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Maternal diet disrupts the placenta-brain axis in a sex-specific manner

Publication ,  Journal Article
Ceasrine, AM; Devlin, BA; Bolton, JL; Green, LA; Jo, YC; Huynh, C; Patrick, B; Washington, K; Sanchez, CL; Joo, F; Brayan Campos-Salazar, A ...
November 13, 2021

High maternal weight is associated with a number of detrimental outcomes in offspring, including increased susceptibility to neurological disorders such as anxiety, depression, and communicative disorders (e.g. autism spectrum disorders). Despite widespread acknowledgement of sex-biases in the prevalence, incidence, and age of onset of these disorders, few studies have investigated potential sex-biased mechanisms underlying disorder susceptibility. Here, we use a mouse model to demonstrate how maternal high-fat diet, one contributor to overweight, causes endotoxin accumulation in fetal tissue, and subsequent perinatal inflammation influences sex-specific behavioral outcomes in offspring. In male high-fat diet offspring, increased macrophage toll like receptor 4 signaling results in excess 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 fetal brain, placenta, and maternal decidua 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, we find that fetal brain serotonin levels decrease as maternal dietary fat intake increases in males only. These findings uncover a microglia-dependent mechanism through which maternal diet may impact offspring susceptibility for neuropsychiatric disorder development in a sex-specific manner.

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November 13, 2021
 

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Ceasrine, A. M., Devlin, B. A., Bolton, J. L., Green, L. A., Jo, Y. C., Huynh, C., … Bilbo, S. D. (2021). Maternal diet disrupts the placenta-brain axis in a sex-specific manner. https://doi.org/10.1101/2021.11.12.468408
Ceasrine, Alexis M., Benjamin A. Devlin, Jessica L. Bolton, Lauren A. Green, Young Chan Jo, Carolyn Huynh, Bailey Patrick, et al. “Maternal diet disrupts the placenta-brain axis in a sex-specific manner,” November 13, 2021. https://doi.org/10.1101/2021.11.12.468408.
Ceasrine AM, Devlin BA, Bolton JL, Green LA, Jo YC, Huynh C, et al. Maternal diet disrupts the placenta-brain axis in a sex-specific manner. 2021 Nov 13;
Ceasrine, Alexis M., et al. Maternal diet disrupts the placenta-brain axis in a sex-specific manner. Nov. 2021. Crossref, doi:10.1101/2021.11.12.468408.
Ceasrine AM, Devlin BA, Bolton JL, Green LA, Jo YC, Huynh C, Patrick B, Washington K, Sanchez CL, Joo F, Brayan Campos-Salazar A, Lockshin ER, Kuhn C, Murphy SK, Simmons LA, Bilbo SD. Maternal diet disrupts the placenta-brain axis in a sex-specific manner. 2021 Nov 13;

DOI

Publication Date

November 13, 2021