How is prenatal stress transmitted from the mother to the fetus?

Prenatal stress programmes long-lasting neuroendocrine and behavioural changes in the offspring. Often this programming is maladaptive and sex specific. For example, using a rat model of maternal social stress in late pregnancy, we have demonstrated that adult prenatally stressed male, but not prenatally stressed female offspring display heightened anxiety-like behaviour, whereas both sexes show hyperactive hypothalamo-pituitary-adrenal (HPA) axis responses to stress. Here, we review the current knowledge of the mechanisms underpinning dysregulated HPA axis responses, including evidence supporting a role for reduced neurosteroid-mediated GABAergic inhibitory signalling in the brains of prenatally stressed offspring. How maternal psychosocial stress is signalled from the mother to the fetuses is unclear. Direct transfer of maternal glucocorticoids to the fetuses is often considered to mediate the programming effects of maternal stress on the offspring. However, protective mechanisms including attenuated maternal stress responses and placental 11β-hydroxysteroid dehydrogenase-2 (which inactivates glucocorticoids) should limit materno-fetal glucocorticoid transfer during pregnancy. Moreover, a lack of correlation between maternal stress, circulating maternal glucocorticoid levels and circulating fetal glucocorticoid levels is reported in several studies and across different species. Therefore, here we interrogate the evidence for a role for maternal glucocorticoids in mediating the effects of maternal stress on the offspring and consider the evidence for alternative mechanisms, including an indirect role for glucocorticoids and the contribution of changes in the placenta in signalling the stress status of the mother to the fetus. © 2024. Published by The Company of Biologists Ltd.

Citation

Ying Sze, Paula J Brunton. How is prenatal stress transmitted from the mother to the fetus? The Journal of experimental biology. 2024 Mar 07;227(Suppl_1)

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PMID: 38449331

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