Prenatal Introduction of Dexamethasone Causes Disruption of Glucocorticoid Feedback Associated with a Change in the Amount of Corticosteroid Receptors in Extrahypothalamic Brain Structures of Adult Rats

Abstract

As are other artificial glucocorticoids, dexamethasone is widely used in everyday obstetric practice. The threat of termination of pregnancy is an indication for the use of glucocorticoids. However, there is evidence that the introduction of glucocorticoids during pregnancy can lead to impaired brain development and behavior of offspring that can be caused by a change in the activity of the hypothalamic–pituitary–adrenocortical system (HPAS) due to past effects. The aim of the present work was to study the effect of the introduction of synthetic hormone dexamethasone at the 14th–16th (DM14–16) and 17th–19th (DM17–19) days of prenatal ontogenesis on the stress reactivity of the HPAS in adult 3-month-old rats, as well as on the level of gluco- (GR) and mineralocorticoid (MR) receptors in the most vulnerable areas of the brain (hippocampus and neocortex). Significant intergroup differences in the dynamics of a change in the level of corticosterone in the blood of adult rats in response to a weak stress effect (rapid stress reactivity test) were detected. Using the immunohistochemical method, changes in the expression (the amount of immunopositive cells) of GR and MR were studied in CA1 field and dentate gyrus (DG) of the hippocampus, as well as in second and fifth neocortex layers in adult male rats. In animals of the DM14–16 group, a significant decrease in the number of cells intensively stained using antibodies to GR in CA1 field, hippocampus DG, and neocortex layer V (to 24.5, 32.4, and 5.5%, respectively) as compared with the control were observed. The introduction of dexamethasone at the 17th–19th day of gestation also led to a decrease in the amount of intensively stained GR-immunopositive cells in the hippocampus CA1 field and neocortex layer V (to 31.9 and 35.7%, respectively), but to a lesser degree than in animals from the group DM14–16. A trend toward a decrease in the number of GR-positive cells is accompanied by an increase in immunoreactivity of the cells to MR. Thus, the introduction of dexamethasone at different periods of prenatal ontogenesis modifies the work of gluco- and mineralocorticoid receptors; however, the degree, localization, and direction of these changes differ depending on the time of the effect.

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Funding

This work was supported by the Russian Foundation for Basic Research, project no. 17-04-01118.

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Correspondence to E. I. Tyul’kova.

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Statement on the welfare of animals. All applicable international and national principles for the use of laboratory animals were followed. The protocols of the experiments were approved by the Commission on the Humane Treatment of Animals of Pavlov Institute of Physiology, Russian Academy of Sciences.

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Translated by A. Barkhash

Abbreviations: HPAS—hypothalamic–pituitary–adrenocortical system, GR—glucocorticoid receptor, DG—dentate gyrus, MR—mineralocorticoid receptor.

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Vetrovoi, O.V., Tyul’kova, E.I., Stratilov, V.A. et al. Prenatal Introduction of Dexamethasone Causes Disruption of Glucocorticoid Feedback Associated with a Change in the Amount of Corticosteroid Receptors in Extrahypothalamic Brain Structures of Adult Rats. Cell Tiss. Biol. 15, 24–33 (2021). https://doi.org/10.1134/S1990519X21010132

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Keywords:

  • prenatal development
  • brain
  • dexamethasone
  • hypothalamic–pituitary–adrenocortical system
  • gluco- and mineralocorticoid receptors