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Hyperglycemia alters retinoic acid catabolism in embryos exposed to a maternal diabetic milieu

Pregestational diabetes is highly associated with increased risk of birth defects. We previously reported that the expression of Cyp26a1, the major catabolizing enzyme for controlling retinoic acid (RA) homeostasis, is significantly down-regulated in embryos of diabetic mice, thereby increasing the...

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Autores principales: Lee, Leo Man Yuen, Leung, Yun-chung, Shum, Alisa Sau Wun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Public Library of Science 2023
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449132/
https://www.ncbi.nlm.nih.gov/pubmed/37616226
http://dx.doi.org/10.1371/journal.pone.0287253
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author Lee, Leo Man Yuen
Leung, Yun-chung
Shum, Alisa Sau Wun
author_facet Lee, Leo Man Yuen
Leung, Yun-chung
Shum, Alisa Sau Wun
author_sort Lee, Leo Man Yuen
collection PubMed
description Pregestational diabetes is highly associated with increased risk of birth defects. We previously reported that the expression of Cyp26a1, the major catabolizing enzyme for controlling retinoic acid (RA) homeostasis, is significantly down-regulated in embryos of diabetic mice, thereby increasing the embryo’s susceptibility to malformations caused by RA dysregulation. However, the underlying mechanism for the down-regulation of Cyp26a1 remains unclear. This study aimed to investigate whether elevated maternal blood glucose in the diabetic milieu is a critical factor for the altered Cyp26a1 expression. Streptozotozin-induced diabetic pregnant mice were treated with phlorizin (PHZ) to reduce blood glucose concentrations via induction of renal glucosuria. Embryonic Cyp26a1 expression level, RA catabolic activity and susceptibility to various RA-induced abnormalities were examined. To test the dose-dependent effect of glucose on Cyp26a1 level, early head-fold stage rat embryos of normal pregnancy were cultured in vitro with varying concentrations of D-glucose, followed by quantification of Cyp26a1 transcripts. We found that Cyp26a1 expression, which was down-regulated in diabetic pregnancy, could be normalized under reduced maternal blood glucose level, concomitant with an increase in RA catabolic activity in embryonic tissues. Such normalization could successfully reduce the susceptibility to different RA-induced malformations including caudal regression, cleft palate and renal malformations. The expression level of Cyp26a1 in the embryo was inversely correlated with D-glucose concentrations. Diabetic patients suffer from retinopathy, dermopathy, male infertility and increased cancer risk. Coincidentally, RA dysregulation is also associated with these health problems. Our results provided evidence that elevated glucose can down-regulate Cyp26a1 expression level and disturb RA homeostasis, shedding light on the possibility of affecting the health of diabetic patients via a similar mechanism.
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spelling pubmed-104491322023-08-25 Hyperglycemia alters retinoic acid catabolism in embryos exposed to a maternal diabetic milieu Lee, Leo Man Yuen Leung, Yun-chung Shum, Alisa Sau Wun PLoS One Research Article Pregestational diabetes is highly associated with increased risk of birth defects. We previously reported that the expression of Cyp26a1, the major catabolizing enzyme for controlling retinoic acid (RA) homeostasis, is significantly down-regulated in embryos of diabetic mice, thereby increasing the embryo’s susceptibility to malformations caused by RA dysregulation. However, the underlying mechanism for the down-regulation of Cyp26a1 remains unclear. This study aimed to investigate whether elevated maternal blood glucose in the diabetic milieu is a critical factor for the altered Cyp26a1 expression. Streptozotozin-induced diabetic pregnant mice were treated with phlorizin (PHZ) to reduce blood glucose concentrations via induction of renal glucosuria. Embryonic Cyp26a1 expression level, RA catabolic activity and susceptibility to various RA-induced abnormalities were examined. To test the dose-dependent effect of glucose on Cyp26a1 level, early head-fold stage rat embryos of normal pregnancy were cultured in vitro with varying concentrations of D-glucose, followed by quantification of Cyp26a1 transcripts. We found that Cyp26a1 expression, which was down-regulated in diabetic pregnancy, could be normalized under reduced maternal blood glucose level, concomitant with an increase in RA catabolic activity in embryonic tissues. Such normalization could successfully reduce the susceptibility to different RA-induced malformations including caudal regression, cleft palate and renal malformations. The expression level of Cyp26a1 in the embryo was inversely correlated with D-glucose concentrations. Diabetic patients suffer from retinopathy, dermopathy, male infertility and increased cancer risk. Coincidentally, RA dysregulation is also associated with these health problems. Our results provided evidence that elevated glucose can down-regulate Cyp26a1 expression level and disturb RA homeostasis, shedding light on the possibility of affecting the health of diabetic patients via a similar mechanism. Public Library of Science 2023-08-24 /pmc/articles/PMC10449132/ /pubmed/37616226 http://dx.doi.org/10.1371/journal.pone.0287253 Text en © 2023 Lee et al https://creativecommons.org/licenses/by/4.0/This is an open access article distributed under the terms of the Creative Commons Attribution License (https://creativecommons.org/licenses/by/4.0/) , which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
spellingShingle Research Article
Lee, Leo Man Yuen
Leung, Yun-chung
Shum, Alisa Sau Wun
Hyperglycemia alters retinoic acid catabolism in embryos exposed to a maternal diabetic milieu
title Hyperglycemia alters retinoic acid catabolism in embryos exposed to a maternal diabetic milieu
title_full Hyperglycemia alters retinoic acid catabolism in embryos exposed to a maternal diabetic milieu
title_fullStr Hyperglycemia alters retinoic acid catabolism in embryos exposed to a maternal diabetic milieu
title_full_unstemmed Hyperglycemia alters retinoic acid catabolism in embryos exposed to a maternal diabetic milieu
title_short Hyperglycemia alters retinoic acid catabolism in embryos exposed to a maternal diabetic milieu
title_sort hyperglycemia alters retinoic acid catabolism in embryos exposed to a maternal diabetic milieu
topic Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10449132/
https://www.ncbi.nlm.nih.gov/pubmed/37616226
http://dx.doi.org/10.1371/journal.pone.0287253
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