Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress.
Maternal DHA supplementation influences sex-specific disruption of placental gene expression following early prenatal stress.
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DOI：
10.1186/s13293-020-00356-x
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发表时间：
2021-01-09
影响因子：
7.9
通讯作者：
Beversdorf DQ
中科院分区：
文献类型：
--
作者：
Jašarević E;Hecht PM;Fritsche KL;Geary DC;Rivera RM;Beversdorf DQ
早期生活逆境被广泛认为是早期发育障碍的一个关键风险因素，并有助于成年后神经精神障碍的表现。神经发育障碍表现出强烈的性别偏见的易感性，介绍，发病和严重程度，虽然潜在的机制赋予脆弱性还没有得到很好的理解。怀孕期间的环境干扰，如营养不良或压力，与性别特异性重编程有关，导致成年后疾病风险增加，压力和营养不足可能是累加的，进一步加剧了后代的不良结局。为了确定母体补充二十二碳六烯酸（DHA）是否对暴露于早期产前应激（EPS）后的后代结果产生影响，给母鼠喂食纯化的10：1 ω-6/ω-3饮食，该饮食补充有1.0%预形成的DHA/kg饲料重量（富含DHA）或不补充额外的DHA（表示为对照饮食，CTL）。母鼠在妊娠第一周（胚胎日，E0.5-7.5）接受慢性可变应激，并在E12.5评估发育里程碑。暴露于早期产前应激（EPS）降低胎盘和胚胎重量的男性，但不是女性，暴露于CTL饮食。DHA富集逆转了EPS后胎盘和胚胎重量的性别特异性下降。在暴露于EPS的CTL饮食雄性的胎盘中，早期产前暴露上调了与氧和营养转运相关的基因的表达，包括缺氧诱导因子3α（HIF 3 α）、过氧化物酶体增殖物激活受体α（PPARα）和胰岛素样生长结合因子1（IGFBP 1）。在暴露于EPS的动物中，DHA的富集消除了雄性特异性的PPARα、HIF 3 α和IGFBP 1的上调。综上所述，这些研究表明，母体膳食DHA富集可能会缓冲母体在早期发育过程中对性别特异性结果的压力编程。
Early life adversity is widely recognized as a key risk factor for early developmental perturbations and contributes to the presentation of neuropsychiatric disorders in adulthood. Neurodevelopmental disorders exhibit a strong sex bias in susceptibility, presentation, onset, and severity, although the underlying mechanisms conferring vulnerability are not well understood. Environmental perturbations during pregnancy, such as malnutrition or stress, have been associated with sex-specific reprogramming that contribute to increased disease risk in adulthood, whereby stress and nutritional insufficiency may be additive and further exacerbate poor offspring outcomes. To determine whether maternal supplementation of docosahexanoic acid (DHA) exerts an effect on offspring outcome following exposure to early prenatal stress (EPS), dams were fed a purified 10:1 omega-6/omega-3 diet supplemented with either 1.0% preformed DHA/kg feed weight (DHA-enriched) or no additional DHA (denoted as the control diet, CTL). Dams were administered chronic variable stress during the first week of pregnancy (embryonic day, E0.5–7.5), and developmental milestones were assessed at E 12.5. Exposure to early prenatal stress (EPS) decreased placenta and embryo weight in males, but not females, exposed to the CTL diet. DHA enrichment reversed the sex-specific decrease in placenta and embryo weight following EPS. Early prenatal exposure upregulated expression of genes associated with oxygen and nutrient transport, including hypoxia inducible factor 3α (HIF3α), peroxisome proliferator-activated receptor alpha (PPARα), and insulin-like growth binding factor 1 (IGFBP1), in the placenta of CTL diet males exposed to EPS. DHA enrichment in EPS-exposed animals abrogated the male-specific upregulation of PPARα, HIF3α, and IGFBP1. Taken together, these studies suggest that maternal dietary DHA enrichment may buffer against maternal stress programming of sex-specific outcomes during early development.
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影响因子：
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作者：
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作者：
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通讯作者：
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DOI：
10.1073/pnas.1300065110
发表时间：
2013-03-26
影响因子：
11.1
作者：
Howerton, Christopher L.;Morgan, Christopher P.;Bale, Tracy L.
通讯作者：
Bale, Tracy L.