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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2014

Open Access 01-12-2014 | Research

Maternal obesity and diabetes may cause DNA methylation alteration in the spermatozoa of offspring in mice

Authors: Zhao-Jia Ge, Qiu-Xia Liang, Yi Hou, Zhi-Ming Han, Heide Schatten, Qing-Yuan Sun, Cui-Lian Zhang

Published in: Reproductive Biology and Endocrinology | Issue 1/2014

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Abstract

Background

The adverse effects on offspring of diabetic and/or obese mothers can be passed to the next generation. However, the mechanisms behind this are still unclear. Epigenetics may play a key role during this process.

Methods

To confirm the hypothesis, we investigated the DNA methylation of several imprinted genes in spermatozoa of offspring from diabetic and/or obese mothers utilizing streptozotocin (STZ)- and high-fat-diet (HFD)-induced mouse models.

Results

We found that the DNA methylation of Peg3 was significantly increased in spermatozoa of offspring of obese mothers compared to that in spermatozoa of offspring of normal mothers. The DNA methylation of H19 was significantly higher in spermatozoa of offspring of diabetic mothers than that in spermatozoa of offspring of non-diabetic mothers.

Conclusions

These results indicate that pre-gestational diabetes and/or obesity can alter DNA methylation in offspring spermatozoa.
Appendix
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Literature
1.
Cox NJ: Maternal component in NIDDM transmission. How large an effect?. Diabetes. 1994, 43: 166-168. 10.2337/diab.43.1.166.CrossRefPubMed
2.
Evers IM, de Valk HW, Visser GH: Risk of complications of pregnancy in women with type 1 diabetes: nationwide prospective study in the Netherlands. BMJ. 2004, 328: 915-10.1136/bmj.38043.583160.EE.PubMedCentralCrossRefPubMed
3.
4.
Moley KH, Chi MM, Manchester JK, McDougal DB, Lowry OH: Alterations of intraembryonic metabolites in preimplantation mouse embryos exposed to elevated concentrations of glucose: a metabolic explanation for the developmental retardation seen in preimplantation embryos from diabetic animals. Biol Reprod. 1996, 54: 1209-1216. 10.1095/biolreprod54.6.1209.CrossRefPubMed
5.
Sadler TW, Hunter ES, Balkan W, Horton WE: Effects of maternal diabetes on embryogenesis. Am J Perinatol. 1988, 5: 319-326. 10.1055/s-2007-999717.CrossRefPubMed
6.
Yessoufou A, Moutairou K: Maternal diabetes in pregnancy: early and long-term outcomes on the offspring and the concept of “metabolic memory”. Exp Diabetes Res. 2011, 2011: 218598-PubMedCentralCrossRefPubMed
7.
Aerts L, Holemans K, Van Assche FA: Maternal diabetes during pregnancy: consequences for the offspring. Diabetes Metab Rev. 1990, 6: 147-167. 10.1002/dmr.5610060303.CrossRefPubMed
8.
Dorner G, Plagemann A: Perinatal hyperinsulinism as possible predisposing factor for diabetes mellitus, obesity and enhanced cardiovascular risk in later life. Horm Metab Res. 1994, 26: 213-221. 10.1055/s-2007-1001668.CrossRefPubMed
9.
Howie GJ, Sloboda DM, Kamal T, Vickers MH: Maternal nutritional history predicts obesity in adult offspring independent of postnatal diet. J Physiol. 2009, 587: 905-915. 10.1113/jphysiol.2008.163477.PubMedCentralCrossRefPubMed
10.
Whitaker RC: Predicting preschooler obesity at birth: the role of maternal obesity in early pregnancy. Pediatrics. 2004, 114: e29-36. 10.1542/peds.114.1.e29.CrossRefPubMed
11.
Lawlor DA, Lichtenstein P, Fraser A, Langstrom N: Does maternal weight gain in pregnancy have long-term effects on offspring adiposity? A sibling study in a prospective cohort of 146,894 men from 136,050 families. Am J Clin Nutr. 2011, 94: 142-148. 10.3945/ajcn.110.009324.PubMedCentralCrossRefPubMed
12.
Shankar K, Harrell A, Liu X, Gilchrist JM, Ronis MJ, Badger TM: Maternal obesity at conception programs obesity in the offspring. Am J Physiol Regul Integr Comp Physiol. 2008, 294: R528-538.CrossRefPubMed
13.
Bayol SA, Farrington SJ, Stickland NC: A maternal ‘junk food’ diet in pregnancy and lactation promotes an exacerbated taste for ‘junk food’ and a greater propensity for obesity in rat offspring. Br J Nutr. 2007, 98: 843-851.CrossRefPubMed
14.
Pentinat T, Ramon-Krauel M, Cebria J, Diaz R, Jimenez-Chillaron JC: Transgenerational inheritance of glucose intolerance in a mouse model of neonatal overnutrition. Endocrinology. 2010, 151: 5617-5623. 10.1210/en.2010-0684.CrossRefPubMed
15.
Dabelea D, Hanson RL, Lindsay RS, Pettitt DJ, Imperatore G, Gabir MM, Roumain J, Bennett PH, Knowler WC: Intrauterine exposure to diabetes conveys risks for type 2 diabetes and obesity: a study of discordant sibships. Diabetes. 2000, 49: 2208-2211. 10.2337/diabetes.49.12.2208.CrossRefPubMed
16.
Dunn GA, Bale TL: Maternal high-fat diet promotes body length increases and insulin insensitivity in second-generation mice. Endocrinology. 2009, 150: 4999-5009. 10.1210/en.2009-0500.PubMedCentralCrossRefPubMed
17.
Dunn GA, Bale TL: Maternal high-fat diet effects on third-generation female body size via the paternal lineage. Endocrinology. 2011, 152: 2228-2236. 10.1210/en.2010-1461.PubMedCentralCrossRefPubMed
18.
Ge ZJ, Liang XW, Guo L, Liang QX, Luo SM, Wang YP, Wei YC, Han ZM, Schatten H, Sun QY: Maternal diabetes causes alterations of DNA methylation statuses of some imprinted genes in murine oocytes. Biol Reprod. 2013, 88: 117-10.1095/biolreprod.112.105981.CrossRefPubMed
19.
Ge ZJ, Luo SM, Lin F, Liang QX, Huang L, Wei YC, Hou Y, Han ZM, Schatten H, Sun QY: DNA methylation in oocytes and liver of female mice and their offspring: effects of high-fat-diet-induced obesity. Environ Health Perspect. 2014, 122: 159-164.PubMedCentralPubMed
20.
Wei Y, Yang CR, Wei YP, Zhao ZA, Hou Y, Schatten H, Sun QY: Paternally induced transgenerational inheritance of susceptibility to diabetes in mammals. Proc Natl Acad Sci U S A. 2014, 111: 1873-1878. 10.1073/pnas.1321195111.PubMedCentralCrossRefPubMed
21.
Stouder C, Deutsch S, Paoloni-Giacobino A: Superovulation in mice alters the methylation pattern of imprinted genes in the sperm of the offspring. Reprod Toxicol. 2009, 28: 536-541. 10.1016/j.reprotox.2009.06.009.CrossRefPubMed
22.
Li E, Beard C, Jaenisch R: Role for DNA methylation in genomic imprinting. Nature. 1993, 366: 362-365. 10.1038/366362a0.CrossRefPubMed
23.
Kaneda M, Okano M, Hata K, Sado T, Tsujimoto N, Li E, Sasaki H: Essential role for de novo DNA methyltransferase Dnmt3a in paternal and maternal imprinting. Nature. 2004, 429: 900-903. 10.1038/nature02633.CrossRefPubMed
24.
Kohler C, Weinhofer-Molisch I: Mechanisms and evolution of genomic imprinting in plants. Heredity (Edinb). 2010, 105: 57-63. 10.1038/hdy.2009.176.CrossRef
25.
Wutz A, Smrzka OW, Schweifer N, Schellander K, Wagner EF, Barlow DP: Imprinted expression of the Igf2r gene depends on an intronic CpG island. Nature. 1997, 389: 745-749. 10.1038/39631.CrossRefPubMed
26.
Thorvaldsen JL, Duran KL, Bartolomei MS: Deletion of the H19 differentially methylated domain results in loss of imprinted expression of H19 and Igf2. Genes Dev. 1998, 12: 3693-3702. 10.1101/gad.12.23.3693.PubMedCentralCrossRefPubMed
27.
Fitzpatrick GV, Soloway PD, Higgins MJ: Regional loss of imprinting and growth deficiency in mice with a targeted deletion of KvDMR1. Nat Genet. 2002, 32: 426-431. 10.1038/ng988.CrossRefPubMed
28.
Lee J, Inoue K, Ono R, Ogonuki N, Kohda T, Kaneko-Ishino T, Ogura A, Ishino F: Erasing genomic imprinting memory in mouse clone embryos produced from day 11.5 primordial germ cells. Dev. 2002, 129: 1807-1817.CrossRef
29.
Hajkova P, Erhardt S, Lane N, Haaf T, El-Maarri O, Reik W, Walter J, Surani MA: Epigenetic reprogramming in mouse primordial germ cells. Mech Dev. 2002, 117: 15-23. 10.1016/S0925-4773(02)00181-8.CrossRefPubMed
30.
Li JY, Lees-Murdock DJ, Xu GL, Walsh CP: Timing of establishment of paternal methylation imprints in the mouse. Genomics. 2004, 84: 952-960. 10.1016/j.ygeno.2004.08.012.CrossRefPubMed
31.
Lucifero D, Mertineit C, Clarke HJ, Bestor TH, Trasler JM: Methylation dynamics of imprinted genes in mouse germ cells. Genomics. 2002, 79: 530-538. 10.1006/geno.2002.6732.CrossRefPubMed
32.
Lucifero D, Mann MR, Bartolomei MS, Trasler JM: Gene-specific timing and epigenetic memory in oocyte imprinting. Hum Mol Genet. 2004, 13: 839-849. 10.1093/hmg/ddh104.CrossRefPubMed
33.
Hiura H, Obata Y, Komiyama J, Shirai M, Kono T: Oocyte growth-dependent progression of maternal imprinting in mice. Genes Cells. 2006, 11: 353-361. 10.1111/j.1365-2443.2006.00943.x.CrossRefPubMed
34.
Davis TL, Trasler JM, Moss SB, Yang GJ, Bartolomei MS: Acquisition of the H19 methylation imprint occurs differentially on the parental alleles during spermatogenesis. Genomics. 1999, 58: 18-28. 10.1006/geno.1999.5813.CrossRefPubMed
35.
Ueda T, Abe K, Miura A, Yuzuriha M, Zubair M, Noguchi M, Niwa K, Kawase Y, Kono T, Matsuda Y, Fujimoto H, Shibata H, Hayashizaki Y, Sasaki H: The paternal methylation imprint of the mouse H19 locus is acquired in the gonocyte stage during foetal testis development. Genes Cells. 2000, 5: 649-659. 10.1046/j.1365-2443.2000.00351.x.CrossRefPubMed
36.
Kato Y, Kaneda M, Hata K, Kumaki K, Hisano M, Kohara Y, Okano M, Li E, Nozaki M, Sasaki H: Role of the Dnmt3 family in de novo methylation of imprinted and repetitive sequences during male germ cell development in the mouse. Hum Mol Genet. 2007, 16: 2272-2280. 10.1093/hmg/ddm179.CrossRefPubMed
37.
Lehavi O, Aizenstein O, Evans MI, Yaron Y: 2nd-trimester maternal serum human chorionic gonadotropin and alpha-fetoprotein levels in male and female fetuses with Down syndrome. Fetal Diagn Ther. 2005, 20: 235-238. 10.1159/000083911.CrossRefPubMed
38.
Steier JA, Bergsjo PB, Thorsen T, Myking OL: Human chorionic gonadotropin in maternal serum in relation to fetal gender and utero-placental blood flow. Acta Obstet Gynecol Scand. 2004, 83: 170-174. 10.1080/j.0001-6349.2004.00407.x.CrossRefPubMed
39.
Gallou-Kabani C, Gabory A, Tost J, Karimi M, Mayeur S, Lesage J, Boudadi E, Gross MS, Taurelle J, Vige A, Breton C, Reusens B, Remacle C, Vieau D, Ekström TJ, Jais JP, Junien C: Sex- and diet-specific changes of imprinted gene expression and DNA methylation in mouse placenta under a high-fat diet. PLoS One. 2010, 5: e14398-10.1371/journal.pone.0014398.PubMedCentralCrossRefPubMed
40.
Mao J, Zhang X, Sieli PT, Falduto MT, Torres KE, Rosenfeld CS: Contrasting effects of different maternal diets on sexually dimorphic gene expression in the murine placenta. Proc Natl Acad Sci U S A. 2010, 107: 5557-5562. 10.1073/pnas.1000440107.PubMedCentralCrossRefPubMed
41.
McPherson FJ, Chenoweth PJ: Mammalian sexual dimorphism. Anim Reprod Sci. 2012, 131: 109-122. 10.1016/j.anireprosci.2012.02.007.CrossRefPubMed
42.
Amorim EMP, Damasceno DC, Perobelli JE, Spadotto R, Fernandez CDB, Volpato GT, Kempinas WDG: Short- and long-term reproductive effects of prenatal and lactational growth restriction caused by maternal diabetes in male rats. Reprod Biol Endocrinol. 2011, 9: 154-10.1186/1477-7827-9-154.PubMedCentralCrossRefPubMed
43.
Jelodar G, Khaksar Z, Pourahmadi M: Endocrine profile and testicular histomorphometry in adult rat offspring of diabetic mothers. J Physiol Sci. 2009, 59: 377-382. 10.1007/s12576-009-0045-7.CrossRefPubMed
44.
Ding GL, Wang FF, Shu J, Tian S, Jiang Y, Zhang D, Wang N, Luo Q, Zhang Y, Jin F, Leung PC, Sheng JZ, Huang HF: Transgenerational glucose intolerance with Igf2/H19 epigenetic alterations in mouse islet induced by intrauterine hyperglycemia. Diabetes. 2012, 61: 1133-1142. 10.2337/db11-1314.PubMedCentralCrossRefPubMed
Metadata
Title
Maternal obesity and diabetes may cause DNA methylation alteration in the spermatozoa of offspring in mice
Authors
Zhao-Jia Ge
Qiu-Xia Liang
Yi Hou
Zhi-Ming Han
Heide Schatten
Qing-Yuan Sun
Cui-Lian Zhang
Publication date
01-12-2014
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2014
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/1477-7827-12-29

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