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Prenatal stress effects on offspring brain and behavior: Mediators, alterations and dysregulated epigenetic mechanisms

Abstract

Prenatal environment significantly influences mammalian fetal development and adverse in utero conditions have life-long consequences for the offspring health. Research has revealed that a wide variety of prenatal stress factors lead to increased risk of vulnerability to neuropsychiatric disorders in the individuals. Multiple mediators are involved in stress transfer from mother to the developing fetus, with stress hormone cortisol being a chief player. Further, the developmental programming effects of prenatal stress have been observed in the form of alterations in the offspring brain at different levels. This review covers stress transfer mediators such as cortisol, serotonin, maternal cytokines, reactive oxygen species (ROS) and the maternal microbiota, and their role in fetal programming. Prenatal stress leads to alterations in the offspring brain at multiple levels, from molecular and cellular to structural. These alterations eventually result in lasting phenotypic alterations such as in the offspring behavior and cognition. Different brain alterations induced by prenatal stress such as in neural pruning processes, neural circuit formation, brain structural connectivity and epigenetic systems regulating neural gene expression are under focus in the second part of the review. The latter constitutes a key molecular mechanism involved in prenatal stress effects and has been discussed in more detail.

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Acknowledgements

AK thanks Council of Scientific and Industrial Research (CSIR 12th FYP Project UNDO-BSC0103) and Department of Biotechnology, India (BT/PR4014/MED/30/673/2011). SUH acknowledges UGC for Junior and Senior Research Fellowship. UAB acknowledges CSIR fellowship supports for doctoral research and department of Biotechnology, India, for senior research fellowship.

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Correspondence to Arvind Kumar.

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Corresponding editor: Neeraj Jain

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Haq, S.U., Bhat, U.A. & Kumar, A. Prenatal stress effects on offspring brain and behavior: Mediators, alterations and dysregulated epigenetic mechanisms. J Biosci 46, 34 (2021). https://doi.org/10.1007/s12038-021-00153-7

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Keywords

  • in utero stress
  • fetal neural programming
  • remodeled circuitry
  • affective disorder
  • cognitive disorder
  • epigenetic regulation