Progressive, Transgenerational Changes in Offspring Phenotype and Epigenotype following Nutritional Transition

Abstract

Induction of altered phenotypes during development in response to environmental input involves epigenetic changes. Phenotypic traits can be passed between generations by a variety of mechanisms, including direct transmission of epigenetic states or by induction of epigenetic marks de novo in each generation. To distinguish between these possibilities we measured epigenetic marks over four generations in rats exposed to a sustained environmental challenge. Dietary energy was increased by 25% at conception in F0 female rats and maintained at this level to generation F3. F0 dams showed higher pregnancy weight gain, but lower weight gain and food intake during lactation than F1 and F2 dams. On gestational day 8, fasting plasma glucose concentration was higher and β-hydroxybutyrate lower in F0 and F1 dams than F2 dams. This was accompanied by decreased phosphoenolpyruvate carboxykinase (PEPCK) and increased PPARα and carnitine palmitoyl transferase-1 mRNA expression. PEPCK mRNA expression was inversely related to the methylation of specific CpG dinucleotides in its promoter. DNA methyltransferase (Dnmt) 3a2, but not Dnmt1 or Dnmt3b, expression increased and methylation of its promoter decreased from F1 to F3 generations. These data suggest that the regulation of energy metabolism during pregnancy and lactation within a generation is influenced by the maternal phenotype in the preceding generation and the environment during the current pregnancy. The transgenerational effects on phenotype were associated with altered DNA methylation of specific genes in a manner consistent with induction de novo of epigenetic marks in each generation.

Smoking induces differential miRNA expression in human spermatozoa: A potential transgenerational epigenetic concern?

“…Four of these miRNAs (hsa-miR-146b-5p, hsamiR-509-5p, hsa-miR-519d and hsa-miR-652) have already been shown to be altered in the testes, seminal plasma and/or semen environmental toxins and factors) can induce harmful phenotypes in the descendants of exposed individuals. [6][7][8][9][10][11][12][13][14] Although the mechanisms underlying transmission of environmentallyinduced phenotypes through generations are not well understood, epigenetic changes within the germ line appear to play a central role. The association of DNA methylation with environmental exposures and heritable phenotypes has been widely established.…”

“…6,7 Such multigenerational toxicity has been observed following exposure to other environmental chemicals and environmental factors such as nutrition and stress. [8][9][10][11][12][13][14] Epidemiological studies suggest that this phenomenon may also occur in human populations. [15][16][17][18][19] recent work has suggested that environmental chemicals, including those contained in cigarette smoke, can have adverse effects on the exposed individuals as well as their future progeny.…”

Indeks Massa Tubuh Awal Kehamilan Ibu sebagai Indikator yang Paling Berperan terhadap Kenaikan Berat Badan Ibu Selama Hamil

“…17,18 Data memperlihatkan bahwa regulasi metabolism energi selama kehamilan pada satu generasi dipengaruhi oleh fenotipe maternal generasi sebelumnya dan lingkungan selama kehamilan. 19 Asupan protein dalam penelitian ini tidak berbeda bermakna untuk kedua kelompok IMT tinggi dan rendah ada awal kehamilan; asupan protein ini juga sudah mencukupi kebutuhan menurut berat badan subjek (0,93 g/kgBB), yaitu 0,8-1 g/kgBB. Kecukupan energi dan protein tersebut didasarkan berat badan pada awal kehamilan.…”

Epigenetics, fragile X syndrome and transcriptional therapy

“…Epigenetic changes can be induced by DNA damage [O'Hagan et al, 2008;Tabish et al, 2012] but also by the environment, thus providing a connection between the outer world and DNA, that is, the genetic library where all possible repertoires of molecular responses are stored. For example, food can alter the epigenetics of rats on different diets [Burdge et al, 2011] and changes in DNA methylation may occur as a result of low dietary levels of folate, methionine, or selenium, which can have profound clinical consequences such as neural tube defects, cancer and atherosclerosis [Friso and Choi, 2002;Ulrey et al, 2005].…”

“…of rats on different diets [Burdge et al, 2011] and changes in DNA methylation may occur as a result of low dietary levels of folate, methionine, or selenium, which can have profound clinical consequences such as neural tube defects, cancer and atherosclerosis [Friso and Choi, 2002;Ulrey et al, 2005].…”