TY - JOUR
T1 - A detailed characterization of congenital defects and mortality following moderate X-ray doses during neurulation
AU - Craenen, Kai
AU - Verslegers, Mieke
AU - Buset, Jasmine
AU - Baatout, Sarah
AU - Moons, L.
AU - Benotmane, Rafi
N1 - Score=10
PY - 2017/11/28
Y1 - 2017/11/28
N2 - Background: Both epidemiological and animal studies have previously indicated a
link between in utero radiation exposure and birth defects such as microphthalmos,
anophthalmos, and exencephaly. However, detailed knowledge on embryonic radiosensitivity
during different stages of neurulation is limited, especially in terms of
neural tube defect and eye defect development.
Methods: To assess the most radiosensitive stage during neurulation, pregnant
C57BL6/J mice were X-irradiated (0.5 Gy or 1.0 Gy) at embryonic days (E)7, E7.5,
E8, E8.5, or E9. Next, the fetuses were scored macroscopically for various defects
and prenatal resorptions/deaths were counted. In addition, cranial skeletal development
was ascertained using the alcian-alizarin method. Furthermore, postnatal/young
adult survival was followed until 5 weeks (W5) of age, after X-irradiation at E7.5
(0.1 Gy, 0.5 Gy, or 1.0 Gy). In addition, body and brain weights were registered at
adult age (W10) following X-ray exposure at E7.5 (0.1 Gy, 0.5 Gy).
Results: Several malformations, including microphthalmos and exencephaly, were
most evident after irradiation at E7.5, with significance starting respectively at 0.5 Gy
and 1.0 Gy. Prenatal mortality and weight were significantly affected in all irradiated
groups. Long-term follow-up of E7.5 irradiated animals revealed a reduction in survival
at 5 weeks of age after high dose exposure (1.0 Gy), while lower doses (0.5 Gy,
0.1 Gy) did not affect brain and body weight at postnatal week 10.
Conclusions: With this study, we gained more insight in radiosensitivity throughout
neurulation, and offered a better defined model to further study radiation-induced
malformations and the underlying mechanisms.
AB - Background: Both epidemiological and animal studies have previously indicated a
link between in utero radiation exposure and birth defects such as microphthalmos,
anophthalmos, and exencephaly. However, detailed knowledge on embryonic radiosensitivity
during different stages of neurulation is limited, especially in terms of
neural tube defect and eye defect development.
Methods: To assess the most radiosensitive stage during neurulation, pregnant
C57BL6/J mice were X-irradiated (0.5 Gy or 1.0 Gy) at embryonic days (E)7, E7.5,
E8, E8.5, or E9. Next, the fetuses were scored macroscopically for various defects
and prenatal resorptions/deaths were counted. In addition, cranial skeletal development
was ascertained using the alcian-alizarin method. Furthermore, postnatal/young
adult survival was followed until 5 weeks (W5) of age, after X-irradiation at E7.5
(0.1 Gy, 0.5 Gy, or 1.0 Gy). In addition, body and brain weights were registered at
adult age (W10) following X-ray exposure at E7.5 (0.1 Gy, 0.5 Gy).
Results: Several malformations, including microphthalmos and exencephaly, were
most evident after irradiation at E7.5, with significance starting respectively at 0.5 Gy
and 1.0 Gy. Prenatal mortality and weight were significantly affected in all irradiated
groups. Long-term follow-up of E7.5 irradiated animals revealed a reduction in survival
at 5 weeks of age after high dose exposure (1.0 Gy), while lower doses (0.5 Gy,
0.1 Gy) did not affect brain and body weight at postnatal week 10.
Conclusions: With this study, we gained more insight in radiosensitivity throughout
neurulation, and offered a better defined model to further study radiation-induced
malformations and the underlying mechanisms.
KW - eye defect
KW - neural tube defect
KW - radiation
KW - X-ray
KW - mortality
UR - http://ecm.sckcen.be/OTCS/llisapi.dll/open/27463170
U2 - 10.1002/bdr2.1161
DO - 10.1002/bdr2.1161
M3 - Article
SN - 2472-1727
SP - 1
EP - 16
JO - Birth Defects Research
JF - Birth Defects Research
ER -