Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of Oxtr in Offspring Hippocampus in a Sex-Specific Manner
Abstract
:1. Introduction
2. Results
2.1. Maternal High Fat Diet-Induced Obesity Modulates Expression of Oxtr mRNA in Hippocampus of Male Offspring
2.2. Maternal High Fat Diet-Induced Obesity Alters Histone H3 Acetyl Lysine Binding to the Promoter Region of Oxtr in Hippocampus of Male Offspring
3. Discussion
4. Materials and Methods
4.1. Animal Housing and Maternal Diet
4.2. RNA Extraction
4.3. Quantitative PCR (qPCR)
4.4. ChIP-qPCR
4.5. Statistical Analysis
Supplementary Materials
Author Contributions
Funding
Conflicts of Interest
Abbreviations
ADHD | attention deficit hyperactivity disorder |
ASD | autism spectrum disorders |
Avp | Arginine vasopressin |
Avpr1a | Arginine vasopressin receptor 1A |
ChIP | Chromatin Immunoprecipitation |
GD | Gestational day |
H3K9Ac | Histone 3 Lysine 9 Acetylation |
H3K9me3 | Histone 3 Lysine 9 methylation |
mHFD | Maternal high fat diet |
Oxt | Oxytocin |
Oxtr | Oxytocin receptor |
qPCR | Quantitative PCR |
TSS | Transcription start site |
References
- Heijmans, B.T.; Tobi, E.W.; Stein, A.D.; Putter, H.; Blauw, G.J.; Susser, E.S.; Slagboom, P.E.; Lumey, L.H. Persistent epigenetic differences associated with prenatal exposure to famine in humans. Proc. Natl. Acad. Sci. USA 2008, 105, 17046–17049. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Cooper, W.N.; Khulan, B.; Owens, S.; Elks, C.E.; Seidel, V.; Prentice, A.M.; Belteki, G.; Ong, K.K.; Affara, N.A.; Constancia, M.; et al. DNA methylation profiling at imprinted loci after periconceptional micronutrient supplementation in humans: Results of a pilot randomized controlled trial. FASEB J. 2012, 26, 1782–1790. [Google Scholar] [CrossRef] [PubMed]
- Schack-Nielsen, L.; Michaelsen, K.F.; Gamborg, M.; Mortensen, E.L.; Sorensen, T.I.A. Gestational weight gain in relation to offspring body mass index and obesity from infancy through adulthood. Int. J. Obes. 2010, 34, 67–74. [Google Scholar] [CrossRef] [PubMed]
- Samuelsson, A.M.; Matthews, P.A.; Argenton, M.; Christie, M.R.; McConnell, J.M.; Jansen, E.H.; Piersma, A.H.; Ozanne, S.E.; Twinn, D.F.; Remacle, C.; et al. Diet-induced obesity in female mice leads to offspring hyperphagia, adiposity, hypertension, and insulin resistance: A novel murine model of developmental programming. Hypertension 2008, 51, 383–392. [Google Scholar] [CrossRef] [PubMed]
- Vucetic, Z.; Kimmel, J.; Totoki, K.; Hollenbeck, E.; Reyes, T.M. Maternal high-fat diet alters methylation and gene expression of dopamine and opioid-related genes. Endocrinology 2010, 151, 4756–4764. [Google Scholar] [CrossRef] [PubMed]
- Zheng, J.; Xiao, X.H.; Zhang, Q.; Yu, M.; Xu, J.P.; Wang, Z.X.; Qi, C.J.; Wang, T. Maternal and post-weaning high-fat, high-sucrose diet modulates glucose homeostasis and hypothalamic POMC promoter methylation in mouse offspring. Metab. Brain Dis. 2015, 30, 1129–1137. [Google Scholar] [CrossRef] [PubMed]
- Krakowiak, P.; Walker, C.K.; Bremer, A.A.; Baker, A.S.; Ozonoff, S.; Hansen, R.L.; Hertz-Picciotto, I. Maternal metabolic conditions and risk for autism and other neurodevelopmental disorders. Pediatrics 2012, 129, e1121–e1128. [Google Scholar] [CrossRef]
- Rodriguez, A. Maternal pre-pregnancy obesity and risk for inattention and negative emotionality in children. J. Child Psychol. Psychiatr. Allied Discip. 2010, 51, 134–143. [Google Scholar] [CrossRef]
- Basatemur, E.; Gardiner, J.; Williams, C.; Melhuish, E.; Barnes, J.; Sutcliffe, A. Maternal prepregnancy BMI and child cognition: A longitudinal cohort study. Pediatrics 2013, 131, 56–63. [Google Scholar] [CrossRef]
- Bergmann, S.; Schlesier-Michel, A.; Wendt, V.; Grube, M.; Keitel-Korndorfer, A.; Gausche, R.; von Klitzing, K.; Klein, A.M. Maternal Weight Predicts Children’s Psychosocial Development via Parenting Stress and Emotional Availability. Front. Psychol. 2016, 7, 1156. [Google Scholar] [CrossRef]
- Contu, L.; Hawkes, C.A. A Review of the Impact of Maternal Obesity on the Cognitive Function and Mental Health of the Offspring. Int. J. Mol. Sci. 2017, 18, 1093. [Google Scholar] [CrossRef]
- Glendining, K.A.; Fisher, L.C.; Jasoni, C.L. Maternal high fat diet alters offspring epigenetic regulators, amygdala glutamatergic profile and anxiety. Psychoneuroendocrinology 2018, 96, 132–141. [Google Scholar] [CrossRef] [PubMed]
- Kang, S.S.; Kurti, A.; Fair, D.A.; Fryer, J.D. Dietary intervention rescues maternal obesity induced behavior deficits and neuroinflammation in offspring. J. Neuroinflamm. 2014, 11, 156. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Amir, R.E.; Van den Veyver, I.B.; Wan, M.; Tran, C.Q.; Francke, U.; Zoghbi, H.Y. Rett syndrome is caused by mutations in X-linked MECP2, encoding methyl-CpG-binding protein 2. Nat. Genet. 1999, 23, 185–188. [Google Scholar] [CrossRef] [PubMed]
- Nagarajan, R.P.; Hogart, A.R.; Gwye, Y.; Martin, M.R.; LaSalle, J.M. Reduced MeCP2 Expression is Frequent in Autism Frontal Cortex and Correlates with Aberrant MECP2 Promoter Methylation. Epigenetics-Us 2006, 1, 172–182. [Google Scholar] [CrossRef] [Green Version]
- Saradalekshmi, K.R.; Neetha, N.V.; Sathyan, S.; Nair, I.V.; Nair, C.M.; Banerjee, M. DNA Methyl Transferase (DNMT) Gene Polymorphisms Could Be a Primary Event in Epigenetic Susceptibility to Schizophrenia. PLoS ONE 2014, 9, e98182. [Google Scholar] [CrossRef]
- Gregory, S.G.; Connelly, J.J.; Towers, A.J.; Johnson, J.; Biscocho, D.; Markunas, C.A.; Lintas, C.; Abramson, R.K.; Wright, H.H.; Ellis, P.; et al. Genomic and epigenetic evidence for oxytocin receptor deficiency in autism. BMC Med. 2009, 7, 62. [Google Scholar] [CrossRef]
- Miller, M.; Bales, K.L.; Taylor, S.L.; Yoon, J.; Hostetler, C.M.; Carter, C.S.; Solomon, M. Oxytocin and vasopressin in children and adolescents with autism spectrum disorders: Sex differences and associations with symptoms. Autism Res. Off. J. Int. Soc. Autism Res. 2013, 6, 91–102. [Google Scholar] [CrossRef]
- Rich, M.E.; Caldwell, H.K. A Role for Oxytocin in the Etiology and Treatment of Schizophrenia. Front. Endocrinol. 2015, 6, 90. [Google Scholar] [CrossRef]
- Bodden, C.; van den Hove, D.; Lesch, K.P.; Sachser, N. Impact of varying social experiences during life history on behaviour, gene expression, and vasopressin receptor gene methylation in mice. Sci. Rep. 2017, 7, 8719. [Google Scholar] [CrossRef] [Green Version]
- Kumsta, R.; Hummel, E.; Chen, F.S.; Heinrichs, M. Epigenetic regulation of the oxytocin receptor gene: Implications for behavioral neuroscience. Front. Neurosci. 2013, 7, 83. [Google Scholar] [CrossRef] [PubMed]
- Dogra, S.; Sona, C.; Kumar, A.; Yadav, P.N. Epigenetic regulation of G protein coupled receptor signaling and its implications in psychiatric disorders. Int. J. Biochem. Cell Biol. 2016, 77, 226–239. [Google Scholar] [CrossRef] [PubMed]
- Kim, D.W.; Young, S.L.; Grattan, D.R.; Jasoni, C.L. Obesity during pregnancy disrupts placental morphology, cell proliferation, and inflammation in a sex-specific manner across gestation in the mouse. Biol. Reprod. 2014, 90, 130. [Google Scholar] [CrossRef] [PubMed]
- Kim, D.W.; Glendining, K.A.; Grattan, D.R.; Jasoni, C.L. Maternal obesity in the mouse compromises the blood-brain barrier in the arcuate nucleus of offspring. Endocrinology 2016, 157, 2229–2242. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Kim, D.W.; Glendining, K.A.; Grattan, D.R.; Jasoni, C.L. Maternal obesity leads to increased proliferation and numbers of astrocytes in the developing fetal and neonatal mouse hypothalamus. Int. J. Dev. Neurosci. 2016, 53, 18–25. [Google Scholar] [CrossRef] [PubMed]
- Sanders, T.R.; Glendining, K.A.; Jasoni, C.L. Obesity during pregnancy in the mouse alters the Netrin-1 responsiveness of foetal arcuate nucleus neuropeptide Y neurones. J. Neuroendocrinol. 2017, 29. [Google Scholar] [CrossRef] [PubMed]
- Sanders, T.R.; Kim, D.W.; Glendining, K.A.; Jasoni, C.L. Maternal obesity and IL-6 lead to aberrant developmental gene expression and deregulated neurite growth in the fetal arcuate nucleus. Endocrinology 2014, 155, 2566–2577. [Google Scholar] [CrossRef]
- Li, C.; Guo, S.; Gao, J.; Guo, Y.; Du, E.; Lv, Z.; Zhang, B. Maternal high-zinc diet attenuates intestinal inflammation by reducing DNA methylation and elevating H3K9 acetylation in the A20 promoter of offspring chicks. J. Nutr. Biochem. 2015, 26, 173–183. [Google Scholar] [CrossRef]
- Yang, K.F.; Cai, W.; Xu, J.L.; Shi, W. Maternal high-fat diet programs Wnt genes through histone modification in the liver of neonatal rats. J. Mol. Endocrinol. 2012, 49, 107–114. [Google Scholar] [CrossRef] [Green Version]
- Shahbazian, M.D.; Grunstein, M. Functions of site-specific histone acetylation and deacetylation. Annu. Rev. Biochem. 2007, 76, 75–100. [Google Scholar] [CrossRef]
- Tran, L.; Schulkin, J.; Ligon, C.O.; Greenwood-Van Meerveld, B. Epigenetic modulation of chronic anxiety and pain by histone deacetylation. Mol. Psychiatry 2015, 20, 1219–1231. [Google Scholar] [CrossRef] [PubMed]
- Pfaff, D.W.; Arnold, A.P.; Fahrbach, S.A.; Etgen, A.M.; Rubin, R.T.E. Hormones, Brain, and Behavior; Elsevier Inc.: Amsterdam, The Netherlands, 2002. [Google Scholar]
- Tyzio, R.; Cossart, R.; Khalilov, I.; Minlebaev, M.; Hubner, C.A.; Represa, A.; Ben-Ari, Y.; Khazipov, R. Maternal oxytocin triggers a transient inhibitory switch in GABA signaling in the fetal brain during delivery. Science 2006, 314, 1788–1792. [Google Scholar] [CrossRef] [PubMed]
- Sala, M.; Braida, D.; Lentini, D.; Busnelli, M.; Bulgheroni, E.; Capurro, V.; Finardi, A.; Donzelli, A.; Pattini, L.; Rubino, T.; et al. Pharmacologic Rescue of Impaired Cognitive Flexibility, Social Deficits, Increased Aggression, and Seizure Susceptibility in Oxytocin Receptor Null Mice: A Neurobehavioral Model of Autism. Biol. Psychiatry 2011, 69, 875–882. [Google Scholar] [CrossRef] [PubMed]
- Ripamonti, S.; Ambrozkiewicz, M.C.; Guzzi, F.; Gravati, M.; Biella, G.; Bormuth, I.; Hammer, M.; Tuffy, L.P.; Sigler, A.; Kawabe, H.; et al. Transient oxytocin signaling primes the development and function of excitatory hippocampal neurons. eLife 2017, 6. [Google Scholar] [CrossRef]
- Peleg-Raibstein, D.; Luca, E.; Wolfrum, C. Maternal high-fat diet in mice programs emotional behavior in adulthood. Behav. Brain Res. 2012, 233, 398–404. [Google Scholar] [CrossRef] [PubMed]
- Tozuka, Y.; Wada, E.; Wada, K. Diet-induced obesity in female mice leads to peroxidized lipid accumulations and impairment of hippocampal neurogenesis during the early life of their offspring. FASEB J. 2009, 23, 1920–1934. [Google Scholar] [CrossRef] [PubMed]
- Page, K.C.; Jones, E.K.; Anday, E.K. Maternal and postweaning high-fat diets disturb hippocampal gene expression, learning, and memory function. Am. J. Physiol. Regul. Integr. Comp. Physiol. 2014, 306, R527–R537. [Google Scholar] [CrossRef] [PubMed]
- Elagoz Yuksel, M.; Yuceturk, B.; Karatas, O.F.; Ozen, M.; Dogangun, B. The altered promoter methylation of oxytocin receptor gene in autism. J. Neurogenet. 2016, 30, 280–284. [Google Scholar] [CrossRef]
- LoParo, D.; Waldman, I.D. The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: A meta-analysis. Mol. Psychiatry 2015, 20, 640–646. [Google Scholar] [CrossRef]
- Tyzio, R.; Nardou, R.; Ferrari, D.C.; Tsintsadze, T.; Shahrokhi, A.; Eftekhari, S.; Khalilov, I.; Tsintsadze, V.; Brouchoud, C.; Chazal, G.; et al. Oxytocin-mediated GABA inhibition during delivery attenuates autism pathogenesis in rodent offspring. Science 2014, 343, 675–679. [Google Scholar] [CrossRef]
- Hitti, F.L.; Siegelbaum, S.A. The hippocampal CA2 region is essential for social memory. Nature 2014, 508, 88–92. [Google Scholar] [CrossRef] [Green Version]
- Radwan, B.; Dvorak, D.; Fenton, A.A. Impaired cognitive discrimination and discoordination of coupled theta-gamma oscillations in Fmr1 knockout mice. Neurobiol. Dis. 2016, 88, 125–138. [Google Scholar] [CrossRef]
- Anderson, E.B.; Grossrubatscher, I.; Frank, L. Dynamic Hippocampal Circuits Support Learning- and Memory-Guided Behaviors. Cold Spring Harb. Symp. Quant. Biol. 2014, 79, 51–58. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Tozuka, Y.; Kumon, M.; Wada, E.; Onodera, M.; Mochizuki, H.; Wada, K. Maternal obesity impairs hippocampal BDNF production and spatial learning performance in young mouse offspring. Neurochem. Int. 2010, 57, 235–247. [Google Scholar] [CrossRef]
- Buffington, S.A.; Di Prisco, G.V.; Auchtung, T.A.; Ajami, N.J.; Petrosino, J.F.; Costa-Mattioli, M. Microbial Reconstitution Reverses Maternal Diet-Induced Social and Synaptic Deficits in Offspring. Cell 2016, 165, 1762–1775. [Google Scholar] [CrossRef]
- Edlow, A.G.; Guedj, F.; Pennings, J.L.A.; Sverdlov, D.; Neri, C.; Bianchi, D.W. Males are from Mars, and females are from Venus: Sex-specific fetal brain gene expression signatures in a mouse model of maternal diet-induced obesity. Am. J. Obstet. Gynecol. 2016, 214, 623.e1–623.e10. [Google Scholar] [CrossRef] [PubMed]
- Balint, S.; Czobor, P.; Komlosi, S.; Meszaros, A.; Simon, V.; Bitter, I. Attention deficit hyperactivity disorder (ADHD): Gender- and age-related differences in neurocognition. Psychol. Med. 2009, 39, 1337–1345. [Google Scholar] [CrossRef]
- Fombonne, E. Epidemiology of pervasive developmental disorders. Pediatr. Res. 2009, 65, 591–598. [Google Scholar] [CrossRef] [PubMed]
- Rose, N.R.; Klose, R.J. Understanding the relationship between DNA methylation and histone lysine methylation. BBA-Gene Regul. Mech. 2014, 1839, 1362–1372. [Google Scholar] [CrossRef] [Green Version]
- Kusui, C.; Kimura, T.; Ogita, K.; Nakamura, H.; Matsumura, Y.; Koyama, M.; Azuma, C.; Murata, Y. DNA methylation of the human oxytocin receptor gene promoter regulates tissue-specific gene suppression. Biochem. Biophys. Res. Commun. 2001, 289, 681–686. [Google Scholar] [CrossRef]
- Gonneaud, A.; Gagne, J.M.; Turgeon, N.; Asselin, C. The histone deacetylase Hdac1 regulates inflammatory signalling in intestinal epithelial cells. J. Inflamm. (Lond.) 2014, 11, 43. [Google Scholar] [CrossRef] [PubMed]
- Leus, N.G.J.; Zwinderman, M.R.H.; Dekker, F.J. Histone deacetylase 3 (HDAC 3) as emerging drug target in NF-kappa B-mediated inflammation. Curr. Opin. Chem. Biol. 2016, 33, 160–168. [Google Scholar] [CrossRef] [PubMed]
- Hinkle, S.N.; Schieve, L.A.; Stein, A.D.; Swan, D.W.; Ramakrishnan, U.; Sharma, A.J. Associations between maternal prepregnancy body mass index and child neurodevelopment at 2 years of age. Int. J. Obes. 2012, 36, 1312–1319. [Google Scholar] [CrossRef] [PubMed] [Green Version]
- Jones, P.B.; Rantakallio, P.; Hartikainen, A.L.; Isohanni, M.; Sipila, P. Schizophrenia as a long-term outcome of pregnancy, delivery, and perinatal complications: A 28-year follow-up of the 1966 North Finland general population birth cohort. Am. J. Psychiat. 1998, 155, 355–364. [Google Scholar] [CrossRef] [PubMed]
- Reynolds, L.C.; Inder, T.E.; Neil, J.J.; Pineda, R.G.; Rogers, C.E. Maternal obesity and increased risk for autism and developmental delay among very preterm infants. J. Perinatol. 2014, 34, 688–692. [Google Scholar] [CrossRef] [PubMed]
- Schaefer, C.A.; Brown, A.S.; Wyatt, R.J.; Kline, J.; Begg, M.D.; Bresnahan, M.A.; Susser, E.S. Maternal prepregnant body mass and risk of schizophrenia in adult offspring. Schizophr. Bull. 2000, 26, 275–286. [Google Scholar] [CrossRef] [PubMed]
- Heslehurst, N.; Rankin, J.; Wilkinson, J.R.; Summerbell, C.D. A nationally representative study of maternal obesity in England, UK: Trends in incidence and demographic inequalities in 619 323 births, 1989–2007. Int. J. Obes. 2010, 34, 420–428. [Google Scholar] [CrossRef]
- Gregor, L.; Remington, P.L.; Lindberg, S.; Ehrenthal, D. Prevalence of Pre-pregnancy Obesity, 2011–2014. WMJ Off. Publ. State Med. Soc. Wis. 2016, 115, 228–232. [Google Scholar]
- Glendining, K.A.; Markie, D.; Gardner, R.J.; Franz, E.A.; Robertson, S.P.; Jasoni, C.L. A novel role for the DNA repair gene Rad51 in Netrin-1 signalling. Sci. Rep. 2017, 7, 39823. [Google Scholar] [CrossRef] [Green Version]
- Pfaffl, M.W. A new mathematical model for relative quantification in real-time RT-PCR. Nucleic Acids Res. 2001, 29, e45. [Google Scholar] [CrossRef]
© 2019 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/).
Share and Cite
Glendining, K.A.; Jasoni, C.L. Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of Oxtr in Offspring Hippocampus in a Sex-Specific Manner. Int. J. Mol. Sci. 2019, 20, 329. https://doi.org/10.3390/ijms20020329
Glendining KA, Jasoni CL. Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of Oxtr in Offspring Hippocampus in a Sex-Specific Manner. International Journal of Molecular Sciences. 2019; 20(2):329. https://doi.org/10.3390/ijms20020329
Chicago/Turabian StyleGlendining, Kelly A., and Christine L. Jasoni. 2019. "Maternal High Fat Diet-Induced Obesity Modifies Histone Binding and Expression of Oxtr in Offspring Hippocampus in a Sex-Specific Manner" International Journal of Molecular Sciences 20, no. 2: 329. https://doi.org/10.3390/ijms20020329