Paternal transgenerational glucose intolerance with epigenetic alterations in second generation offspring of GDM

• Published in: Asian journal of andrology 2013-07, Vol.15 (4), p.451-452
• Main Authors: Ding, Guo-Lian, Huang, He-Feng
• Format: Article
• Language: English
• Subjects: Animals; Female; Glucose Intolerance; Hyperglycemia - etiology; IGF2; Insulin-Like Growth Factor II - metabolism; Islets of Langerhans - metabolism; Male; Pregnancy; Research Highlight; RNA, Untranslated - metabolism; 后代; 环境异常; 第二代; 胰岛素分泌; 胰岛素抵抗; 葡萄糖; 表观遗传学
• ISSN: 1008-682X; 1745-7262
• DOI: 10.1038/aja.2013.72

Gestational diabetes mellitus （GDM） has been shown to be associated withhigh risk of diabetes in offspring. In addi tion to intergenerational transmission （F1 offspring）, intrauterine hyperglycemia also has effects on the second generation （F2 off spring）. However, the mechanisms involved and the possibilities of transgenerational transmission are still unclear. In a recent study published in Diabetes, we have uti lized GDM mouse model to identify hyper glycemic intrauterine environment causing a high risk of diabetes in offspring by alter ing epigenetic modification. Furthermore, the results indicate that the abnormality of phenotype and imprinted genes expression are more obvious in male offspring than that of female. The changes of epigenetics in sperm may contribute to transgenera tional transmission. A growing body of research suggests that exposure to the abnormal environment in uterus can lead to chronic health problems later in life.1 Intrauterine hyperglycemia is a major characteristic of GDM and has been suggested as an important determinative fac tor for the risk of diabetes in adulthood, it1 addition to the effects of genetic factors.2 The mechanism involved in the association between intrauterine hyperglycemia and a high risk of diabetes in offspring remains unclear.3 In mammals, epigenetic reprogram ming is involved in germ cells and early embryonic development.4＇5 Because erasure and establishment of the genomic imprints for some imprinted genes begin when migra tory primordial germ ceils enter the embry onic genital ridge through gametogenesis, epigenetic abnormalities that occur duringthis phase may be involved in transgenera tional transmission.6 In the study, Ding et al.7 established a GDM mouse model of intrauterine hypergly cemia. The female （9） and male （or） F1 adults of control and GDM mice were intercrossed to obtain F2 offspring of four groups： （i） C0＂ C9; （ii） CCYGDMg; （iii） GDMCrCg; and （iv） GDMcYGDMg. We found that intrau terine hyperglycemia induced impaired glu cose tolerance （IGT） and abnormal insulin levels in F1 offspring, which are partly due to the deficient islet ultrastructure. IGT of male GDM offspring was more obvious than that of female offspring, suggesting that male fetus might be more sensitive to the intrauterine environment than female. Furthermore, the intrauterine hyperglycemia induced transgenerational transmission of glucose intolerance and abnormal insulin levels. In all F2GDM offspring groups, IGT of male