Nutritional Programming of Accelerated Puberty in Heifers: Alterations in DNA Methylation in the Arcuate Nucleus

• Published in: Biology of reproduction Vol. 96; no. 1; pp. 174 - 184
• Main Authors: Alves, Bruna R. C, Cardoso, Rodolfo C, Doan, Ryan, Zhang, Youwen, Dindot, Scott V, Williams, Gary L, Amstalden, Marcel
• Format: Journal Article
• Language: English
• Published: United States Society for the Study of Reproduction 01-01-2017; Oxford University Press
• Subjects: Age; Animals; Arcuate Nucleus of Hypothalamus - metabolism; Cattle; Deoxyribonucleic acid; DNA; DNA Methylation; epigenetics; Female; Gene Expression; GHR; HMGA2; hypothalamus; nutrition; Puberty; Sexual Maturation; Weight Gain; GHR; HMGA2; nutrition; puberty; epigenetics; hypothalamus
• ISSN: 0006-3363; 1529-7268
• DOI: 10.1095/biolreprod.116.144741

High rates of body weight gain during the juvenile period appear to program molecular events within the hypothalamus, leading to advancement of puberty. Methylation of DNA, an epigenetic mechanism that controls gene expression, is associated with metabolic programming events and is proposed to play a role in the pubertal process. In this study, DNA methylation was assessed in genomic DNA obtained from the arcuate nucleus (ARC) of juvenile heifers fed to gain body weight at low (0.5 kg/d; low-gain, LG, n = 4) or high (1 kg/d; high-gain, HG, n = 4) rates from 4.5 to 8.5 mo of age (earliest puberty expected at 9 mo of age in HG heifers). Using a customdesigned oligonucleotide array targeted to imprinted genes and genes associated with nutritional inputs and the control of puberty, a comparative-genomic-hybridization array was used to identify differentially methylated regions between LG and HG heifers. Differential methylation of genomic regions associated with alteredmRNA expression was observed for genes whose activity has been reported to be involved in the modulation of growth and metabolism (GHR) and puberty (HMGA2). Hence, increased rates of body weight gain during the juvenile period alter the methylation pattern of genomic DNA obtained from the ARC and these changes may be involved in programming the age at puberty in heifers. Summary Sentence Increased rates of body weight gain during the juvenile period alter the methylation pattern of genomic DNA obtained from the ARC and these changesmay be involved in programming the age at puberty in heifers.