Effects of antenatal steroid therapy on neurodevelopment in an IUGR mouse model.
OBJECTIVE
To investigate the neurodevelopmental response in postnatal mice secondary to antenatal steroid treatment in association with maternal protein restriction.


METHODS
C57BL/6N pregnant mice (n = 24; 4 per treatment group) were administered control (C) or protein-restricted (PR) diets and subjected to daily subcutaneous injection stress during late gestation (E10-E17) with either 100 microl/kg of dexamethasone sodium phosphate in normosaline (C-D/S, PR-D/S) or normosaline alone (C-S, PR-S). Non-treatment groups were also included (C, PR). Brain samples of pups were collected on postnatal day 7 and analyzed by immunohistochemistry and qRT-PCR.


RESULTS
Neonatal weights in the treatment groups were smaller than their counterparts in the C group, but there were no significant differences in brain size. Immunohistochemical evaluation of neuroglial cells revealed a pronounced effect of protein restriction on oligodendrocytes and oligodendrocyte precursor cells with distinct fetal responses to stress and dexamethasone. Further evaluation using quantitative RNA analysis showed significant activation of Galr1, Galr2, Igfbp-1, Igfbp-3, Igfbp-6, and Fgf2 by 1- to 2.5-fold in the PR-D/S group and by much higher increments, 1- to 10.5-fold, in the PR-S group.


CONCLUSIONS
This preliminary investigation revealed the possible role of dexamethasone in further increasing vulnerability to cell damage in injury-prone neuroglial cells. The distribution of key glial markers and the overexpression of several neurotrophic factors depicted ongoing cellular adaptation.
Velayo
Clarissa
C
Department of Obstetrics and Gynecology, Tohoku University Graduate School of Medicine, 1-1 Seiryomachi, Aoba-ku, Sendai, Japan. chinkeyvelayo@yahoo.com
Ito
Takuya
T
Chisaka
Hiroshi
H
Yaegashi
Nobuo
N
Okamura
Kunihiro
K
Kimura
Yoshitaka
Y
D000818:Animals; D001253:Astrocytes / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D015415:Biomarkers / Q000378:metabolism; D001921:Brain / Q000187:drug effects / Q000473:pathology; D003907:Dexamethasone / Q000627:therapeutic use*; D018753:Diet, Protein-Restricted; D005260:Female; D005317:Fetal Growth Retardation / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D020567:Fetal Weight / Q000187:drug effects; D007150:Immunohistochemistry; D051379:Mice; D008810:Mice, Inbred C57BL; D009836:Oligodendroglia / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology; D009929:Organ Size / Q000187:drug effects; D011247:Pregnancy; D012333:RNA, Messenger / Q000378:metabolism; D013312:Stress, Physiological
D015415:Biomarkers; D012333:RNA, Messenger; D003907:Dexamethasone