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Proceedings Paper

Prevention of congenital defects induced by prenatal alcohol exposure (Conference Presentation)
Author(s): Megan M. Sheehan; Ganga Karunamuni; Cameron J. Pedersen; Shi Gu; Yong Qiu Doughman; Michael W. Jenkins; Michiko Watanabe; Andrew M. Rollins

Paper Abstract

Over 500,000 women per year in the United States drink during pregnancy, and 1 in 5 of this population also binge drink. Up to 40% of live-born children with prenatal alcohol exposure (PAE) present with congenital heart defects (CHDs) including life-threatening outflow and valvuloseptal anomalies. Previously we established a PAE model in the avian embryo and used optical coherence tomography (OCT) imaging to assay looping-stage (early) cardiac function/structure and septation-stage (late) cardiac defects. Early-stage ethanol-exposed embryos had smaller cardiac cushions (valve precursors) and increased retrograde flow, while late-stage embryos presented with gross head/body defects, and exhibited smaller atrio-ventricular (AV) valves, interventricular septae, and aortic vessels. However, supplementation with the methyl donor betaine reduced gross defects, prevented cardiac defects such as ventricular septal defects and abnormal AV valves, and normalized cardiac parameters. Immunofluorescent staining for 5-methylcytosine in transverse embryo sections also revealed that DNA methylation levels were reduced by ethanol but normalized by co-administration of betaine. Furthermore, supplementation with folate, another methyl donor, in the PAE model appeared to normalize retrograde flow levels which are typically elevated by ethanol exposure. Studies are underway to correlate retrograde flow numbers for folate with associated cushion volumes. Finally, preliminary findings have revealed that glutathione, a key endogenous antioxidant which also regulates methyl group donation, is particularly effective in improving alcohol-impacted survival and gross defect rates. Current investigations will determine whether glutathione has any positive effect on PAE-related CHDs. Our studies could have significant implications for public health, especially related to prenatal nutrition recommendations.

Paper Details

Date Published: 19 April 2017
PDF: 1 pages
Proc. SPIE 10043, Diagnosis and Treatment of Diseases in the Breast and Reproductive System, 100430N (19 April 2017);
Show Author Affiliations
Megan M. Sheehan, Case Western Reserve Univ. (United States)
Ganga Karunamuni, Case Western Reserve Univ. (United States)
Cameron J. Pedersen, STERIS Corp. (United States)
Shi Gu, Case Western Reserve Univ. (United States)
Yong Qiu Doughman, Case Western Reserve Univ. (United States)
Michael W. Jenkins, Case Western Reserve Univ. (United States)
Michiko Watanabe, Case Western Reserve Univ. (United States)
Andrew M. Rollins, Case Western Reserve Univ. (United States)


Published in SPIE Proceedings Vol. 10043:
Diagnosis and Treatment of Diseases in the Breast and Reproductive System
Melissa C. Skala; Paul J. Campagnola, Editor(s)

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