Epigenetic effects of endogenous and exogenous glucocorticosteroids during pregnancy on the offspring: a systematic-narrative review.

Abstract

Backround: Τhe epigenetic effects of glucocorticosteroids-also known as glucocorticoids-(GCs) on the human epigenome are under constant in-depth examination. During uncomplicated pregnancy, endogenous GCs are normally increased, this increase being increased in stressful maternal conditions, such GC excess potentially having a deleterious effect on the fetus. In addition, however, synthetic GCs have long been used during pregnancy, not only for lung maturation in pregnancies at risk for preterm birth but also therapeutically for a large number of maternal diseases. Although GCs can be administrated as treatment during pregnancy, exhaustive study of the genome as well as of the compound's epigenetic effects has called their use into question.

Objectives: To scrutinize the desirable and undesirable effects of endogenous and exogenous GCs during pregnancy specifically as concerns epigenetic effects in the offspring and their impact in later life.

Methods: A comprehensive literature research was conducted in the electronic databases Medline, Google Scholar, and Cochrane Library, using specific keywords, up until March 2024. Data were collected only from original research and studies were included when endogenous GCs were measured or exogenous GCs were administered during pregnancy and their association with specific epigenetic changes, phenotypic, and biologic results, were recorded in the offspring.

Results: Twenty-three eligible cohort studies were collected among a total of 2692 papers. Eighteen studies with experimental animals and five human studies were included according to the inclusion criteria. One study with experimental animals along with two human studies involved endogenous GCs. Sixteen studies with experimental animals and two human studies involved GCs administered exogenously. All studies reported different epigenetic effects that resulted in phenotypic and biologic alterations. Many of them lasted into adult life.

Conclusions: Data from the reviewed studies indicate that excessive levels of GCs during pregnancy negatively affect the fetal epigenome resulting in an adverse impact on fetal health. Genes involving the HPA axis, DNA methylation per se, neurodevelopment, the immune system, and genes with tissue specific actions are affected. Caution and careful evaluation in the use of GCs during pregnancy are therefore warranted. Larger prospective studies of longer duration should be conducted based on the preliminary results of the present systematic-narrative review.