Normal epigenetic inheritance in mice conceived by in vitro fertilization and embryo transfer  

作　　者：Lei LI Fang LE Li-ya WANG Xiang-rong XU Hang-ying LOU Ying-ming ZHENG Jiang-zhong SHENG He-feng HUANG Fan JIN 

机构地区：[1]Centre of Reproductive Medicine, Women＇s Hospital, School of Medicine, Zhejiang University, Hangzhou 310006, China [2]Department of Gynecologic Oncology, Henan Cancer Hospital, Zhengzhou 450003, China [3]Department of Cell Biology, School of Medicine, Zhejiang University, Hangzhou 310006, China

出　　处：《Journal of Zhejiang University-Science B(Biomedicine & Biotechnology)》2011年第10期796-804,共9页浙江大学学报（英文版）B辑（生物医学与生物技术）

基　　金：supported by the National Basic Research Program (973) of China (No. 2007CB948104);the National Natural Science Foundation of China (No. 81070532);the Zhejiang Provincial Natural Science Foundation of China (No. Z207021)

摘　　要：An association between assisted reproductive technology （ART） and neurobehavioral imprinting disorders has been reported in many studies, and it seems that ART may interfere with imprint reprogramming. However, it has never been explored whether epigenetic erros or imprinting disease susceptibility induced by ART can be inherited transgenerationally. Hence, the aim of this study was to determine the effect of in vitro fertilization and embryo transfer （IVF-ET） on transgenerational inheritance in am inbred mouse model. Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations. Their behavior, morphology, histology, and DNA methylation status at several important differentially methylated regions （DMRs） were analyzed by Morris water maze, hematoxylin and eosin （H＆E） staining, and bisulfite genomic sequencing. No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF （F1） and female and male line F2 and F3 generations. A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation （0.40±0.118, P=0.086）. Methylation status in H19/Igf2 DMR island 1, Igf2 DMR, KvDMR, and Snrpn DMR displayed normal patterns. Methylation percentage did not differ significantly from that of adults conceived naturally, and the expression of the genes they regulated was not disturbed. Transgenerational integrity, such as behavior, morphology, histology, and DNA methylation status, was maintained in these generations, which indicates that exposure of female germ cells to hormonel stimulation and gamete manipulation might not affect the individuals and their descendents.An association between assisted reproductive technology (ART) and neurobehavioral imprinting disorders has been reported in many studies,and it seems that ART may interfere with imprint reprogramming.However,it has never been explored whether epigenetic errors or imprinting disease susceptibility induced by ART can be inherited transgenerationally.Hence,the aim of this study was to determine the effect of in vitro fertilization and embryo transfer (IVF-ET) on transgenerational inheritance in an inbred mouse model.Mice derived from IVF-ET were outcrossed to wild-type C57BL/6J to obtain their female and male line F2 and F3 generations.Their behavior,morphology,histology,and DNA methylation status at several important differentially methylated regions (DMRs) were analyzed by Morris water maze,hematoxylin and eosin (H&E) staining,and bisulfite genomic sequencing.No significant differences in spatial learning or phenotypic abnormality were found in adults derived from IVF (F1) and female and male line F2 and F3 generations.A borderline trend of hypomethylation was found in H19 DMR CpG island 3 in the female line-derived F3 generation (0.40±0.118,P=0.086).Methylation status in H19/Igf2 DMR island 1,Igf2 DMR,KvDMR,and Snrpn DMR displayed normal patterns.Methylation percentage did not differ significantly from that of adults conceived naturally,and the expression of the genes they regulated was not disturbed.Transgenerational integrity,such as behavior,morphology,histology,and DNA methylation status,was maintained in these generations,which indicates that exposure of female germ cells to hormonal stimulation and gamete manipulation might not affect the individuals and their descendents.

关 键 词：Differentially methylated regions （DMRs）  In vitro fertilization and embryo transfer （IVF-ET）  Centralnervous system （CNS）  Neurobe havioral imprinting disorders  Transgenerational epigenetic inheritance 

分 类 号：R394[医药卫生—医学遗传学]