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Isolating adverse effects of glucocorticoids on the embryonic cardiovascular system

Noor E W D Teulings1, Tessa A C Garrud2, Youguo Niu2

  • 1Institute of Metabolic Science-Metabolic Research Laboratories, University of Cambridge, Addenbrooke's Hospital, Cambridge, UK.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
|June 6, 2020
PubMed

Insights

Antenatal glucocorticoid therapy, while reducing preterm infant mortality, can directly harm the developing cardiovascular system. This study shows dexamethasone exposure in chicken embryos causes heart dysfunction independent of maternal or placental effects.

Area of Science:

  • Developmental biology
  • Cardiovascular physiology
  • Pharmacology

Background:

  • Antenatal glucocorticoid therapy is crucial for preterm infant survival.
  • Concerns exist regarding potential cardiovascular side effects of this therapy.
  • The direct impact on the fetus versus maternal/placental alterations remains unclear.

Purpose of the Study:

  • To investigate the direct effects of glucocorticoids on the developing cardiovascular system.
  • To elucidate the mechanisms underlying these effects, independent of maternal or placental factors.
  • To utilize a validated animal model for studying antenatal drug impacts.

Main Methods:

  • Utilized chicken embryos as a model to isolate direct fetal drug effects.
  • Administered dexamethasone (Dex) to embryos during incubation.
  • Conducted functional, cellular, and molecular analyses of the embryonic heart and circulation.

Main Results:

  • Dexamethasone-exposed embryos exhibited growth restriction and cardiac dysfunction (systolic and diastolic).
  • Cardiomyocyte alterations included increased volume and decreased nuclear density in the left ventricle.
  • Mechanisms involved premature differentiation, oxidative stress, and cellular senescence activation.

Conclusions:

  • Dexamethasone has direct detrimental effects on the embryonic cardiovascular system.
  • These adverse effects are independent of maternal and placental physiology.
  • Findings highlight potential risks of antenatal glucocorticoid therapy on fetal heart development.
Keywords:
antenatal glucocorticoid therapycardiac functioncellular senescenceoxidative stress

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