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Maternal diet disrupts the placenta–brain axis in a sex-specific manner
被引:0
作者:
Alexis M. Ceasrine
Benjamin A. Devlin
Jessica L. Bolton
Lauren A. Green
Young Chan Jo
Carolyn Huynh
Bailey Patrick
Kamryn Washington
Cristina L. Sanchez
Faith Joo
A. Brayan Campos-Salazar
Elana R. Lockshin
Cynthia Kuhn
Susan K. Murphy
Leigh Ann Simmons
Staci D. Bilbo
机构:
[1] Duke University,Department of Psychology and Neuroscience
[2] Georgia State University,Neuroscience Institute
[3] Duke University Medical Center,Department of Pharmacology and Cancer Biology
[4] Duke University Medical Center,Department of Neurobiology
[5] Duke University Medical Center,Department of Obstetrics and Gynecology
[6] University of California,Department of Human Ecology, Perinatal Origins of Disparities Center
[7] Davis,undefined
[8] Massachusetts General Hospital,undefined
来源:
Nature Metabolism
|
2022年
/
4卷
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D O I:
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学科分类号:
摘要:
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 causes endotoxin accumulation in fetal tissue, and subsequent perinatal inflammation contributes to sex-specific behavioural outcomes in offspring. In male offspring exposed to a maternal high-fat diet, increased macrophage Toll-like receptor 4 signalling results in excess microglial phagocytosis of serotonin (5-HT) neurons in the developing dorsal raphe nucleus, decreasing 5-HT bioavailability in the fetal and adult brains. Bulk sequencing from a large cohort of matched first-trimester human samples reveals sex-specific transcriptome-wide changes in placental and brain tissue in response to maternal triglyceride accumulation (a proxy for dietary fat content). Further, fetal brain 5-HT 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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页码:1732 / 1745
页数:13
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