Maternal Undernutrition with Vaginal Inflammation Impairs the Neonatal Oligodendrogenesis in Mice

Abstract

Maternal undernutrition and infection during pregnancy may impair development of oligodendrocytes, thereby increasing risks of neuropsychiatric disorders of their children. We analyzed the effects of those risk factors on oligodendrogenesis in fetal and neonatal brains. Female mice were given low-protein or regular food for 2 weeks before their pregnancy. On the 14th day of pregnancy, they received a transvaginal injection of lipopolysaccharide to induce inflammation or control solution, consisting of four groups, depending on nutritional conditions with or without vaginal inflammation. We collected fetal brains on embryonic day (E) 17 for evaluating oligodendrocyte precursor cells (OPCs) and neonatal brains on postnatal day (P) 7 for evaluating mature oligodendrocytes. OPCs and mature oligodendrocytes were identified as positive immunostaining for oligodendrocyte-lineage transcription factor 2 and myelin basic protein, respectively. There was no difference in the number of OPCs in E17 brains among the four groups, suggesting that nutritional restriction with or without inflammation exerts no noticeable influence on the differentiation of OPCs. However, the number of mature oligodendrocytes was decreased in P7 brains obtained from nutrient-restricted mice with inflammation, suggesting that their combination impairs oligodendrogenesis in the neonatal brain. We also analyzed reactive astrocytes that express both glial fibrillary acidic protein and nestin for evaluating brain inflammation. The population of reactive astrocytes was increased in P7 brains derived from mice with LPS injection, irrespective of nutritional restriction, indicating that maternal vaginal inflammation induces neonatal brain inflammation. The maternal management of both nutrition and infection is crucial to prevent neuropsychiatric disorders of the children.

Maternal Undernutrition Induces the Expression of Hypoxia-Related Genes in the Fetal Brain

“…Seven-week-old virgin female C57BL/6N mice (bred at Clea Japan, Inc., Japan; kept the lights on12 hour cycle at 24°C) were divided into two groups; the mice in the L group were given low protein food (modified AIN-93G: Oriental Yeast Co., Ltd., Tokyo Japan) while the mice in the N group were given normal food (AIN-93G: Oriental Yeast Co., Ltd.). The low protein diet was designed as described in previous studies (Reeves et al 1993;Ito et al 2011a). In short, the low protein diet contained 48% protein of the normal food (low protein food: 8.67%, normal food: 17.90%).…”

Aberrant Expression of Hypoxia-Inducible Factor 1.ALPHA. in the Fetal Heart Is Associated with Maternal Undernutrition

“…Seven-week-old virgin female C57BL/6N mice (bred at Clea Japan, Inc., Japan; kept the lights on12 hour cycle at 24°C) were divided into two groups; the mice in L group were given low protein food (modified AIN-93G: Oriental Yeast Co., Ltd., Tokyo Japan) while the mice in N group were given normal food (AIN-93G: Oriental Yeast Co., Ltd.). The low protein food was referred to previous studies (Reeves et al 1993;Ito et al 2011). The low protein food contains 48% protein of normal food (protein content in low protein food: 8.67% and in normal food: 17.90%) and 94% calorie of the normal food (low protein food: 352.6 kcal/100 g and normal food: 377.0 kcal/100 g) (Ito et al 2011).…”

“…The low protein food was referred to previous studies (Reeves et al 1993;Ito et al 2011). The low protein food contains 48% protein of normal food (protein content in low protein food: 8.67% and in normal food: 17.90%) and 94% calorie of the normal food (low protein food: 352.6 kcal/100 g and normal food: 377.0 kcal/100 g) (Ito et al 2011). Water was given ad libitum from weaning.…”

Ultrasound Imaging of Mouse Fetal Intracranial Hemorrhage Due to Ischemia/Reperfusion

“…They were allowed free access to food and water ad libitum . The LP diet consisted of only 48% of the protein and 94% of the calorie contents of the N diet as suggested in previous studies (Reeves et al, 1993; Ito et al, 2011a,b). After a 2-week acclimatization period, the female mice were time mated and inspected for vaginal plugs the following morning.…”