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Isolating adverse effects of glucocorticoids on the embryonic cardiovascular system
Author(s) -
Teulings Noor E. W. D.,
Garrud Tessa A. C.,
Niu Youguo,
Skeffington Katie L.,
Beck Christian,
Itani Nozomi,
Conlon Fiona G.,
Botting Kimberley J.,
Nicholas Lisa M.,
Ashmore Thomas J.,
Blackmore Heather L.,
Tong Wen,
Camm Emily J.,
Derks Jan B.,
Logan Angela,
Murphy Michael P.,
Ozanne Susan E.,
Giussani Dino A.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.202000697r
Subject(s) - dexamethasone , glucocorticoid , offspring , embryo , ventricle , placenta , endocrinology , medicine , oxidative stress , biology , embryogenesis , fetus , adverse effect , andrology , pregnancy , microbiology and biotechnology , genetics
Antenatal glucocorticoid therapy reduces mortality in the preterm infant, but evidence suggests off‐target adverse effects on the developing cardiovascular system. Whether deleterious effects are direct on the offspring or secondary to alterations in uteroplacental physiology is unclear. Here, we isolated direct effects of glucocorticoids using the chicken embryo, a model system in which the effects on the developing heart and circulation of therapy can be investigated, independent of effects on the mother and/or the placenta. Fertilized chicken eggs were incubated and divided randomly into control (C) or dexamethasone (Dex) treatment at day 14 out of the 21‐day incubation period. Combining functional experiments at the isolated organ, cellular and molecular levels, embryos were then studied close to term. Chicken embryos exposed to dexamethasone were growth restricted and showed systolic and diastolic dysfunction, with an increase in cardiomyocyte volume but decreased cardiomyocyte nuclear density in the left ventricle. Underlying mechanisms included a premature switch from tissue accretion to differentiation, increased oxidative stress, and activated signaling of cellular senescence. These findings, therefore, demonstrate that dexamethasone treatment can have direct detrimental off‐target effects on the cardiovascular system in the developing embryo, which are independent of effects on the mother and/or placenta.