Intrauterine hyperglycemia impairs memory across two generations

Studies on humans and animals suggest associations between gestational diabetes mellitus (GDM) with increased susceptibility to develop neurological disorders in offspring. However, the molecular mechanisms underpinning the intergenerational effects remain unclear. Using a mouse model of diabetes du...

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Autores principales: Zou, Kexin, Ren, Jun, Luo, Sisi, Zhang, Junyu, Zhou, Chengliang, Tan, Chengxi, Lv, Pingping, Sun, Xiao, Sheng, Jianzhong, Liu, Xinmei, Huang, Hefeng, Ding, Guolian
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2021
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Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379206/
https://www.ncbi.nlm.nih.gov/pubmed/34417446
http://dx.doi.org/10.1038/s41398-021-01565-7
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author Zou, Kexin
Ren, Jun
Luo, Sisi
Zhang, Junyu
Zhou, Chengliang
Tan, Chengxi
Lv, Pingping
Sun, Xiao
Sheng, Jianzhong
Liu, Xinmei
Huang, Hefeng
Ding, Guolian
author_facet Zou, Kexin
Ren, Jun
Luo, Sisi
Zhang, Junyu
Zhou, Chengliang
Tan, Chengxi
Lv, Pingping
Sun, Xiao
Sheng, Jianzhong
Liu, Xinmei
Huang, Hefeng
Ding, Guolian
author_sort Zou, Kexin
collection PubMed
description Studies on humans and animals suggest associations between gestational diabetes mellitus (GDM) with increased susceptibility to develop neurological disorders in offspring. However, the molecular mechanisms underpinning the intergenerational effects remain unclear. Using a mouse model of diabetes during pregnancy, we found that intrauterine hyperglycemia exposure resulted in memory impairment in both the first filial (F1) males and the second filial (F2) males from the F1 male offspring. Transcriptome profiling of F1 and F2 hippocampi revealed that differentially expressed genes (DEGs) were enriched in neurodevelopment and synaptic plasticity. The reduced representation bisulfite sequencing (RRBS) of sperm in F1 adult males showed that the intrauterine hyperglycemia exposure caused altered methylated modification of F1 sperm, which is a potential epigenetic mechanism for the intergenerational neurocognitive effects of GDM.
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spelling pubmed-83792062021-09-08 Intrauterine hyperglycemia impairs memory across two generations Zou, Kexin Ren, Jun Luo, Sisi Zhang, Junyu Zhou, Chengliang Tan, Chengxi Lv, Pingping Sun, Xiao Sheng, Jianzhong Liu, Xinmei Huang, Hefeng Ding, Guolian Transl Psychiatry Article Studies on humans and animals suggest associations between gestational diabetes mellitus (GDM) with increased susceptibility to develop neurological disorders in offspring. However, the molecular mechanisms underpinning the intergenerational effects remain unclear. Using a mouse model of diabetes during pregnancy, we found that intrauterine hyperglycemia exposure resulted in memory impairment in both the first filial (F1) males and the second filial (F2) males from the F1 male offspring. Transcriptome profiling of F1 and F2 hippocampi revealed that differentially expressed genes (DEGs) were enriched in neurodevelopment and synaptic plasticity. The reduced representation bisulfite sequencing (RRBS) of sperm in F1 adult males showed that the intrauterine hyperglycemia exposure caused altered methylated modification of F1 sperm, which is a potential epigenetic mechanism for the intergenerational neurocognitive effects of GDM. Nature Publishing Group UK 2021-08-20 /pmc/articles/PMC8379206/ /pubmed/34417446 http://dx.doi.org/10.1038/s41398-021-01565-7 Text en © The Author(s) 2021 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons license, and indicate if changes were made. The images or other third party material in this article are included in the article’s Creative Commons license, unless indicated otherwise in a credit line to the material. If material is not included in the article’s Creative Commons license and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this license, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Zou, Kexin
Ren, Jun
Luo, Sisi
Zhang, Junyu
Zhou, Chengliang
Tan, Chengxi
Lv, Pingping
Sun, Xiao
Sheng, Jianzhong
Liu, Xinmei
Huang, Hefeng
Ding, Guolian
Intrauterine hyperglycemia impairs memory across two generations
title Intrauterine hyperglycemia impairs memory across two generations
title_full Intrauterine hyperglycemia impairs memory across two generations
title_fullStr Intrauterine hyperglycemia impairs memory across two generations
title_full_unstemmed Intrauterine hyperglycemia impairs memory across two generations
title_short Intrauterine hyperglycemia impairs memory across two generations
title_sort intrauterine hyperglycemia impairs memory across two generations
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8379206/
https://www.ncbi.nlm.nih.gov/pubmed/34417446
http://dx.doi.org/10.1038/s41398-021-01565-7
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