Chemoreflex Activity Increases Prostaglandin Endoperoxide Synthase mRNA Expression in the Late-Gestation Fetal Sheep Brain

Wood CE, Rabaglino MB, Richards E, Denslow N, Zarate MA, Chang EI, Keller-Wood M. Transcriptomics of the fetal hypothalamic response to brachiocephalic occlusion and estradiol treatment. Physiol Genomics 46: 523-532, 2014. First published May 13, 2014 doi:10.1152 doi:10. /physiolgenomics.00186.2013 is a wellknown modulator of fetal neuroendocrine activity and has been proposed as a critical endocrine signal readying the fetus for birth and postnatal life. To investigate the modulatory role of E2 on fetal stress responsiveness and the response of the fetal brain to asphyxic stress, we subjected chronically catheterized fetal sheep to a transient (10 min) brachiocephalic artery occlusion (BCO) or sham occlusion. Half of the fetuses received subcutaneous pellets that increased plasma E2 concentrations within the physiological range. Hypothalamic mRNA was analyzed using the Agilent 8x15k ovine array (019921), processed and annotated as previously reported by our laboratory. Analysis of the data by ANOVA revealed that E2 differentially regulated (DR) 561 genes, and BCO DR 894 genes compared with control and E2ϩBCO DR 1,153 genes compared with BCO alone (all P Ͻ 0.05). E2 upregulated epigenetic pathways and downregulated local steroid biosynthesis but did not significantly involve genes known to directly respond to the estrogen receptor. Brachiocephalic occlusion upregulated kinase pathways as well as genes associated with lymphocyte infiltration into the brain and downregulated neuropeptide synthesis. E2 upregulated immune-and apoptosis-related pathways after BCO and reduced kinase and epigenetic pathway responses to the BCO. Responses to BCO are different from responses to hypoxic hypoxia suggesting that mechanisms of responses to these two forms of brain hypoxia are distinct. We conclude that cerebral ischemia caused by BCO might stimulate lymphocyte infiltration into the brain and that this response appears to be modified by estradiol. cortisol; fetal heart; mitochondria; metabolism; late gestation DURING THE TRANSITION FROM intra-to extrauterine life, birth asphyxia is a common cause of cerebral ischemia (29), commonly resulting in the need for resuscitation of the neonate. Disturbances in cerebral blood flow can result from various manipulations in the neonatal intensive care unit, including hypocarbia secondary to mechanical ventilation (18), continuous positive airway pressure (16, 42), and extracorporeal membrane oxygenation (7). Reduction of cerebral blood flow in the neonate compromises oxygen delivery or, if severe, produces ischemia/reperfusion injury (10) and results in morbidity, including intraventricular hemorrhage (6) and long-term cognitive deficit (14).We have investigated the cardiovascular and endocrine responses to cerebral hypoperfusion in late-gestation chronically catheterized fetal sheep (31,38,39), in this animal model of late fetal development. This model allows us to investigate responses to stress in utero and better understand the native homeostatic mechanisms that promote survival af...

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“…spond to our previous report (from these experiments) that BCO increases PTGS2-dependent signaling in the fetal brain (9,40).…”

Section: ϫ16mentioning

confidence: 99%

Transcriptomics of the fetal hypothalamic response to brachiocephalic occlusion and estradiol treatment

Wood

Rabaglino

Richards

et al. 2014

Physiological Genomics

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Estrogen in the Fetus

Wood

2014

Advances in Experimental Medicine and Biology

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Estradiol and other estrogens are important modulators of fetal and maternal physiology in pregnancy. Much is known about the biosynthesis of estrogens in fetus and mother, and much is known about the role that estrogen plays in labor and delivery. However, much less is known about the regulation of estrogen biosynthesis throughout the latter half of gestation, and the role that estrogen plays in homeostatic and neuroendocrine control in the fetus. This review focuses on the biosynthesis and actions of estrogen in the fetal circulation, the role that it plays in the development of the fetus in the latter half of gestation, and the role that is played by the estrogen milieu in the control of the timing of birth. Estrogen circulates in fetal blood in both unconjugated and conjugated molecular forms, with the conjugated steroids far more abundant than the unconjugated steroids. This review therefore also addresses the biological significance of the variety of molecular forms of estrogen circulating in fetal and maternal blood.

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Chemoreflex Activity Increases Prostaglandin Endoperoxide Synthase mRNA Expression in the Late-Gestation Fetal Sheep Brain

Cited by 2 publications

References 47 publications

Transcriptomics of the fetal hypothalamic response to brachiocephalic occlusion and estradiol treatment

Transcriptomics of the fetal hypothalamic response to brachiocephalic occlusion and estradiol treatment

Estrogen in the Fetus

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