The DNA methylation profile of oocytes in mice with hyperinsulinaemia and hyperandrogenism as detected by single-cell level whole genome bisulphite sequencing (SC-WGBS) technology
Qian-Nan Li A B , Lei Guo C , Yi Hou B , Xiang-Hong Ou C , Zhonghua Liu A and Qing-Yuan Sun A B D EA College of Life Science, Northeast Agricultural University, #600 Changjiang Road, Harbin 150030, China.
B State Key Laboratory of Stem Cell and Reproductive Biology, Institute of Zoology, Chinese Academy of Sciences, #1 Beichen West Road, Beijing 100101, China.
C Fertility Preservation Lab, Reproductive Medicine Centre, Guangdong Second Provincial General Hospital, The Second Peoples’ Hospital of Guangdong Province, #466 Xingang Road, Guangzhou 510317, China.
D Qingdao Agricultural University, #700 Changcheng Road, Qingdao 266109, China.
E Corresponding author. Email: sunqy@ioz.ac.cn
Reproduction, Fertility and Development 30(12) 1713-1719 https://doi.org/10.1071/RD18002
Submitted: 2 January 2018 Accepted: 16 May 2018 Published: 22 June 2018
Abstract
Polycystic ovary syndrome (PCOS), a familial aggregation disease that causes anovulation in women, has well-recognised characteristics, two of which are hyperinsulinaemia and hyperandrogenaemia. To determine whether the DNA methylation status is altered in oocytes by high insulin and androgen levels, we generated a mouse model with hyperinsulinaemia and hyperandrogenaemia by injection of insulin and human chorionic gonadotrophin and investigated DNA methylation changes through single-cell level whole genome bisulphite sequencing. Our results showed that hyperinsulinaemia and hyperandrogenaemia had no significant effects on the global DNA methylation profile and different functional regions of genes, but did alter methylation status of some genes, which were significantly enriched in 17 gene ontology (GO) terms (P < 0.05) by GO analysis. Among differently methylated genes, some were related to the occurrence of PCOS. Based on our results, we suggest that hyperinsulinaemia and hyperandrogenaemia may cause changes in some DNA methylation loci in oocytes.
Additional keywords: assisted reproduction, fertility, hyperandrogenaemia, insulin, mouse model, PCOS.
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