Sex differences in prenatal epigenetic programing of stress pathways

Abstract

Maternal stress experience is associated with neurodevelopmental disorders including schizophrenia and autism. Recent studies have examined mechanisms by which changes in the maternal milieu may be transmitted to the developing embryo and potentially translated into programing of the epigenome. Animal models of prenatal stress have identified important sex- and temporal-specific effects on offspring stress responsivity. As dysregulation of stress pathways is a common feature in most neuropsychiatric diseases, molecular and epigenetic analyses at the maternal–embryo interface, especially in the placenta, may provide unique insight into identifying much-needed predictive biomarkers. In addition, as most neurodevelopmental disorders present with a sex bias, examination of sex differences in the inheritance of phenotypic outcomes may pinpoint gene targets and specific windows of vulnerability in neurodevelopment, which have been disrupted. This review discusses the association and possible contributing mechanisms of prenatal stress in programing offspring stress pathway dysregulation and the importance of sex.

Keywords::

• Brain
• masculinization
• neurodevelopmental disorders
• placenta
• prenatal stress
• sex differences

Acknowledgments

The author would like to thank G. Dunn and C. Morgan for assistance with the manuscript. This work was supported by funds from NIH MH073030, MH087597, and MH091258.

Declaration of interest: The author reports no conflicts of interest. The author alone is responsible for the content and writing of the paper.