Document Detail


Multigenerational effects of fetal dexamethasone exposure on the hypothalamic-pituitary-adrenal axis of first- and second-generation female offspring.
MedLine Citation:
PMID:  23220271     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
OBJECTIVE: Synthetic glucocorticoid (sGC) administration to women threatening preterm delivery increases neonatal survival. Evidence shows that fetal exposure to glucocorticoid levels higher than appropriate for current maturation programs offspring development. We examined fetal sGC multigenerational effects on F1 and F2 female offspring hypothalamo-pituitary-adrenal axis (HPAA) function.
STUDY DESIGN: At 0.7 gestation, pregnant F0 ewes received 4 dexamethasone injections (2 mg, approximately 60 μg/kg(-1) per day(-1), 12 hours apart) or saline (control). F1 female offspring were bred to produce F2 female offspring. Postpubertal HPAA function was tested in F1 and F2 ewes.
RESULTS: F1 and F2 ewe lambs showed reduced birthweight and morphometrics. Dexamethasone increased baseline but reduced stimulated HPAA activity in F1 and F2 female offspring.
CONCLUSION: This is the first demonstration that sGC doses in the clinical range have multigenerational effects on hypothalamo-pituitary-adrenal activity in a precocial species, indicating the need for the study of long-term effects of fetal sGC exposure.
Authors:
Nathan M Long; Stephen P Ford; Peter W Nathanielsz
Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural     Date:  2012-12-07
Journal Detail:
Title:  American journal of obstetrics and gynecology     Volume:  208     ISSN:  1097-6868     ISO Abbreviation:  Am. J. Obstet. Gynecol.     Publication Date:  2013 Mar 
Date Detail:
Created Date:  2013-02-25     Completed Date:  2013-04-23     Revised Date:  2014-03-07    
Medline Journal Info:
Nlm Unique ID:  0370476     Medline TA:  Am J Obstet Gynecol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  217.e1-8     Citation Subset:  AIM; IM    
Copyright Information:
Copyright © 2013 Mosby, Inc. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Animals
Dexamethasone / pharmacology*
Female
Glucocorticoids / pharmacology*
Hypothalamo-Hypophyseal System / drug effects*,  physiopathology
Hypothalamus / drug effects,  physiopathology
Maternal-Fetal Exchange
Pituitary Gland / drug effects,  physiopathology
Pituitary-Adrenal System / drug effects*,  physiopathology
Pregnancy
Pregnancy, Animal*
Prenatal Exposure Delayed Effects / physiopathology*
Sheep
Grant Support
ID/Acronym/Agency:
HD 21350/HD/NICHD NIH HHS; P01 HD021350/HD/NICHD NIH HHS; P20- RR-16474-04/RR/NCRR NIH HHS
Chemical
Reg. No./Substance:
0/Glucocorticoids; 7S5I7G3JQL/Dexamethasone
Comments/Corrections

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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