Intrauterine hyperglycemia impairs memory across two generations

Kexin Zou; Jun Ren; Sisi Luo; Junyu Zhang; Chengliang Zhou; Chengxi Tan; Pingping Lv; Xiao Sun; Jianzhong Sheng; Xinmei Liu; Hefeng Huang; Guolian Ding

doi:10.1038/s41398-021-01565-7

Intrauterine hyperglycemia impairs memory across two generations

Transl Psychiatry. 2021 Aug 20;11(1):434. doi: 10.1038/s41398-021-01565-7.

Authors

Kexin Zou^#^{1

2

3}, Jun Ren^#⁴, Sisi Luo^{1

2

3}, Junyu Zhang^{1

2

3}, Chengliang Zhou^{1

2

3}, Chengxi Tan¹, Pingping Lv⁴, Xiao Sun^{1

2

3}, Jianzhong Sheng⁴, Xinmei Liu^{2

3

5}, Hefeng Huang^{6

7

8

9}, Guolian Ding^{10

11

12}

Affiliations

¹ The International Peace Maternity and Child Health Hospital, School of Medicine, Shanghai Jiao Tong University, Shanghai, China.
² Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China.
³ Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China.
⁴ Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China.
⁵ Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China.
⁶ Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China. huanghefg@hotmail.com.
⁷ Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China. huanghefg@hotmail.com.
⁸ Key Laboratory of Reproductive Genetics (Ministry of Education), Department of Reproductive Endocrinology, Women's Hospital, Zhejiang University School of Medicine, Hangzhou, China. huanghefg@hotmail.com.
⁹ Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China. huanghefg@hotmail.com.
¹⁰ Shanghai Key Laboratory of Embryo Original Diseases, Shanghai, China. dingguolian@hotmail.com.
¹¹ Research Units of Embryo Original Diseases, Chinese Academy of Medical Sciences, Shanghai, China. dingguolian@hotmail.com.
¹² Obstetrics and Gynecology Hospital, Institute of Reproduction and Development, Fudan University, Shanghai, China. dingguolian@hotmail.com.

^# Contributed equally.

Abstract

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.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Diabetes, Gestational* / genetics
Epigenesis, Genetic
Female
Hyperglycemia* / complications
Hyperglycemia* / genetics
Male
Pregnancy
Prenatal Exposure Delayed Effects* / genetics