Calcium-Deficient Diets in Pregnancy and Nursing: Epigenetic Change in Three Generations of Offspring

  • Junji TakayaEmail author
Reference work entry


Prenatal malnutrition can affect the phenotype of offspring by changing epigenetic regulation. Calcium (Ca) plays an important role in the pathogenesis of insulin resistance syndrome. We previously reported that feeding a Ca-restricted diet to pregnant rats results in hypomethylation and decreased expression from the 11β-hydroxysteroid dehydrogenase-1 promoter in the liver of offspring at day 21. These findings show that a maternal Ca deficiency during pregnancy can affect the regulation of non-imprinted genes by altering the epigenetic regulation of gene expression, thereby inducing different metabolic phenotypes. The epigenome is an important target of environmental modification. In addition, we determined the effects of a Ca deficiency during pregnancy and/or lactation on insulin resistance and secretion in at least three generations. Female Wistar rats consumed either a Ca-deficient or control diet ad libitum from three weeks preconception to 21 days postparturition and were mated with control males. Randomly selected first (F1)- and second-generation (F2) females were mated with males of each generation on postnatal day 70. F1 and F2 dams were fed with a control diet ad libitum during pregnancy and lactation. On 180 days, homeostasis model assessment of beta cell function (HOMA-β%) gradually decreased in F1 through F3 and that in F2 and F3 males and females was significantly lower than control. These findings indicated that maternal Ca restriction during pregnancy and/or lactation influences insulin secretion in three generations of offspring.


Calcium Glucocorticoid receptor HOMA-IR HOMA-β% Insulin resistance Metabolic syndrome Pregnancy Pyrosequencing Rat 11β-Hydroxysteroid dehydrogenase-1 

List of Abbreviations




First generation


Second generation


Third generation


Glucocorticoid receptor


Homeostasis model assessment of insulin resistance


Homeostasis model assessment of beta cell function


11β-hydroxysteroid dehydrogenase-1


11β-hydroxysteroid dehydrogenase-2


11β-hydroxysteroid dehydrogenase-1 gene


11β-hydroxysteroid dehydrogenase-2 gene


glucocorticoid receptor gene


phosphoenolpyruvate carboxykinase


phosphoenolpyruvate carboxykinase gene


peroxisome proliferator-activated receptor α


rat peroxisome proliferator-activated receptor α gene


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Copyright information

© Springer Nature Switzerland AG 2019

Authors and Affiliations

  1. 1.Department of PediatricsKawachi General HospitalHigashi-OsakaJapan
  2. 2.Department of PediatricsKansai Medical UniversityMoriguchiJapan

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