocytes is capable of affecting embryonic responses to teratogenic insults and various cytokines, including granulocyte macrophage‐colony stimulating factor (GM‐CSF), were implicated as mediators of this effect. Therefore, in the present study we tried to assess the ability of GM‐CSF to modulate teratogenic activity, along with possible changes in systemic as well as local maternal immune responses, that might be involved in the process. Thus, the percentage of cyclophosphamide (CP)‐treated embryos exhibiting limb malformations was shown to decrease significantly following GM‐CSF administration. This effect was found to be comparable to that demonstrated by intrauterine leukocytes administration. GM‐CSF treatment resulted in a significant enhancement in maternal splenocytes Con‐A‐induced proliferation, as well as Interleukin‐2 (IL‐2) and IL‐3 production. Examination of leukocyte cell surface antigens expressed by splenocytes revealed no statistically‐significant changes in the level of the T lymphoid antigens Thy‐1, CD5, CD4, CD8 and CD3, the macrophage antigen Mac‐1, and the adhesion molecules LFA‐1α, LFA‐1β and L‐Selectin, following GM‐CSF immunostimulation. In parallel, immunohistochemical analysis of the uteroplacental unit revealed Mac‐1 and to a lesser extent LFA‐1β‐positive cells localized to the myometrium and the placenta in both the control and the GM‐CSF‐treated groups, while no cells expressing Thy‐1, CD3, CD4, CD8, or LFA‐1α could be demonstrated. Our results suggest a possible role for GM‐CSF in modulating teratogen‐induced effects, a process in which maternal immune responses such as splenocytes proliferation and cytokine production might be involved. Teratogenesis Carcinog. Mutagen. 19:171–182, 1999. © 1999 Wiley‐Liss, Inc.

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Section: Introductionsupporting

confidence: 69%

A possible role for granulocyte macrophage-colony stimulating factor in modulating teratogen-induced effects

Savion

Brengauz-Breitmann

Torchinsky

et al. 1999

Teratog. Carcinog. Mutagen.

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“…at 8:00 AM on day 12 of pregnancy at a dose of 40 mg/kg (in 0.5 ml saline per 20 g body weight). The results of previous studies [3,4,13] indicated that this dose of CP will affect all tested embryonic organs in all embryos.…”

Section: Materials and Methods Animal Modelmentioning

confidence: 98%

“…Our earlier studies [3] revealed that in litters of mice treated with doses of 15-20 mg/kg CP, the incidence of fetuses with limb reduction anomalies was higher than that of fetuses with craniofacial anomalies (e.g., micrognathia, open eyes, cleft palate, exencephaly) and only embryos having digit anomalies were observed in mice treated with 10 mg/kg CP. These data suggested that the limb is more sensitive than the head to a CP-induced teratogenic insult.…”

Section: Discussionmentioning

confidence: 99%

“…We have shown that in litters of mice treated with a dose of 40 mg/kg of cyclophosphamide (CP) and tested on day 19 of pregnancy, all fetuses had craniofacial (agnathia, exencephaly, cleft palate, open eyes), limb reduction anomalies (amelia or phocomelia), and severe growth retardation [3]. In parallel, it has been observed [4] that this dose of CP initiates apoptosis in the limbs, head, and liver of murine embryos 24 h after CP administration and that limb reduction and craniofacial anomalies are clearly seen by 48 h after CP treatment.…”

Section: Introductionmentioning

confidence: 99%

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Cellular events and the pattern of p53 protein expression following cyclophosphamide-initiated cell death in various organs of developing embryo

Torchinsky

Ivnitsky

Savion

et al. 1999

Teratog. Carcinog. Mutagen.

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“…Intrauterine administration of rat splenocytes was carried out 3 weeks before mating as described previously [13]. Briefly, spleens from Long -Evans male rats were teased mechanically into single cell suspensions.…”

Section: Immunopotentiationmentioning

confidence: 99%

Diabetes teratogenicity is accompanied by alterations in macrophages and T cell subpopulations in the uterus and lymphoid organs

Savion

Gidon-Dabush

Fein

et al. 2004

International Immunopharmacology

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Modulation of Embryo Sensitivity to Teratogen by Nonspecific Intrauterine Immunopotentiation

Cited by 23 publications

References 15 publications

A possible role for granulocyte macrophage-colony stimulating factor in modulating teratogen-induced effects

A possible role for granulocyte macrophage-colony stimulating factor in modulating teratogen-induced effects

Cellular events and the pattern of p53 protein expression following cyclophosphamide-initiated cell death in various organs of developing embryo

Diabetes teratogenicity is accompanied by alterations in macrophages and T cell subpopulations in the uterus and lymphoid organs

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