Maki Yohei, Nygard Karen, Hammond Robert R, Regnault Timothy R H, Richardson Bryan S
Department of Obstetrics and Gynecology, University of Western Ontario, London, Ontario, Canada.
Department of Physiology and Pharmacology, University of Western Ontario, London, Ontario, Canada.
Dev Neurosci. 2019;41(5-6):290-299. doi: 10.1159/000506939. Epub 2020 Apr 21.
We determined whether maternal nutrient restriction (MNR) in guinea pigs leading to fetal growth restriction (FGR) impacts markers for brain hypoxia and oxidative stress.
Guinea pigs were fed ad libitum (control) or 70% of the control diet before pregnancy, switching to 90% at mid-pregnancy (MNR). Near term, hypoxyprobe-1 (HP-1) was injected into pregnant sows. Fetuses were then necropsied and brain tissues were processed for HP-1 (hypoxia marker) and 4HNE, 8-OHdG, and 3-nitrotyrosine (oxidative stress markers) immunoreactivity (IR).
FGR-MNR fetal and brain weights were decreased 38 and 12%, respectively, with brain/fetal weights thereby increased 45% as a measure of brain sparing, and more so in males than females. FGR-MNR HP-1 IR was increased in most of the brain regions studied, and more so in males than females, while 4HNE and 8-OHdG IR were increased in select brain regions, but with no sex differences.
Chronic hypoxia is likely to be an important signaling mechanism in the FGR brain, but with males showing more hypoxia than females. This may involve sex differences in adaptive decreases in growth and normalizing of oxygen, with implications for sex-specific alterations in brain development and risk for later neuropsychiatric disorder.
我们确定了豚鼠孕期母体营养限制（MNR）导致胎儿生长受限（FGR）是否会影响脑缺氧和氧化应激标志物。
豚鼠在怀孕前自由采食（对照组）或给予对照组70%的饮食，在孕期中期改为90%（MNR组）。临近足月时，将低氧探针-1（HP-1）注入怀孕母猪体内。然后对胎儿进行尸检，并对脑组织进行处理，以检测HP-1（缺氧标志物）以及4-羟基壬烯醛（4HNE）、8-羟基脱氧鸟苷（8-OHdG）和3-硝基酪氨酸（氧化应激标志物）的免疫反应性（IR）。
FGR-MNR组胎儿体重和脑重分别下降了38%和12%，脑重/胎儿体重增加了45%，作为脑保护的一种衡量指标，雄性比雌性增加得更多。FGR-MNR组在大多数研究的脑区中HP-1 IR增加，雄性比雌性增加得更多，而4HNE和8-OHdG IR在特定脑区增加，但无性别差异。
慢性缺氧可能是FGR脑内的一种重要信号机制，但雄性比雌性表现出更多的缺氧。这可能涉及生长适应性降低和氧正常化方面的性别差异，对脑发育中的性别特异性改变以及后期神经精神疾病风险具有影响。
