scholarly journals Genetic, epigenetic, and environmental factors controlling oxytocin receptor gene expression

2021 ◽  
Vol 13 (1) ◽  
Author(s):  
Joshua S. Danoff ◽  
Kelly L. Wroblewski ◽  
Andrew J. Graves ◽  
Graham C. Quinn ◽  
Allison M. Perkeybile ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Receptor Gene ◽  
Oxytocin Receptor ◽  
Prairie Vole ◽  
Alternative Transcript ◽  
Prairie Voles ◽  
Oxytocin Receptor Gene ◽  
Cpg Sites ◽  
The Brain

Abstract Background The neuropeptide oxytocin regulates mammalian social behavior. Disruptions in oxytocin signaling are a feature of many psychopathologies. One commonly studied biomarker for oxytocin involvement in psychiatric diseases is DNA methylation at the oxytocin receptor gene (OXTR). Such studies focus on DNA methylation in two regions of OXTR, exon 3 and a region termed MT2 which overlaps exon 1 and intron 1. However, the relative contribution of exon 3 and MT2 in regulating OXTR gene expression in the brain is currently unknown. Results Here, we use the prairie vole as a translational animal model to investigate genetic, epigenetic, and environmental factors affecting Oxtr gene expression in a region of the brain that has been shown to drive Oxtr related behavior in the vole, the nucleus accumbens. We show that the genetic structure of Oxtr in prairie voles resembles human OXTR. We then studied the effects of early life experience on DNA methylation in two regions of a CpG island surrounding the Oxtr promoter: MT2 and exon 3. We show that early nurture in the form of parental care results in DNA hypomethylation of Oxtr in both MT2 and exon 3, but only DNA methylation in MT2 is associated with Oxtr gene expression. Network analyses indicate that CpG sites in the 3′ portion of MT2 are most highly associated with Oxtr gene expression. We also identify two novel SNPs in exon 3 of Oxtr in prairie voles and a novel alternative transcript originating from the third intron of the gene. Expression of the novel alternative transcript is associated with genotype at SNP KLW2. Conclusions These results identify putative regulatory features of Oxtr in prairie voles which inform future studies examining OXTR in human social behaviors and disorders. These studies indicate that in prairie voles, DNA methylation in MT2, particularly in the 3′ portion, is more predictive of Oxtr gene expression than DNA methylation in exon 3. Similarly, in human temporal cortex, we find that DNA methylation in the 3′ portion of MT2 is associated with OXTR expression. Together, these results suggest that among the CpG sites studied, DNA methylation of MT2 may be the most reliable indicator of OXTR gene expression. We also identify novel features of prairie vole Oxtr, including SNPs and an alternative transcript, which further develop the prairie vole as a translational model for studies of OXTR.

scholarly journals Variation in DNA methylation of the oxytocin receptor gene predicts children's resilience to prenatal stress

2017 ◽  
Vol 29 (5) ◽  
pp. 1663-1674 ◽  
Author(s):  
Izabela Milaniak ◽  
Charlotte A. M. Cecil ◽  
Edward D. Barker ◽  
Caroline L. Relton ◽  
Tom R. Gaunt ◽  
...  
Keyword(s):  
Gene Expression ◽  
Dna Methylation ◽  
Conduct Problems ◽  
Middle Childhood ◽  
Receptor Gene ◽  
Conduct Problem ◽  
Oxytocin Receptor ◽  
Future Research ◽  
Oxytocin Receptor Gene ◽  
Wide Range

AbstractEmerging research in epigenetics has shown that there is variability in how environmental exposures “get under the skin” through mechanisms like DNA methylation to influence gene expression that may lead to differential adaptations to stress. This is the first study to examine prospectively the relationship between DNA methylation at birth and resilience to prenatal environmental stressors in several domains (conduct, hyperactivity, emotional problems, and global symptomatology) in middle childhood. We focused on DNA methylation in the vicinity of the oxytocin receptor (OXTR) gene as it has been previously associated with impairments in social–cognitive processes that may underlie a wide range of childhood psychopathology. Participants were 91 youth exposed to pre- and postnatal adversity with established conduct problem trajectories drawn from the Avon Longitudinal Study of Parents and Children. Consistent with our hypothesis, OXTR DNA methylation was predictive of resilience in the conduct problems domain in middle childhood. DNA methylation profiles did not predict resilience in domains of emotional, hyperactivity, and global symptomatology, suggesting a potential role for OXTR in the development of conduct problems in particular. However, individuals who were resilient to conduct problems were also broadly resilient across multiple domains. Therefore, future research should elucidate the biological pathways between OXTR DNA methylation and gene expression and its relation to impairments in social behavior.

scholarly journals Polychlorinated biphenyl exposure alters oxytocin receptor gene expression and maternal behavior in rat model

2015 ◽  
Vol 3 (1) ◽  
pp. e979681 ◽  
Author(s):  
E Nicole Dover ◽  
David E Mankin ◽  
Howard C Cromwell ◽  
Vipaporn Phuntumart ◽  
Lee A Meserve
Keyword(s):  
Gene Expression ◽  
Rat Model ◽  
Maternal Behavior ◽  
Polychlorinated Biphenyl ◽  
Receptor Gene ◽  
Oxytocin Receptor ◽  
Oxytocin Receptor Gene ◽  
Receptor Gene Expression

scholarly journals Maternal blood and amnionic oxytocin receptor gene expression and serum oxytocin levels in preterm birth: a case control study

2020 ◽  
Author(s):  
KUMARI ANUKRITI ◽  
KIRAN GULERIA ◽  
VIPIN TYAGI ◽  
AMITA SUNEJA ◽  
BASU DEV BANERJEE
Keyword(s):  
Gene Expression ◽  
Preterm Birth ◽  
Quantitative Polymerase Chain Reaction ◽  
Receptor Gene ◽  
Active Phase ◽  
Maternal Blood ◽  
Oxytocin Receptor ◽  
Maternal Serum ◽  
Oxytocin Receptor Gene ◽  
Gene Expression Studies

BACKGROUND: The oxytocin (OXT)-oxytocin receptor (OXTR) system provides promising candidate gene for studies of genetic contributions to prematurity. OBJECTIVE: Quantification and comparison of oxytocin receptor (OXTR) gene expression and serum OXT levels in the blood and amnion of women delivering preterm and evaluation of the correlation between OXTR gene expression in blood and amnion with serum OXT levels in them. METHODS: 70 pregnant women in spontaneous labor delivering vaginally preterm i.e < 37 weeks and equal number of matched controls delivering spontaneously at term (37-42 weeks) were recruited. Maternal serum OXT levels taken in active stage of labor (i.e 4 cm cervical dilatation) were quantified by ELISA. Gene expression studies in the maternal blood and amnion were done by using real time quantitative polymerase chain reaction (RT-qPCR). RESULTS: The mean serum OXT level in PTL was 48.56 +- 6.97 pg/ml; significantly higher than in controls (43.00 +- 3.96 pg/ml), p<0.001. OXTR gene expression both in maternal blood (2.5 times) and amnion (3.5 times) were significantly higher in PTL. A significant positive correlation was observed between serum OXT levels and OXTR gene expression in amnion (r = -0.190, p = 0.025). CONCLUSIONS: The serum OXT levels and OXTR gene expression in amnion surge significantly in active phase of PTL. Thus, amnion probably links OXT-PTGs autocrine paracrine circuit to facilitate PTL. Future studies are needed to devise better OXTR receptor antagonists preferably acting on amnionic OXTRs to prevent PTL. KEYWORDS: Preterm birth, Preterm labor, Oxytocin, Oxytocin receptor, Placenta, Amnion

scholarly journals Estrogen Regulates Transcription of the Ovine Oxytocin Receptor Gene through GC-Rich SP1 Promoter Elements

Endocrinology ◽  
2006 ◽  
Vol 147 (2) ◽  
pp. 899-911 ◽  
Author(s):  
JoAnn G. W. Fleming ◽  
Thomas E. Spencer ◽  
Stephen H. Safe ◽  
Fuller W. Bazer
Keyword(s):  
Gene Expression ◽  
Progesterone Receptor ◽  
Gene Transcription ◽  
Binding Sites ◽  
Promoter Activity ◽  
Receptor Gene ◽  
Prostaglandin F2α ◽  
Oxytocin Receptor ◽  
Oxytocin Receptor Gene ◽  
Esr1 Gene

Establishment of pregnancy in ruminants results from paracrine signaling by interferon τ (IFNT) from the conceptus to uterine endometrial luminal epithelia (LE) that prevents release of luteolytic prostaglandin F2α pulses. In cyclic and pregnant ewes, progesterone down-regulates progesterone receptor (PGR) gene expression in LE. In cyclic ewes, loss of PGR allows for increases in estrogen receptor α (ESR1) and then oxytocin receptor (OXTR) gene expression followed by oxytocin-induced prostaglandin F2α pulses. In pregnant ewes, IFNT inhibits transcription of the ESR1 gene, which presumably inhibits OXTR gene transcription. Alternatively, IFNT may directly inhibit OXTR gene transcription. The 5′ promoter/enhancer region of the ovine OXTR gene was cloned and found to contain predicted binding sites for activator protein 1, SP1, and PGR, but not for ESR1. Deletion analysis showed that the basal promoter activity was dependent on the region from −144 to −4 bp that contained only SP1 sites. IFNT did not affect activity of the OXTR promoter. In cells transfected with ESR1, E2, and ICI 182,780 increased promoter activity due to GC-rich SP1 binding sites at positions −104 and −64. Mutation analyses showed that the proximal SP1 sites mediated ESR1 action as well as basal activity of the promoter. In response to progesterone, progesterone receptor B also increased OXTR promoter activity. SP1 protein was constitutively expressed and abundant in the LE of the ovine uterus. These results support the hypothesis that the antiluteolytic effects of IFNT are mediated by direct inhibition or silencing of ESR1 gene transcription, thereby precluding ESR1/SP1 from stimulating OXTR gene transcription.

The role of the endometrial oxytocin receptor in determining the length of the sterile oestrous cycle and ensuring maintenance of luteal function in early pregnancy in ruminants

1994 ◽  
Vol 344 (1309) ◽  
pp. 291-304 ◽  
Keyword(s):  
Gene Expression ◽  
Molecular Mechanisms ◽  
Transmembrane Domain ◽  
Receptor Gene ◽  
Oxytocin Receptor ◽  
Oestrous Cycle ◽  
High Rate ◽  
Endocrine Function ◽  
Oxytocin Receptor Gene ◽  
Receptor Gene Expression

The oxytocin receptor, a seven transmembrane domain, G protein-linked receptor molecule, plays a central role in determining the endocrine function of the ruminant uterine endometrium. During non- pregnant cycles the control of this molecule by circulating steroid hormones leads to regression of the corpora lutea. The kinetics of the mechanisms involved determine the time at which luteolysis occurs, and therefore the length of the oestrous cycle. In pregnancy, secretions of the trophoblast block endometrial oxytocin receptor gene expression and lead to luteal maintenance. An understanding of the molecular mechanisms involved in the steroidal control of oxytocin receptor gene expression will provide an explanation for the relative constancy of oestrous cycle lengths in non-pregnant animals. Unravelling the way in which trophoblast products block expression of the oxytocin receptor gene will lead to a better understanding of the reasons for the high rate of embryonic loss in domestic ruminants.

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