Reduction in diabetes-induced craniofacial defects by maternal immune stimulation
Reduction in diabetes-induced craniofacial defects by maternal immune stimulation
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DOI：
10.1002/bdrb.20062
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发表时间：
2006-02-01
影响因子：
--
通讯作者：
Holladay, SD
中科院分区：
文献类型：
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作者：
Hrubec, TC;Prater, MR;Holladay, SD
背景技术背景：母体糖尿病可在实验室动物和人类中诱发许多发育异常，包括面部畸形和神经管闭合缺陷。糖尿病妇女的新生儿出生缺陷的发生率比非糖尿病妇女高约3-5倍。在小鼠中，母体免疫系统的非特异性激活可以减少由多种病因引起的胎儿异常，包括糖尿病诱导的神经管缺陷。本研究旨在确定非特异性母体免疫刺激是否也可以减少糖尿病引起的颅面缺陷。方法：在链脲佐菌素（STZ）处理之前，通过母体足垫注射弗氏完全佐剂（FCA）、母体腹膜内（i. p.）注射粒细胞-巨噬细胞集落刺激因子（GM-CSF），或母体腹膜内注射干扰素-γ（IFN γ）。链脲霉素（200 mg/kg i. p.）用于在繁殖前诱导雌性ICR小鼠的高血糖（26-35 mmol血糖）。在妊娠第17天采集每个给药组12-18窝胎仔。结果：在所有高血糖组的胎儿中均观察到颅面缺陷。用IFN γ或GM-CSE免疫刺激的母鼠的胎儿缺陷发生率显著降低。最常见的缺陷是上颌和下颌长度减少。这两种情况都是通过母体用GM-CSF刺激来预防的。结论：母体免疫刺激可降低糖尿病颅面胚胎病的发生率。这些保护作用的机制尚不清楚，但可能涉及母体或胎儿产生细胞因子或生长因子，保护胎儿免受高甘油血症的失调作用。出生缺陷研究（B部分）77：1-9，2006年。(c)2005 Wiley-Liss，Inc.
BACKGROUND: Maternal diabetes can induce a number of developmental abnormalities in laboratory animals and humans, including facial deformities and defects in neural tube closure. The incidence of birth defects in newborns of diabetic women is approximately 3-5 times higher than among non-diabetics. In mice, non-specific activation of the maternal immune system can reduce fetal abnormalities caused by diverse etiologies, including diabetes induced neural tube defects. This study was conducted to determine whether non-specific maternal immune stimulation could reduce diabetes-induced craniofacial defects as well. METHODS: Maternal immune function was stimulated before streptozocin (STZ) treatment by maternal footpad injection with Freund's complete adjuvant (FCA), maternal intraperitoneal (i.p.) injection with granulocyte-macrophage colony-stimulating factor (GM-CSF), or maternal i.p. injection with interferon-gamma (IFN gamma). Streptozocin (200 mg/kg i.p.) was used to induce hyperglycemia (26-35 mmol blood glucose) in female ICR mice before breeding. Fetuses from 12-18 litters per treatment group, were collected at Day 17 of gestation. RESULTS: Craniofacial defects were observed in fetuses from all hyperglycemic groups. The incidence of defects was significantly decreased in fetuses from dams immune stimulated with IFN gamma or GM-CSE The most common defects were reduced maxillary and mandibular lengths. Both were prevented by maternal stimulation with GM-CSF. CONCLUSION: Maternal immune stimulation reduced the incidence of diabetic craniofacial embryopathy. The mechanisms for these protective effects are unknown but may involve maternal or fetal production of cytokines or growth factors that protect the fetus from the dysregulatory effects of hyperglycernia. Birth Defects Res (Part B) 77:1-9, 2006. (c) 2005 Wiley-Liss, Inc.