Abstract
Introduction: Periconceptional supplementation with multivitamins containing folic acid reduces the risk of congenital malformations. We have previously investigated the effect on the murine development of a multiple retinoic acid competitive antagonist, Bristol-Myers-Squibb 189453, showing that treated fetuses were affected with heart defects, thymus aplasia or hypoplasia, and severe anomalies of the central nervous system. Hereby, we analyzed the effects of nutritive therapy involving folic acid and methionine on teratogen-induced congenital defects in mice. Materials and methods: A total of 132 outbred CD1 litters were studied. Pregnant mice were divided into four experimental groups, and an oral supplementation of H2O or folic acid, or methionine, or folic acid+methionine was administered from 0.5 days postcoitum until the end of pregnancy. At 7.5 days postcoitum, mice from all these groups were administered Bristol-Myers-Squibb 189453 to induce the teratogenic effect. At the end of pregnancy, fetuses were dissected and tissues were analyzed by histology and flow cytometric assays. Results: Folic acid reduces congenital heart diseases from 81.3% to 64.8%, neural tube defects from 20.3% to 3.7%, and thymus abnormalities from 98.4% to 27.8%, restoring a normal number of differentiated thymus cells. Methionine is less effective in contrasting congenital heart diseases and neural tube defects, and induces thymus cell proliferation but not differentiation. Folic acid+methionine weakly reduce congenital heart diseases and neural tube defects, but consistently reduce the incidence of fetuses affected with thymus pathologies from 98.4% to 67.7%. Conclusions: Our results suggest that folic acid and methionine periconceptional supplementations may influence the incidence of congenital defects and may probably induce negative selection of embryos presenting developmental anomalies.
| Original language | English |
|---|---|
| Pages (from-to) | 100-109 |
| Number of pages | 10 |
| Journal | Cardiovascular Pathology |
| Volume | 18 |
| Issue number | 2 |
| DOIs | |
| Publication status | Published - Mar 2009 |
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Keywords
- BMS-189453
- Congenital anomalies
- Folic acid
- Methionine
- Retinoic acid
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine
- Pathology and Forensic Medicine
Cite this
Folic acid and methionine in the prevention of teratogen-induced congenital defects in mice. / Cipollone, Daria; Carsetti, Rita; Tagliani, Angela; Rosado, Maria Manuela; Borgiani, Paola; Novelli, Giuseppe; D'Amati, Giulia; Fumagalli, Lorenzo; Marino, Bruno; Businaro, Rita.
In: Cardiovascular Pathology, Vol. 18, No. 2, 03.2009, p. 100-109.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Folic acid and methionine in the prevention of teratogen-induced congenital defects in mice
AU - Cipollone, Daria
AU - Carsetti, Rita
AU - Tagliani, Angela
AU - Rosado, Maria Manuela
AU - Borgiani, Paola
AU - Novelli, Giuseppe
AU - D'Amati, Giulia
AU - Fumagalli, Lorenzo
AU - Marino, Bruno
AU - Businaro, Rita
PY - 2009/3
Y1 - 2009/3
N2 - Introduction: Periconceptional supplementation with multivitamins containing folic acid reduces the risk of congenital malformations. We have previously investigated the effect on the murine development of a multiple retinoic acid competitive antagonist, Bristol-Myers-Squibb 189453, showing that treated fetuses were affected with heart defects, thymus aplasia or hypoplasia, and severe anomalies of the central nervous system. Hereby, we analyzed the effects of nutritive therapy involving folic acid and methionine on teratogen-induced congenital defects in mice. Materials and methods: A total of 132 outbred CD1 litters were studied. Pregnant mice were divided into four experimental groups, and an oral supplementation of H2O or folic acid, or methionine, or folic acid+methionine was administered from 0.5 days postcoitum until the end of pregnancy. At 7.5 days postcoitum, mice from all these groups were administered Bristol-Myers-Squibb 189453 to induce the teratogenic effect. At the end of pregnancy, fetuses were dissected and tissues were analyzed by histology and flow cytometric assays. Results: Folic acid reduces congenital heart diseases from 81.3% to 64.8%, neural tube defects from 20.3% to 3.7%, and thymus abnormalities from 98.4% to 27.8%, restoring a normal number of differentiated thymus cells. Methionine is less effective in contrasting congenital heart diseases and neural tube defects, and induces thymus cell proliferation but not differentiation. Folic acid+methionine weakly reduce congenital heart diseases and neural tube defects, but consistently reduce the incidence of fetuses affected with thymus pathologies from 98.4% to 67.7%. Conclusions: Our results suggest that folic acid and methionine periconceptional supplementations may influence the incidence of congenital defects and may probably induce negative selection of embryos presenting developmental anomalies.
AB - Introduction: Periconceptional supplementation with multivitamins containing folic acid reduces the risk of congenital malformations. We have previously investigated the effect on the murine development of a multiple retinoic acid competitive antagonist, Bristol-Myers-Squibb 189453, showing that treated fetuses were affected with heart defects, thymus aplasia or hypoplasia, and severe anomalies of the central nervous system. Hereby, we analyzed the effects of nutritive therapy involving folic acid and methionine on teratogen-induced congenital defects in mice. Materials and methods: A total of 132 outbred CD1 litters were studied. Pregnant mice were divided into four experimental groups, and an oral supplementation of H2O or folic acid, or methionine, or folic acid+methionine was administered from 0.5 days postcoitum until the end of pregnancy. At 7.5 days postcoitum, mice from all these groups were administered Bristol-Myers-Squibb 189453 to induce the teratogenic effect. At the end of pregnancy, fetuses were dissected and tissues were analyzed by histology and flow cytometric assays. Results: Folic acid reduces congenital heart diseases from 81.3% to 64.8%, neural tube defects from 20.3% to 3.7%, and thymus abnormalities from 98.4% to 27.8%, restoring a normal number of differentiated thymus cells. Methionine is less effective in contrasting congenital heart diseases and neural tube defects, and induces thymus cell proliferation but not differentiation. Folic acid+methionine weakly reduce congenital heart diseases and neural tube defects, but consistently reduce the incidence of fetuses affected with thymus pathologies from 98.4% to 67.7%. Conclusions: Our results suggest that folic acid and methionine periconceptional supplementations may influence the incidence of congenital defects and may probably induce negative selection of embryos presenting developmental anomalies.
KW - BMS-189453
KW - Congenital anomalies
KW - Folic acid
KW - Methionine
KW - Retinoic acid
UR - http://www.scopus.com/inward/record.url?scp=61349100859&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=61349100859&partnerID=8YFLogxK
U2 - 10.1016/j.carpath.2008.02.007
DO - 10.1016/j.carpath.2008.02.007
M3 - Article
VL - 18
SP - 100
EP - 109
JO - Cardiovascular Pathology
JF - Cardiovascular Pathology
SN - 1054-8807
IS - 2
ER -