scholarly journals Developmental Timing of the Effects of Maternal Care on Gene Expression and Epigenetic Regulation of Hormone Receptor Levels in Female Rats

Endocrinology ◽  
2013 ◽  
Vol 154 (11) ◽  
pp. 4340-4351 ◽  
Author(s):  
Catherine Jensen Peña ◽  
Y. Dana Neugut ◽  
Frances A. Champagne
Keyword(s):  
Dna Methylation ◽  
Maternal Behavior ◽  
Maternal Care ◽  
Female Offspring ◽  
Oxytocin Receptor ◽  
Developmental Timing ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Histone 3 ◽  
Cross Fostering

Maternal care experienced during postnatal development has enduring effects on neuroendocrine function and behavior. Previous studies in rats have illustrated the effect of maternal licking/grooming (LG) on hormone receptors and maternal behavior of adult female offspring associated with altered DNA methylation. However, the developmental timing of these effects, which provide insight into the cellular and molecular pathways through which early experience alters later behavior, had not been explored. Here, we demonstrate the developmental emergence of these outcomes and use cross-fostering to identify sensitive periods for these effects. Estrogen receptor (ER)α and ERβ mRNA levels within the medial preoptic area (MPOA) of the hypothalamus were increased by postnatal day (PN)21 in female offspring of high LG dams; LG-associated increases in oxytocin receptor mRNA levels were observed beyond the weaning period. Quantification of ERα-immunoreactivity indicated a high degree of neuroanatomical specificity of LG effects within the MPOA that were observed by PN6. Reduced DNA methylation and histone 3 lysine 9 tri-methylation and increased histone 3 lysine 4 tri-methylation at the ERα gene promoter (Esr1) were detected at PN21 in high LG female offspring. Latency to engage in maternal behavior toward donor pups was significantly shorter among high LG females. Cross-fostering revealed that maternal sensitization and MPOA ERα levels are sensitive to maternal care experienced before but not after PN10. Differential windows of plasticity were identified for ERβ and oxytocin receptor mRNA levels. These studies contribute significantly to our understanding of the molecular, neurobiological, and behavioral pathways through which variation in maternal behavior is transmitted from one generation to the next.

scholarly journals Oxytocin Receptor Gene Polymorphism in Lactating Dogs

Animals ◽  
2021 ◽  
Vol 11 (11) ◽  
pp. 3099
Author(s):  
Asahi Ogi ◽  
Valentina Naef ◽  
Filippo Maria Santorelli ◽  
Chiara Mariti ◽  
Angelo Gazzano
Keyword(s):  
Social Behavior ◽  
Maternal Behavior ◽  
Maternal Care ◽  
Receptor Gene ◽  
Oxytocin Receptor ◽  
Single Nucleotide ◽  
Oxytocin Receptor Gene ◽  
Receptor Gene Polymorphism ◽  
Polymorphic Variants ◽  
Evolution Of Mammals

Genetic variations in the oxytocinergic system, known to regulate social behavior throughout the evolution of mammals, are believed to account for differences in mammalian social behavior. Particularly, polymorphic variants of the oxytocin receptor (OXTR) gene have been associated with behavioral variations in both humans and dogs. In this study, we offered evidence of the correlation between levels of salivary oxytocin (sOXT), maternal behavior and a single-nucleotide gene variant in OXTR (rs8679684) in nineteen lactating Labrador Retriever dogs. Carriers of at least one copy of the minor A allele showed higher levels of sOXT and maternal care in comparison with the homozygous T allele carriers. Considering the relevance of mother care in newborn development, these findings could help us to better understand the possible impact of variants in the OXTR gene in selecting dams.

Effects of Mixtures of Polychlorinated Biphenyls, Methylmercury, and Organochlorine Pesticides on Hepatic DNA Methylation in Prepubertal Female Sprague-Dawley Rats

2009 ◽  
Vol 28 (4) ◽  
pp. 294-307 ◽  
Author(s):  
Daniel Desaulniers ◽  
Gong-hua Xiao ◽  
Hong Lian ◽  
Yong-Lai Feng ◽  
Jiping Zhu ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Polychlorinated Biphenyls ◽  
Organochlorine Pesticides ◽  
Dna Methyltransferase ◽  
Female Offspring ◽  
High Dose ◽  
Mrna Levels ◽  
Postnatal Exposure ◽  
Sprague Dawley ◽  
Pregnant Rats

DNA methylation is one of the epigenetic mechanisms that regulates gene expression, chromosome structure, and stability. Our objective was to determine whether the DNA methylation system could be a target following in utero and postnatal exposure to human blood contaminants. Pregnant rats were dosed daily from gestation day 1 until postnatal day 21 with 2 dose levels of either organochlorine pesticides (OCP; 0.019 or 1.9 mg/kg/day), methylmercury chloride (MeHg; 0.02 or 2 mg/kg/day), polychlorinated biphenyls (PCBs; 0.011 or 1.1 mg/kg/day), or a mixture (Mix; 0.05, or 5 mg/kg/day) including all 3 groups of chemicals. Livers from 1 female offspring per litter were collected at postnatal day 29. Hepatic analysis revealed that the mRNA abundance for DNA methyltransferase (DNMT)-1, -3a, and -3b were significantly reduced by the high dose of PCB, that the high dose of MeHg also reduced mRNA levels for DNMT-1, and -3b, but that OCP had no significant effects compared with control. The high dose of PCB and Mix reduced the abundance of the universal methyl donor S-adenosylmethionine, and Mix also reduced global genome DNA methylation (5-methyl-deoxycytidine/5-methyl-deoxycytidine + deoxycytidine). The latter is consistent with pyrosequencing methylation analysis, revealing that the high-dose groups (except OCP) generally decreased the methylation of CpG sites (position -63 to -29) in the promoter of the tumor suppressor gene p16INK4a. Overall, these hepatic results suggest that the DNA methylation system can be affected by exposure to high doses of blood contaminants, and that OCP is the least potent chemical group from the investigated mixtures.

T56. DNA Methylation of the Oxytocin Receptor Changes During Infancy and is Impacted by Maternal Behavior

2019 ◽  
Vol 85 (10) ◽  
pp. S150
Author(s):  
Kathleen Krol ◽  
Robert Moulder ◽  
Travis Lillard ◽  
Tobias Grossmann ◽  
Jessica Connelly
Keyword(s):  
Dna Methylation ◽  
Maternal Behavior ◽  
Oxytocin Receptor

Uteroplacental insufficiency affects epigenetic determinants of chromatin structure in brains of neonatal and juvenile IUGR rats

2006 ◽  
Vol 25 (1) ◽  
pp. 16-28 ◽  
Author(s):  
X. Ke ◽  
Q. Lei ◽  
S. J. James ◽  
S. L. Kelleher ◽  
S. Melnyk ◽  
...  
Keyword(s):  
Dna Methylation ◽  
White Matter ◽  
Breast Milk ◽  
Histone Acetylation ◽  
Chromatin Structure ◽  
Male Rats ◽  
Caloric Content ◽  
Periventricular White Matter ◽  
Mrna Levels ◽  
Histone 3

Intrauterine growth retardation (IUGR) increases the risk of neuroendocrine reprogramming. In the rat, IUGR leads to persistent changes in cerebral mRNA levels. This suggests lasting alterations in IUGR cerebral transcriptional regulation, which may result from changes in chromatin structure. Candidate nutritional triggers for these changes include altered cerebral zinc and one-carbon metabolite levels. We hypothesized that IUGR affects cerebral chromatin structure in neonatal and postnatal rat brains. Rats were rendered IUGR by bilateral uterine artery ligation; controls (Con) underwent sham surgery. At day of life 0 (d0), we measured cerebral DNA methylation, histone acetylation, expression of chromatin-affecting enzymes, and cerebral levels of one-carbon metabolites and zinc. At day of life 21 (d21), we measured cerebral DNA methylation and histone acetylation, as well as the caloric content of Con and IUGR rat breast milk. At d0, IUGR significantly decreased genome-wide and CpG island methylation, as well as increased histone 3 lysine 9 (H3/K9) and histone 3 lysine 14 (H3/K14) acetylation in the hippocampus and periventricular white matter, respectively. IUGR also decreased expression of the chromatin-affecting enzymes DNA methyltransferase 1 (DNMT1), methyl-CpG binding protein 2 (MeCP2), and histone deacetylase (HDAC)1 in association with increased cerebral levels of zinc. In d21 female IUGR rats, cerebral CpG DNA methylation remained lower, whereas H3/K9 and H3/K14 hyperacetylation persisted in hippocampus and white matter, respectively. In d21 male rats, IUGR decreased acetylation of H3/K9 and H3/K14 in these respective regions compared with controls. Despite these differences, caloric, fat, and protein content were similar in breast milk from Con and IUGR dams. We conclude that IUGR results in postnatal changes in cerebral chromatin structure and that these changes are sex specific.

scholarly journals Significant association of interleukin 10 receptor mRNA levels with renal cell carcinoma metastasis

2008 ◽  
Vol 29 (1) ◽  
pp. 19-25 ◽  
Author(s):  
Hideyuki ABE ◽  
Tomonori YAMANISHI ◽  
Tomoko MASHIDORI ◽  
Kyoko ARAI ◽  
Takao KAMAI
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Interleukin 10 ◽  
Mrna Levels ◽  
Receptor Mrna ◽  
Renal Cell Carcinoma Metastasis ◽  
Carcinoma Metastasis

scholarly journals Postnatal Smoke Exposure Further Increases the Hepatic Nicotine Metabolism in Prenatally Smoke Exposed Male Offspring and Is Linked with Aberrant Cyp2a5 Methylation

2020 ◽  
Vol 22 (1) ◽  
pp. 164
Author(s):  
Khosbayar Lkhagvadorj ◽  
Zhijun Zeng ◽  
Karolin F. Meyer ◽  
Laura P. Verweij ◽  
Wierd Kooistra ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Mrna Expression ◽  
Nicotine Dependence ◽  
Susceptibility Gene ◽  
Smoke Exposure ◽  
Adverse Outcomes ◽  
Male Offspring ◽  
Adult Offspring ◽  
Mrna Levels ◽  
Nicotine Metabolism

Prenatal smoke exposure (PreSE) is a risk factor for nicotine dependence, which is further enhanced by postnatal smoke exposure (PostSE). One susceptibility gene to nicotine dependence is Cytochrome P450 (CYP) 2A6, an enzyme responsible for the conversion of nicotine to cotinine in the liver. Higher CYP2A6 activity is associated with nicotine dependence and could be regulated through DNA methylation. In this study we investigated whether PostSE further impaired PreSE-induced effects on nicotine metabolism, along with Cyp2a5, orthologue of CYP2A6, mRNA expression and DNA methylation. Using a mouse model where prenatally smoke-exposed adult offspring were exposed to cigarette smoke for 3 months, enzyme activity, mRNA levels, and promoter methylation of hepatic Cyp2a5 were evaluated. We found that in male offspring, PostSE increased PreSE-induced cotinine levels and Cyp2a5 mRNA expression. In addition, both PostSE and PreSE changed Cyp2a5 DNA methylation in male groups. PreSE however decreased cotinine levels whereas it had no effect on Cyp2a5 mRNA expression or methylation. These adverse outcomes of PreSE and PostSE were most prominent in males. When considered in the context of the human health aspects, the combined effect of prenatal and adolescent smoke exposure could lead to an accelerated risk for nicotine dependence later in life.

scholarly journals Creatine Alleviates Doxorubicin-Induced Liver Damage by Inhibiting Liver Fibrosis, Inflammation, Oxidative Stress, and Cellular Senescence

Nutrients ◽  
2020 ◽  
Vol 13 (1) ◽  
pp. 41
Author(s):  
Nouf Aljobaily ◽  
Michael J. Viereckl ◽  
David S. Hydock ◽  
Hend Aljobaily ◽  
Tsung-Yen Wu ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Dna Methylation ◽  
Body Weight ◽  
Liver Fibrosis ◽  
Liver Damage ◽  
Cellular Senescence ◽  
Weight Ratio ◽  
Mrna Levels ◽  
Body Weight Ratio ◽  
Chromosomal Stability

Background: Treatment with the chemotherapy drug doxorubicin (DOX) may lead to toxicities that affect non-cancer cells including the liver. Supplementing the diet with creatine (Cr) has been suggested as a potential intervention to minimize DOX-induced side effects, but its effect in alleviating DOX-induced hepatoxicity is currently unknown. Therefore, we aimed to examine the effects of Cr supplementation on DOX-induced liver damage. Methods: Male Sprague-Dawley rats were fed a diet supplemented with 2% Cr for four weeks, 4% Cr for one week followed by 2% Cr for three more weeks, or control diet for four weeks. Animals then received either a bolus i.p. injection of DOX (15 mg/kg) or saline as a placebo. Animals were then sacrificed five days-post injection and markers of hepatoxicity were analyzed using the liver-to-body weight ratio, aspartate transaminase (AST)-to- alanine aminotransferase (ALT) ratio, alkaline phosphatase (ALP), lipemia, and T-Bilirubin. In addition, hematoxylin and eosin (H&E) staining, Picro-Sirius Red staining, and immunofluorescence staining for CD45, 8-OHdG, and β-galactosidase were performed to evaluate liver morphology, fibrosis, inflammation, oxidative stress, and cellular senescence, respectively. The mRNA levels for biomarkers of liver fibrosis, inflammation, oxidative stress, and senescence-related genes were measured in liver tissues. Chromosomal stability was evaluated using global DNA methylation ELISA. Results: The ALT/AST ratio and liver to body weight ratio tended to increase in the DOX group, and Cr supplementation tended to attenuate this increase. Furthermore, elevated levels of liver fibrosis, inflammation, oxidative stress, and senescence were observed with DOX treatment, and Cr supplementation prior to DOX treatment ameliorated this hepatoxicity. Moreover, DOX treatment resulted in chromosomal instability (i.e., altered DNA methylation profile), and Cr supplementation showed a tendency to restore chromosomal stability with DOX treatment. Conclusion: The data suggest that Cr protected against DOX-induced hepatotoxicity by attenuating fibrosis, inflammation, oxidative stress, and senescence.

scholarly journals Urate-induced epigenetic modifications in myeloid cells

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
M. Badii ◽  
O. I. Gaal ◽  
M. C. Cleophas ◽  
V. Klück ◽  
R. Davar ◽  
...  
Keyword(s):  
Dna Methylation ◽  
Whole Blood ◽  
Mononuclear Cells ◽  
Human Peripheral Blood ◽  
Myeloid Cells ◽  
Cytokine Signaling ◽  
Human Monocytes ◽  
Methylation Array ◽  
Histone 3 ◽  
Msu Crystals

Abstract Objectives Hyperuricemia is a metabolic condition central to gout pathogenesis. Urate exposure primes human monocytes towards a higher capacity to produce and release IL-1β. In this study, we assessed the epigenetic processes associated to urate-mediated hyper-responsiveness. Methods Freshly isolated human peripheral blood mononuclear cells or enriched monocytes were pre-treated with solubilized urate and stimulated with LPS with or without monosodium urate (MSU) crystals. Cytokine production was determined by ELISA. Histone epigenetic marks were assessed by sequencing immunoprecipitated chromatin. Mice were injected intraarticularly with MSU crystals and palmitate after inhibition of uricase and urate administration in the presence or absence of methylthioadenosine. DNA methylation was assessed by methylation array in whole blood of 76 participants with normouricemia or hyperuricemia. Results High concentrations of urate enhanced the inflammatory response in vitro in human cells and in vivo in mice, and broad-spectrum methylation inhibitors reversed this effect. Assessment of histone 3 lysine 4 trimethylation (H3K4me3) and histone 3 lysine 27 acetylation (H3K27ac) revealed differences in urate-primed monocytes compared to controls. Differentially methylated regions (e.g. HLA-G, IFITM3, PRKAB2) were found in people with hyperuricemia compared to normouricemia in genes relevant for inflammatory cytokine signaling. Conclusion Urate alters the epigenetic landscape in selected human monocytes or whole blood of people with hyperuricemia compared to normouricemia. Both histone modifications and DNA methylation show differences depending on urate exposure. Subject to replication and validation, epigenetic changes in myeloid cells may be a therapeutic target in gout.

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