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Natural disaster stress during pregnancy is linked to reprogramming of the placenta transcriptome in relation to anxiety and stress hormones in young offspring

Molecular Psychiatry volume 26, pages 6520–6530 (2021)Cite this article

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Abstract

Prenatal stress can lead to long-term adverse effects that increase the risk of anxiety and other emotional disorders in offspring. The in utero underpinnings contributing to such phenotypes remain unknown. We profiled the transcriptome of placental specimens from women who lived through Hurricane Sandy during pregnancy compared to those pregnant during non-Sandy conditions. Following birth, longitudinal assessments were conducted in their offspring during childhood (~3–4 years old) to measure steroid hormones (in hair) and behavioral and emotional problems. This revealed a significant link between prenatal Sandy stress (PNSS) and child HPA dysfunction, evident by altered cortisol, dehydroepiandrosterone (DHEA), and cortisol:DHEA levels. In addition, PNSS was associated with significantly increased anxiety and aggression. These findings coincided with significant reorganization of the placental transcriptome via vascular, immune, and endocrine gene pathways. Interestingly, many of the most prominently altered genes were known to be uniquely expressed in syncytiotrophoblast (STB)-subtype of placental cells and harbored glucocorticoid response elements in promoter regions. Finally, several vascular development- and immune-related placental gene sets were found to mediate the relationship between PNSS and childhood phenotypes. Overall, these findings suggest that natural disaster-related stress during pregnancy reprograms the placental molecular signature, potentially driving long-lasting changes in stress regulation and emotional health. Further examination of placental mechanisms may elucidate the environment’s contribution to subsequent risk for anxiety disorders later in life.

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Fig. 1: Prenatal Sandy stress (PNSS) is associated with robust differential gene expression across critical functional pathways in placenta.
Fig. 2: PNSS(+) is associated with reduced expression of trophoblast-subtype-specific genes and targets of glucocorticoid signaling.
Fig. 3: Placental genes related to immune activation and vascular development mediate the relationship between PNSS(+) and offspring HPA/neurobehavioral phenotypes.

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Data availability

The RNA-sequencing datasets generated and analyzed in the current study were submitted to the NCBI Sequencing Read Archive with accession code: PRJNA719417.

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Acknowledgements

We sincerely thank the mothers and their children who have participated in this project. This work was supported by grants MH102729 from the National Institute of Mental Health (NIMH) to YN and DA030359 from the National Institutes of Drug Abuse (NIDA) to YLH, along with ES029212 from the National Institute of Environmental Health Sciences (NIEHS) and HD067611 from the Eunice Kennedy Shriver National Institute of Child Health and Human Development (NICHD) to JC.

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  1. These authors contributed equally: Yoko Nomura, Gregory Rompala

Authors and Affiliations

  1. Department of Psychology, Queens College, CUNY, Flushing, New York, United States

    Yoko Nomura & Lexi Pritchett

  2. Department of Psychology, The Graduate Center, CUNY, Graduate School of Public Health, New York, NY, USA

    Yoko Nomura & Lexi Pritchett

  3. Department of Psychiatry and Neuroscience, Icahn School of Medicine at Mount Sinai, Addiction Institute of Mount Sinai, New York, NY, USA

    Yoko Nomura, Gregory Rompala & Yasmin L. Hurd

  4. Department of Environmental Medicine and Public Health, Icahn School of Medicine at Mount Sinai, New York, NY, USA

    Vasily Aushev & Jia Chen

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  1. Yoko Nomura
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Correspondence to Yasmin L. Hurd.

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Nomura, Y., Rompala, G., Pritchett, L. et al. Natural disaster stress during pregnancy is linked to reprogramming of the placenta transcriptome in relation to anxiety and stress hormones in young offspring. Mol Psychiatry 26, 6520–6530 (2021). https://doi.org/10.1038/s41380-021-01123-z

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