Maternal diet disrupts the placenta-brain axis in a sex-specific manner.
Maternal diet disrupts the placenta-brain axis in a sex-specific manner.
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母体饮食以性别特定方式破坏胎盘脑轴。
DOI：
10.1038/s42255-022-00693-8
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发表时间：
2022-12
影响因子：
20.8
通讯作者：
Bilbo, Staci D.
中科院分区：
文献类型：
--
作者：
Ceasrine, Alexis M.;Devlin, Benjamin A.;Bolton, Jessica L.;Green, Lauren A.;Jo, Young Chan;Huynh, Carolyn;Patrick, Bailey;Washington, Kamryn;Sanchez, Cristina L.;Joo, Faith;Campos-Salazar, A. Brayan;Lockshin, Elana R.;Kuhn, Cynthia;Murphy, Susan K.;Simmons, Leigh Ann;Bilbo, Staci D.
母亲体重过高与后代的不利后果有关，包括增加对神经疾病的易感性，如焦虑、抑郁和沟通障碍。尽管性别偏见在这些疾病的发展中得到了广泛的承认，但很少有研究调查潜在的性别偏见机制，这些机制可能是疾病易感性的基础。在这里，我们表明，母体高脂饮食(MHFD)会导致胎儿组织中内毒素的积累，随后的围产期炎症会导致后代的性别行为结果。在雄性mHFD后代中，巨噬细胞Toll样受体4信号的增加导致发育中的中缝背核中5-羟色胺神经元的小胶质细胞过度吞噬，降低了5-羟色胺在胎儿和成人脑中的生物利用度。对大量匹配的早孕人类样本进行批量测序，发现胎盘和脑组织中性别特异的转录组范围内的变化，以响应母亲甘油三酯的积累(饮食脂肪含量的替代指标)。此外，在雄性小鼠和男性人类样本中，随着胎盘甘油三酯的增加，胎儿大脑中的5-羟色胺水平降低。这些发现揭示了一种依赖小胶质细胞的机制，通过这种机制，母亲的饮食可以影响后代以性别特有的方式发展成神经精神障碍的易感性。
High maternal weight is associated with detrimental outcomes in offspring, including increased susceptibility to neurological disorders such as anxiety, depression, and communicative disorders. Despite widespread acknowledgement of sex-biases in the development of these disorders, few studies have investigated potential sex-biased mechanisms underlying disorder susceptibility. Here, we show that a maternal high-fat diet (mHFD) causes endotoxin accumulation in fetal tissue, and subsequent perinatal inflammation contributes to sex-specific behavioral outcomes in offspring. In male mHFD offspring, increased macrophage toll-like receptor 4 signaling results in excess microglial phagocytosis of serotonin neurons in the developing dorsal raphe nucleus, decreasing serotonin bioavailability in the fetal and adult brain. Bulk sequencing from a large cohort of matched first trimester human samples reveals sex-specific transcriptome-wide changes in placenta and brain tissue in response to maternal triglyceride accumulation (a proxy for dietary fat content). Further, fetal brain serotonin levels decrease as placental triglycerides increase in male mice and male human samples. These findings uncover a microglia-dependent mechanism through which maternal diet can impact offspring susceptibility for neuropsychiatric disorder development in a sex-specific manner.
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