Folic acid supplementation of pregnant mice suppresses heat-induced neural tube defects in the offspring

Folic acid supplementation of pregnant mice suppresses heat-induced neural tube defects in the offspring
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DOI:
10.1093/jn/129.11.2070
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发表时间:
1999-11-01
影响因子:
4.2
通讯作者:
Shiota, K
Shiota, K
中科院分区:
医学2区
文献类型:
--
作者:
Shin, JH;Shiota, K

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神经管缺陷(NTD)是一组由胚胎发育早期神经管未能闭合引起的畸形,是人类最常见的先天性畸形之一。据报道,在怀孕前和怀孕的头几个月内,通过补充叶酸(FA)可以预防人体中相当大比例的NTD,并且肌醇(MI)被证明可以降低FA不能预防的曲尾小鼠中NTD的发生率。妊娠早期短暂的母体高热(HT)与人类和实验动物的NTD有关,当妊娠小鼠暴露于HT时,经常诱发前部NTD,包括露脑和无脑畸形。我们研究了孕鼠补充FA或MI对后代热诱导NTD发生的影响。当孕鼠从妊娠第0.5天至第9.5天每天给予FA(3 mg/kg)并在第8.5天加热时,胎儿NTD的患病率(26.6%)显著低于HT组(38.6%; P < 0.05)。然而,我们未能检测到MI(500 mg/kg)的预防作用。这项研究的结果表明,产前补充FA降低MT诱导的NTD小鼠和足够的FA摄入量在怀孕早期,可建议避免出生畸形儿。
Neural tube defects (NTD) are a group of malformations that result from the failure of the neural tube to close early in embryonic development and among the mast common congenital malformations in humans. It has been reported that a substantial proportion of NTD in humans can be prevented by folic acid (FA) supplementation prior to conception and during the first months of pregnancy, and myo-inositol (MI) was shown to reduce the incidence of NTD in curly tail mice which are not prevented by FA. Brief maternal hyperthermia (HT) early in pregnancy has been implicated in NTD both in humans and laboratory animals, and anterior NTD including exencephaly and anencephaly are induced frequently when pregnant mice are exposed to HT. We examined the effect of FA or MI supplementation of pregnant mice on the occurrence of heat-induced NTD in the offspring. When pregnant mice were treated with FA (3 mg/kg) daily from gestational day (GD) 0.5 through GD 9.5 and heated at GD 8.5, the prevalence of NTD in the fetuses (26.6%) was significantly lower than the corresponding figure in the HT alone group (38.6%; P < 0.05). However we failed to detect the preventive effect of MI (500 mg/kg). The results of this study suggest that prenatal FA supplementation decreases MT-induced NTD in mice and sufficient FA intake during early pregnancy may be recommended to avoid the birth of malformed children.