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Changes in 5alpha-pregnane steroids and neurosteroidogenic enzyme expression in fetal sheep with umbilicoplacental embolization.

Abstract：

:Pregnane steroids have sedative and neuroprotective effects on the brain, due to interactions with the steroid-binding site of the GABAA receptor. In the adult brain, synthesis of the pregnane steroids is increased in response to stress. Therefore, we have used umbilicoplacental embolization to mimic chronic placental insufficiency during late gestation in sheep, to investigate the expression of the steroidogenic enzymes p450scc, 5alpha-reductase type I (5alphaRI), 5alpha-reductase type II (5alphaRII), and allopregnanolone (AP) content in the fetal brain. Umbilicoplacental embolization was induced from 114 d gestation (term approximately 147 d) by daily injection of inert microspheres into the umbilical artery and continued for 17-23 d. Fetal arterial oxygen saturation was reduced to approximately 60% of the preembolization value in each fetus, with a significant reduction in blood arterial Po2, pH, and plasma glucose concentrations (p < 0.05) and a significant increase in blood arterial Pco2 and plasma lactate concentrations (p < 0.05). At postmortem at 131-137 d gestation, embolized fetuses were growth-restricted (2.10 +/- 0.14 kg, n = 5) compared with age-matched controls (4.43 +/- 0.56 kg, n = 7, p < 0.05). Umbilicoplacental embolized fetuses showed increased P450scc expression in the primary motor cortex; 5alphaRI expression was not changed in any of the regions examined, whereas 5alphaRII expression was markedly increased in all brain regions. Brain AP content did not significantly change, whereas plasma concentrations were increased. These findings suggest that the increased expression of p450scc and 5alphaRII may be a response that maintains AP concentration in the fetal brain after compromised placental function and/or intrauterine stress.

journal_name

Pediatr Res

journal_title

Pediatric research

authors

Nguyen PN,Billiards SS,Walker DW,Hirst JJ

doi

10.1203/01.PDR.0000088066.47755.36

subject

Has Abstract

pub_date

2003-12-01 00:00:00

pages

840-7

issue

eissn

0031-3998

issn

1530-0447

pii

01.PDR.0000088066.47755.36

journal_volume

pub_type

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Changes in 5alpha-pregnane steroids and neurosteroidogenic enzyme expression in fetal sheep with umbilicoplacental embolization.