Effect of maternal steroid on developing diaphragm integrity.
Antenatal steroids reduce the severity of initial respiratory distress of premature newborn babies but may have an adverse impact on other body organs. The study aimed to examine the effect of maternal steroids on postnatal respiratory muscle function during development and elucidate the mechanisms...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Public Library of Science (PLoS)
2014-01-01
|
| Series: | PLoS ONE |
| Online Access: | http://europepmc.org/articles/PMC3969349?pdf=render |
| _version_ | 1818387352684331008 |
|---|---|
| author | Yong Song Denise L Demmer Gavin J Pinniger Tina Lavin Mia V MacMillan Jane J Pillow Anthony J Bakker |
| author_facet | Yong Song Denise L Demmer Gavin J Pinniger Tina Lavin Mia V MacMillan Jane J Pillow Anthony J Bakker |
| author_sort | Yong Song |
| collection | DOAJ |
| description | Antenatal steroids reduce the severity of initial respiratory distress of premature newborn babies but may have an adverse impact on other body organs. The study aimed to examine the effect of maternal steroids on postnatal respiratory muscle function during development and elucidate the mechanisms underlying the potential myopathy in newborn rats. Pregnant rats were treated with intramuscular injections of 0.5 mg/kg betamethasone 7 d and 3 d before birth. Newborn diaphragms were dissected for assessment of contractile function at 2 d, 7 d or 21 d postnatal age (PNA), compared with age-matched controls. The expression of myosin heavy chain (MHC) isoforms and atrophy-related genes and activity of intracellular molecular signalling were measured using quantitative PCR and/or Western blot. With advancing PNA, neonatal MHC gene expression decreased progressively while MHC IIb and IIx isoforms increased. Protein metabolic signalling showed high baseline activity at 2 d PNA, and significantly declined at 7 d and 21 d. Antenatal administration of betamethasone significantly decreased diaphragm force production, fatigue resistance, total fast fibre content and anabolic signalling activity (Akt and 4E-BP1) in 21 d diaphragm. These responses were not observed in 2 d or 7 d postnatal diaphragm. Results demonstrate that maternal betamethasone treatment causes postnatal diaphragmatic dysfunction at 21 d PNA, which is attributed to MHC II protein loss and impairment of the anabolic signalling pathway. Developmental modifications in MHC fibre composition and protein signalling account for the age-specific diaphragm dysfunction. |
| first_indexed | 2024-12-14T04:08:35Z |
| format | Article |
| id | doaj.art-01468b33e7e94645bed3d639d6aa7072 |
| institution | Directory Open Access Journal |
| issn | 1932-6203 |
| language | English |
| last_indexed | 2024-12-14T04:08:35Z |
| publishDate | 2014-01-01 |
| publisher | Public Library of Science (PLoS) |
| record_format | Article |
| series | PLoS ONE |
| spelling | doaj.art-01468b33e7e94645bed3d639d6aa70722022-12-21T23:17:44ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9322410.1371/journal.pone.0093224Effect of maternal steroid on developing diaphragm integrity.Yong SongDenise L DemmerGavin J PinnigerTina LavinMia V MacMillanJane J PillowAnthony J BakkerAntenatal steroids reduce the severity of initial respiratory distress of premature newborn babies but may have an adverse impact on other body organs. The study aimed to examine the effect of maternal steroids on postnatal respiratory muscle function during development and elucidate the mechanisms underlying the potential myopathy in newborn rats. Pregnant rats were treated with intramuscular injections of 0.5 mg/kg betamethasone 7 d and 3 d before birth. Newborn diaphragms were dissected for assessment of contractile function at 2 d, 7 d or 21 d postnatal age (PNA), compared with age-matched controls. The expression of myosin heavy chain (MHC) isoforms and atrophy-related genes and activity of intracellular molecular signalling were measured using quantitative PCR and/or Western blot. With advancing PNA, neonatal MHC gene expression decreased progressively while MHC IIb and IIx isoforms increased. Protein metabolic signalling showed high baseline activity at 2 d PNA, and significantly declined at 7 d and 21 d. Antenatal administration of betamethasone significantly decreased diaphragm force production, fatigue resistance, total fast fibre content and anabolic signalling activity (Akt and 4E-BP1) in 21 d diaphragm. These responses were not observed in 2 d or 7 d postnatal diaphragm. Results demonstrate that maternal betamethasone treatment causes postnatal diaphragmatic dysfunction at 21 d PNA, which is attributed to MHC II protein loss and impairment of the anabolic signalling pathway. Developmental modifications in MHC fibre composition and protein signalling account for the age-specific diaphragm dysfunction.http://europepmc.org/articles/PMC3969349?pdf=render |
| spellingShingle | Yong Song Denise L Demmer Gavin J Pinniger Tina Lavin Mia V MacMillan Jane J Pillow Anthony J Bakker Effect of maternal steroid on developing diaphragm integrity. PLoS ONE |
| title | Effect of maternal steroid on developing diaphragm integrity. |
| title_full | Effect of maternal steroid on developing diaphragm integrity. |
| title_fullStr | Effect of maternal steroid on developing diaphragm integrity. |
| title_full_unstemmed | Effect of maternal steroid on developing diaphragm integrity. |
| title_short | Effect of maternal steroid on developing diaphragm integrity. |
| title_sort | effect of maternal steroid on developing diaphragm integrity |
| url | http://europepmc.org/articles/PMC3969349?pdf=render |
| work_keys_str_mv | AT yongsong effectofmaternalsteroidondevelopingdiaphragmintegrity AT deniseldemmer effectofmaternalsteroidondevelopingdiaphragmintegrity AT gavinjpinniger effectofmaternalsteroidondevelopingdiaphragmintegrity AT tinalavin effectofmaternalsteroidondevelopingdiaphragmintegrity AT miavmacmillan effectofmaternalsteroidondevelopingdiaphragmintegrity AT janejpillow effectofmaternalsteroidondevelopingdiaphragmintegrity AT anthonyjbakker effectofmaternalsteroidondevelopingdiaphragmintegrity |