Inheritance of perturbed methylation and metabolism caused by uterine malnutrition via oocytes
Shou-Bin Tang,
Ting-Ting Zhang,
Shen Yin,
Wei Shen,
Shi-Ming Luo,
Yong Zhao,
Cui-Lian Zhang,
Francesca Gioia Klinger,
Qing-Yuan Sun,
Zhao-Jia Ge
Affiliations
Shou-Bin Tang
College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University
Ting-Ting Zhang
College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University
Shen Yin
College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University
Wei Shen
College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University
Shi-Ming Luo
Fertility Preservation Lab and Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital
Yong Zhao
State Key Laboratory of Animal Nutrition, Institute of Animal Sciences, Chinese Academy of Agricultural Sciences
Cui-Lian Zhang
Reproductive Medicine Center, People’s Hospital of Zhengzhou University, Henan Provincial People’s Hospital
Francesca Gioia Klinger
Histology and Embryology, Saint Camillus International University of Health Sciences
Qing-Yuan Sun
Fertility Preservation Lab and Guangdong-Hong Kong Metabolism & Reproduction Joint Laboratory, Reproductive Medicine Center, Guangdong Second Provincial General Hospital
Zhao-Jia Ge
College of Life Sciences, Institute of Reproductive Sciences, Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, Qingdao Agricultural University
Abstract Background Undernourishment in utero has deleterious effects on the metabolism of offspring, but the mechanism of the transgenerational transmission of metabolic disorders is not well known. In the present study, we found that undernourishment in utero resulted in metabolic disorders of female F1 and F2 in mouse model. Results Undernutrition in utero induced metabolic disorders of F1 females, which was transmitted to F2 females. The global methylation in oocytes of F1 exposed to undernutrition in utero was decreased compared with the control. KEGG analysis showed that genes with differential methylation regions (DMRs) in promoters were significantly enriched in metabolic pathways. The altered methylation of some DMRs in F1 oocytes located at the promoters of metabolic-related genes were partially observed in F2 tissues, and the expressions of these genes were also changed. Meanwhile, the abnormal DNA methylation of the validated DMRs in F1 oocytes was also observed in F2 oocytes. Conclusions These results indicate that DNA methylation may mediate the transgenerational inheritance of metabolic disorders induced by undernourishment in utero via female germline.
