Affinage

OXTR

Oxytocin receptor · UniProt P30559

Length
389 aa
Mass
42.8 kDa
Annotated
2026-04-29
100 papers in source corpus 17 papers cited in narrative 17 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

OXTR is a G protein-coupled receptor for oxytocin that transduces signals through multiple intracellular cascades—including Gαq/CDC37/ERK5, ERK/STAT3, and nNOS/NO/KATP pathways—to regulate uterine contractility, visceral afferent sensitivity, microglial activation, and cancer-associated fibroblast invasion (PMID:36045118, PMID:37648002, PMID:25346204, PMID:22999795). In the brain, OXTR-expressing neurons form discrete circuits—lateral septum to hippocampal CA1 for social memory and septal GABAergic projections to the horizontal diagonal band of Broca for anxiety modulation—with chemogenetic activation of lateral septum OXTR neurons rescuing social memory deficits in two independent autism spectrum disorder mouse models (PMID:33335150, PMID:34489531, PMID:33092784). OXTR expression is subject to multilayered epigenetic control: TET1-mediated DNA demethylation maintains Oxtr transcription in the brain, histone H3K9 acetylation marks at the Oxtr promoter confer sex-specific regulation, and progesterone receptor isoform B suppresses Oxtr through an Oxtr–Plcl2–Trpc3 axis to maintain uterine quiescence (PMID:30518695, PMID:30650536, PMID:33707208). Cis-regulatory variants including rs237895 exhibit allelic expression imbalance in human amygdala, indicating genetically encoded differences in OXTR output in behaviorally relevant brain regions (PMID:20303388).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2009 Medium

    The question of whether OXTR operates outside classic reproductive and central circuits was addressed by demonstrating OTR expression in enteric neurons and intestinal epithelium, expanding OXTR's functional territory to the enteric nervous system.

    Evidence RT-PCR, immunofluorescence co-localization with neural marker Hu, and immunoelectron microscopy in mouse postnatal myenteric plexus

    PMID:19003903

    Open questions at the time
    • Functional consequence of OTR at enterocyte adherens junctions not tested
    • No loss-of-function study in enteric neurons
  2. 2010 Medium

    Whether common OXTR variants have cis-regulatory effects on gene expression was addressed by identifying allelic expression imbalance at rs237895 in human amygdala, establishing that genetic variation can directly modulate OXTR output in behaviorally relevant tissue.

    Evidence Allelic expression imbalance assay in human lymphoblast cell lines and amygdala tissue

    PMID:20303388

    Open questions at the time
    • Causal variant not pinpointed
    • Functional consequence of differential OXTR expression from these alleles not tested
  3. 2012 Medium

    Whether OXTR expression is epigenetically modifiable was demonstrated by showing that histone deacetylase inhibition suppresses OTR protein in myometrial smooth muscle cells, linking OXTR to histone acetylation-dependent regulation and uterine contractility.

    Evidence Western blot and contractility assay with TSA and andrographolide treatment of cultured MSMCs from adenomyosis patients

    PMID:22999795

    Open questions at the time
    • Specific histone marks and genomic loci not identified
    • No in vivo validation of HDAC inhibitor effects on OXTR
  4. 2014 High

    How OXTR modulates visceral sensory signaling was resolved by defining an OTR/nNOS/NO/KATP pathway through which oxytocin suppresses mesenteric afferent firing, establishing a complete signaling cascade from receptor to effector channel.

    Evidence In vitro mesenteric afferent discharge recording with sequential pharmacological blockade of NOS and KATP channels, plus immunofluorescence co-localization of OTR and nNOS

    PMID:25346204

    Open questions at the time
    • Pathway not tested in vivo
    • Whether this cascade operates in other OXTR-expressing peripheral neurons is unknown
  5. 2018 High

    How OXTR expression is maintained in the brain was established by showing that TET1 prevents CpG island hypermethylation at the Oxtr locus; loss of TET1 reduces Oxtr mRNA isoforms and impairs maternal behavior and synaptic oxytocin responsiveness.

    Evidence Tet1 exon 4-deleted mice (CRISPR/Cas9), bisulfite sequencing, RT-PCR, behavioral assays, and synaptic electrophysiology

    PMID:30518695

    Open questions at the time
    • Whether TET1 acts directly at Oxtr or via intermediate demethylation targets is not resolved
    • Rescue by Oxtr re-expression not performed
  6. 2019 Medium

    Whether OXTR is subject to sex-specific epigenetic regulation was addressed by demonstrating increased H3K9Ac at the Oxtr promoter in male but not female offspring hippocampus following maternal high-fat diet, revealing a sex-dimorphic histone-based mechanism.

    Evidence ChIP for H3K9Ac at Oxtr TSS and RT-PCR in sex-stratified offspring hippocampi from obese dams

    PMID:30650536

    Open questions at the time
    • Causal link between H3K9Ac enrichment and Oxtr mRNA increase not established by loss-of-function
    • Downstream behavioral consequences not measured
  7. 2020 High

    The circuit-level function of brain OXTR was established by showing that chemogenetic activation of OXTR-expressing lateral septum neurons, which project to hippocampal CA1, rescues social memory deficits in two independent ASD mouse models.

    Evidence hM3Dq DREADD activation in OXTR+ LS neurons, three-chamber and single-field social memory tests, anterograde tracing in VPA-exposed and Nl3R451C knock-in mice

    PMID:33335150

    Open questions at the time
    • Molecular mechanism by which OXTR+ LS→CA1 projection encodes social memory is unknown
    • Whether endogenous oxytocin release onto these neurons is necessary for normal social memory was not tested
  8. 2020 High

    The broader OXTR circuit architecture was mapped by generating an Oxtr-ires-Cre knock-in prairie vole and identifying OXTR+ projections from multiple cortical, thalamic, and amygdala regions to nucleus accumbens, including a species-specific ACC→NAcc projection.

    Evidence CRISPR/Cas9 knock-in, retrograde Cre-dependent AAV tracing, and mRNA in situ hybridization in prairie voles

    PMID:33092784

    Open questions at the time
    • Functional significance of individual OXTR+ projections to NAcc not tested
    • Cross-species conservation of ACC→NAcc pathway not confirmed
  9. 2021 High

    A second OXTR+ brain circuit was functionally dissected: septal OXTR-expressing neurons project GABAergic fibers to HDB, and optogenetic activation of this projection inhibits HDB neurons and increases anxiety, defining an inhibitory mechanism for OXTR-mediated anxiety.

    Evidence Chemogenetics, optogenetics, tract tracing, and electrophysiology in OXTR-expressing septal neurons of mice

    PMID:34489531

    Open questions at the time
    • Whether oxytocin ligand or tonic OXTR activity drives anxiety in this circuit is not resolved
    • Interaction with the OXTR+ LS→CA1 social memory circuit not examined
  10. 2021 High

    How progesterone maintains uterine quiescence was answered by showing PGR-B suppresses Oxtr and Trpc3 while upregulating Plcl2, defining a PGR-B→Oxtr–Plcl2–Trpc3 contractile suppression axis.

    Evidence Transgenic mice overexpressing PGR-A or PGR-B in smooth muscle, uterine RNA-seq, ex vivo and in vivo contractility, CRISPRa for PLCL2/PLCL1

    PMID:33707208

    Open questions at the time
    • Whether PGR-B directly binds the Oxtr promoter or acts indirectly is unknown
    • Relevance to human preterm labor not validated
  11. 2022 High

    OXTR's role outside classical neuroendocrine contexts was extended to cancer by defining an OXTR→Gαq/CDC37→ERK5→CCL26 signaling axis in cancer-associated fibroblasts that drives invasion of CCR3+ oral squamous cell carcinoma cells.

    Evidence Co-immunoprecipitation, RNA-seq, ERK5 ablation, CCL26 neutralization, and invasion assays in OSCC patient tissue and cell models

    PMID:36045118

    Open questions at the time
    • Source of oxytocin ligand in the tumor microenvironment not identified
    • Whether this axis operates in other cancer types is unknown
  12. 2022 Medium

    A non-signaling pathological role for OXTR protein was identified: accumulated glycosaminoglycans in MPS I/II patient cells drive OXTR protein aggregation independent of gene expression changes, reversible by enzyme replacement.

    Evidence Immunofluorescence for OXTR aggregates in MPS patient-derived cells, enzyme replacement treatment

    PMID:35537249

    Open questions at the time
    • Whether OXTR aggregates impair receptor signaling is not tested
    • Mechanism of GAG-OXTR interaction (direct binding vs. indirect) not defined
  13. 2023 Medium

    OXTR engagement in neuroinflammation was defined by showing that intranasal OXT acts through hippocampal OXTR and an ERK–STAT3 pathway to reduce microglial overactivation and restore cognitive function in sepsis-associated encephalopathy.

    Evidence CLP mouse model, OXTR antagonist L-368,899, RNA-seq pathway analysis, microglial phagocytosis assay, and behavioral testing

    PMID:37648002

    Open questions at the time
    • ERK–STAT3 pathway activation shown by transcriptomics, not by direct biochemical assays of phosphorylation
    • Cell-type specificity of OXTR signaling in hippocampus (neurons vs. microglia) not resolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include: (1) whether TET1 acts directly at the Oxtr locus or through intermediate regulators, (2) the molecular mechanism by which OXTR+ LS→CA1 projections encode social memory, (3) the source of oxytocin ligand in the tumor microenvironment that activates OXTR on CAFs, and (4) whether distinct OXTR downstream signaling cascades (Gαq/ERK5 vs. nNOS/NO vs. ERK/STAT3) are determined by cell-type-specific coupling partners.
  • No structural basis for OXTR coupling selectivity to different Gα proteins
  • Relative contributions of OXTR signaling vs. OXTR-expressing circuit identity to behavioral phenotypes not disentangled
  • No reconstitution of any OXTR downstream pathway in a minimal system

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0060089 molecular transducer activity 5
Localization
GO:0005886 plasma membrane 3 GO:0005634 nucleus 1
Pathway
R-HSA-112316 Neuronal System 3 R-HSA-1474165 Reproduction 3 R-HSA-162582 Signal Transduction 3 R-HSA-4839726 Chromatin organization 3
Partners
CDC37ERK5GNAQNOS1PGRPLCL2TET1TRPC3

Evidence

Reading pass · 17 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2009 OTR and OXT transcripts are expressed in enteric neurons and intestinal epithelium, with OTR immunoreactivity co-localizing 100% with the neural marker Hu in postnatal day 3 myenteric plexus neurons; intrinsic primary afferent neurons express OTR, and OTR is present at enterocyte adherens junctions as shown by immunoelectron microscopy, suggesting a role for OT/OTR signaling in ENS development and visceral sensory modulation. RT-PCR, immunofluorescence co-localization, immunoelectron microscopy, subcellular fractionation The Journal of comparative neurology Medium 19003903
2012 Overexpression of oxytocin receptor (OTR) protein in myometrial smooth muscle cells (MSMCs) from adenomyosis patients correlates with increased uterine contractile amplitude; histone deacetylase inhibitor TSA and andrographolide dose-dependently inhibit OTR expression in MSMCs, implicating epigenetic regulation of OXTR in uterine contractility. Western blot quantification of OTR in cultured MSMCs, in vitro contractility assay, pharmacological inhibition (TSA, andrographolide) Fertility and sterility Medium 22999795
2014 Oxytocin down-regulates mesenteric afferent sensitivity via an OTR/nNOS/NO/KATP pathway: OTR co-localizes with nNOS in the longitudinal muscle myenteric plexus, and the inhibitory effect of oxytocin on bradykinin- or distention-evoked afferent discharge is blocked by the NOS inhibitors L-NAME and NPLA, and by KATP channel blocker glibenclamide. In vitro mesenteric afferent discharge recording, immunofluorescence co-localization, pharmacological dissection with NOS inhibitors and KATP blockers Neurogastroenterology and motility High 25346204
2014 Positive selection footprints are detected at OXTR amino acid sites across primates, with several OXTR changes promoting gain or loss of putative phosphorylation sites that may affect receptor internalization and desensitization; intramolecular and intermolecular coevolutionary processes between OXT and OXTR were detected. Phylogenetic analysis of OXT and OXTR sequences from 29 primate species, molecular dynamic simulations, coevolutionary analysis Proceedings of the National Academy of Sciences of the United States of America Medium 25535371
2015 Myometrial contractile activity during labor upregulates OXTR expression approximately 3.2–6.9-fold in placental trophoblast cells obtained from the maternal surface, compared to cesarean section without uterine contractions, suggesting a mechanosensitive positive-feedback regulation of OXTR in labor. Immunohistochemistry with morphometry, primary trophoblast cell culture, comparison of vaginal delivery vs. cesarean section placentae BMC pregnancy and childbirth Medium 26377392
2018 TET1 deficiency causes hypermethylation of CpG islands in Oxtr during early development, reducing select Oxtr mRNA isoforms in the brain of Tet1Δe4-/- mice; this is associated with impaired maternal care, social behavior, and synaptic responses to oxytocin stimulation, establishing TET1 as an epigenetic writer that maintains Oxtr expression by preventing DNA hypermethylation. Tet1 mutant mouse generation (CRISPR/Cas9 deletion of exon 4), RT-PCR for mRNA isoforms, bisulfite sequencing of CpG islands, behavioral assays, synaptic electrophysiology JCI insight High 30518695
2021 Progesterone receptor isoform B (PGR-B) suppresses uterine contractility by reducing Oxtr and Trpc3 expression while increasing Plcl2, establishing an Oxtr-Plcl2-Trpc3 pathway downstream of PGR-B; both PLCL2 and PLCL1 attenuate uterine muscle cell contraction in a CRISPRa-based assay, confirming this as a functional suppressive pathway. Transgenic mouse models (PGR-A or PGR-B overexpression in smooth muscle), uterine RNA sequencing, ex vivo and in vivo contractility assays, CRISPRa functional assay for PLCL2/PLCL1 Proceedings of the National Academy of Sciences of the United States of America High 33707208
2021 Chemogenetic activation of septal OXTr-expressing neurons induces anxiety-like but not depressive-like behavior; these neurons project GABAergic fibers to the horizontal diagonal band of Broca (HDB), and optogenetic stimulation of septal OXTr projections to HDB inactivates HDB neurons, revealing an inhibitory circuit mechanism by which OXTR-expressing septal neurons increase anxiety. Chemogenetics (DREADDs), optogenetics, anterograde tract tracing, electrophysiology, behavioral assays in mice Molecular psychiatry High 34489531
2020 Using Oxtr-ires-Cre knock-in prairie voles, OXTR-expressing neurons projecting to the nucleus accumbens (NAcc) were identified in multiple brain regions including anterior olfactory nucleus, PFC, ACC, insular cortex, paraventricular thalamus, basolateral amygdala, and cortical amygdaloid areas, establishing a detailed OXTR neural circuit map in the prairie vole, including a species-specific ACC→NAcc OXTR projection. CRISPR/Cas9 Oxtr-ires-Cre knock-in generation, retrograde Cre-dependent AAV tracing, fluorescence visualization, mRNA co-localization by in situ hybridization Neuroscience High 33092784
2020 Selective chemogenetic activation of OXTR-expressing neurons in the lateral septum (LS) rescues impaired social memory in both environmentally- (valproic acid) and genetically- (Nl3R451C knock-in) induced ASD mouse models; LS OXTR+ neurons are activated by social stimuli and project to the CA1 region of the hippocampus. Chemogenetics (hM3Dq DREADDs) in OXTR+ LS neurons, three-chamber social test, single-field social memory test, anterograde projection tracing in ASD mouse models Scientific reports High 33335150
2022 In oral squamous cell carcinoma, OXTRHigh cancer-associated fibroblasts (CAFs) activate nuclear ERK5 transcriptional signaling via Gαq and CDC37, maintaining high levels of OXTR and CCL26; CCL26 drives invasion of CCR3+ tumor cells, and ERK5 ablation reprograms the pro-invasive phenotype, establishing an OXTR→Gαq/CDC37→ERK5→CCL26 signaling axis in CAFs. Co-immunoprecipitation, RNA-seq, ERK5 ablation, CCL26 neutralization, invasion assays, OSCC patient tissue analysis Nature communications High 36045118
2023 In a sepsis-associated encephalopathy mouse model, hippocampal OXTR increases after CLP surgery; OXTR antagonist L-368,899 blocks intranasal OXT-mediated neuroprotection, and RNA sequencing identifies the OXTR-ERK-STAT3 signaling pathway as the mechanism by which OXT reduces microglial overactivation, restores synaptic function, and improves cognitive outcomes. CLP mouse model, intranasal OXT administration, OXTR antagonist injection (intraperitoneal and hippocampal CA1), RNA sequencing, microglial phagocytosis assay, cytokine measurement, behavioral assays Brain, behavior, and immunity Medium 37648002
2022 OXTR protein forms aggregates in MPS I and MPS II patient-derived cells due to interactions with accumulated glycosaminoglycans (GAGs); these aggregates disappear upon treatment with the deficient enzymes that degrade GAGs, indicating that GAG accumulation drives OXTR aggregate formation independent of changes in OXTR gene expression or protein levels. Transcriptomic analysis, immunofluorescence for OXTR aggregates in MPS patient cells, enzyme replacement treatment, correlation analysis of expression vs. aggregate formation European journal of cell biology Medium 35537249
2019 Maternal high fat diet-induced obesity increases Oxtr mRNA ~2-fold in male but not female offspring hippocampus at gestational day 17.5, associated with increased binding of the active histone mark H3K9Ac at the Oxtr transcriptional start site, demonstrating sex-specific epigenetic upregulation of Oxtr by maternal obesity. RT-PCR for Oxtr mRNA, chromatin immunoprecipitation (ChIP) for H3K9Ac at Oxtr TSS in offspring hippocampus, sex-stratified analysis International journal of molecular sciences Medium 30650536
2019 Perinatal bisphenol A (BPA) exposure eliminates sex differences in OTR expression in three hypothalamic regions of juvenile rats, with male OTR expression being more susceptible, as measured by receptor binding; this demonstrates that an endocrine-disrupting chemical can alter OTR expression in a sex- and brain-region-specific manner. Gavage BPA exposure spanning gestation and lactation in rats, OTR receptor binding assay across brain regions in juvenile offspring Neurotoxicology Medium 31251963
2010 Allelic expression imbalance (AEI) assays in lymphoblast cell lines and amygdala tissue identify cis-acting OXTR variants: rs237897 and rs237895 are associated with differential allelic abundance in lymphoblasts, and rs237895 also shows AEI in amygdala, while rs13316193 weakly correlates with total amygdala OXTR gene expression. Allelic expression imbalance (AEI) assay in lymphoblast cell lines and human amygdala tissue, correlation of genotype with RNA levels Neuroscience letters Medium 20303388
2019 In a bioinformatic analysis, the rs1042778 G allele of OXTR creates a binding site for the transcription factor MAZ; when the T allele is present, MAZ cannot bind, suggesting lower transcriptional activity of the OXTR gene as a functional consequence of this SNP. Bioinformatic transcription factor binding site prediction for rs1042778 alleles Journal of molecular neuroscience : MN Low 29858823

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2005 Positive association of the oxytocin receptor gene (OXTR) with autism in the Chinese Han population. Biological psychiatry 377 15992526
2008 Oxytocin receptor (OXTR) and serotonin transporter (5-HTT) genes associated with observed parenting. Social cognitive and affective neuroscience 337 19015103
2012 Sensitive parenting is associated with plasma oxytocin and polymorphisms in the OXTR and CD38 genes. Biological psychiatry 274 22336563
2014 The oxytocin receptor gene (OXTR) is associated with autism spectrum disorder: a meta-analysis. Molecular psychiatry 254 25092245
2010 Culture, distress, and oxytocin receptor polymorphism (OXTR) interact to influence emotional support seeking. Proceedings of the National Academy of Sciences of the United States of America 197 20724662
2012 Dynamic changes in DNA methylation of stress-associated genes (OXTR, BDNF ) after acute psychosocial stress. Translational psychiatry 186 22892716
2011 Oxytocin receptor gene (OXTR) is related to psychological resources. Proceedings of the National Academy of Sciences of the United States of America 182 21896752
2014 Plasma oxytocin concentrations and OXTR polymorphisms predict social impairments in children with and without autism spectrum disorder. Proceedings of the National Academy of Sciences of the United States of America 178 25092315
2009 The oxytocin receptor (OXTR) contributes to prosocial fund allocations in the dictator game and the social value orientations task. PloS one 164 19461999
2010 Association of the oxytocin receptor (OXTR) gene polymorphisms with autism spectrum disorder (ASD) in the Japanese population. Journal of human genetics 146 20094064
2014 Environmental risk, Oxytocin Receptor Gene (OXTR) methylation and youth callous-unemotional traits: a 13-year longitudinal study. Molecular psychiatry 143 25199917
2013 Common polymorphism in the oxytocin receptor gene (OXTR) is associated with human social recognition skills. Proceedings of the National Academy of Sciences of the United States of America 141 24367110
2012 The association between oxytocin receptor gene polymorphism (OXTR) and trait empathy. Journal of affective disorders 141 22357335
2011 Association of oxytocin receptor (OXTR) gene variants with multiple phenotype domains of autism spectrum disorder. Journal of neurodevelopmental disorders 123 21484202
2010 Evidence for the involvement of genetic variation in the oxytocin receptor gene (OXTR) in the etiology of autistic disorders on high-functioning level. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 120 19777562
2009 Expression and developmental regulation of oxytocin (OT) and oxytocin receptors (OTR) in the enteric nervous system (ENS) and intestinal epithelium. The Journal of comparative neurology 110 19003903
2015 Association of Oxytocin Receptor Gene (OXTR) rs53576 Polymorphism with Sociality: A Meta-Analysis. PloS one 103 26121678
2018 The role of oxytocin receptor gene (OXTR) DNA methylation (DNAm) in human social and emotional functioning: a systematic narrative review. BMC psychiatry 98 29843655
2012 Dysmenorrhea and its severity are associated with increased uterine contractility and overexpression of oxytocin receptor (OTR) in women with symptomatic adenomyosis. Fertility and sterility 91 22999795
2012 Does the oxytocin receptor (OXTR) polymorphism (rs2254298) confer 'vulnerability' for psychopathology or 'differential susceptibility'? Insights from evolution. BMC medicine 89 22510359
2011 Oxytocin Receptor (OXTR) Polymorphisms and Attachment in Human Infants. Frontiers in psychology 75 21904531
2010 Oxytocin receptor (OXTR) does not play a major role in the aetiology of autism: genetic and molecular studies. Neuroscience letters 74 20303388
2015 A common oxytocin receptor gene (OXTR) polymorphism modulates intranasal oxytocin effects on the neural response to social cooperation in humans. Genes, brain, and behavior 73 26178189
2016 Prenatal stress exposure, oxytocin receptor gene (OXTR) methylation, and child autistic traits: The moderating role of OXTR rs53576 genotype. Autism research : official journal of the International Society for Autism Research 72 27520745
2008 Molecular genetic studies of the arginine vasopressin 1a receptor (AVPR1a) and the oxytocin receptor (OXTR) in human behaviour: from autism to altruism with some notes in between. Progress in brain research 70 18655900
2017 Revisiting the impact of OXTR rs53576 on empathy: A population-based study and a meta-analysis. Psychoneuroendocrinology 67 28343138
2015 Methylation of the oxytocin receptor gene in clinically depressed patients compared to controls: The role of OXTR rs53576 genotype. Journal of psychiatric research 66 25890851
2012 The influence of oxytocin administration on responses to infant faces and potential moderation by OXTR genotype. Psychopharmacology 66 22763666
2013 Cumulative risk on the oxytocin receptor gene (OXTR) underpins empathic communication difficulties at the first stages of romantic love. Social cognitive and affective neuroscience 61 23974948
2010 Evidence that genetic variation in the oxytocin receptor (OXTR) gene influences social cognition in ADHD. Progress in neuro-psychopharmacology & biological psychiatry 60 20347913
2018 Associations between oxytocin receptor gene (OXTR) methylation, plasma oxytocin, and attachment across adulthood. International journal of psychophysiology : official journal of the International Organization of Psychophysiology 56 29410310
2014 Genetic imaging of the association of oxytocin receptor gene (OXTR) polymorphisms with positive maternal parenting. Frontiers in behavioral neuroscience 54 24550797
2017 Oxytocin receptors (OXTR) and early parental care: An interaction that modulates psychiatric disorders. Research in developmental disabilities 53 29033100
2010 The association between oxytocin receptor gene (OXTR) polymorphisms and affective temperaments, as measured by TEMPS-A. Journal of affective disorders 52 20488544
2016 Maternal adversities during pregnancy and cord blood oxytocin receptor (OXTR) DNA methylation. Social cognitive and affective neuroscience 50 27107296
2020 Resolving the formidable barrier of oxygen transferring rate (OTR) in ultrahigh-titer bioconversion/biocatalysis by a sealed-oxygen supply biotechnology (SOS). Biotechnology for biofuels 49 31911817
2023 Oxytocin alleviates cognitive and memory impairments by decreasing hippocampal microglial activation and synaptic defects via OXTR/ERK/STAT3 pathway in a mouse model of sepsis-associated encephalopathy. Brain, behavior, and immunity 48 37648002
2015 Oxytocin Receptor (OXTR) Single Nucleotide Polymorphisms Indirectly Predict Prosocial Behavior Through Perspective Taking and Empathic Concern. Journal of personality 47 25403479
2014 Genetic variation in the oxytocin receptor (OXTR) gene is associated with Asperger Syndrome. Molecular autism 47 25264479
2012 Differential susceptibility in spillover between interparental conflict and maternal parenting practices: evidence for OXTR and 5-HTT genes. Journal of family psychology : JFP : journal of the Division of Family Psychology of the American Psychological Association (Division 43) 46 22563705
2018 Epigenetic variability in the human oxytocin receptor (OXTR) gene: A possible pathway from early life experiences to psychopathologies. Neuroscience and biobehavioral reviews 45 30496762
2023 Roles of the Oxytocin Receptor (OXTR) in Human Diseases. International journal of molecular sciences 43 36835321
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 43 30650536
2014 Evolutionary pattern in the OXT-OXTR system in primates: coevolution and positive selection footprints. Proceedings of the National Academy of Sciences of the United States of America 42 25535371
2016 ASD and Genetic Associations with Receptors for Oxytocin and Vasopressin-AVPR1A, AVPR1B, and OXTR. Frontiers in neuroscience 40 27920663
2014 Association between the oxytocin receptor (OXTR) gene and mesolimbic responses to rewards. Molecular autism 40 24485285
2018 Intranasal oxytocin and OXTR genotype effects on resting state functional connectivity: A systematic review. Neuroscience and biobehavioral reviews 38 30243577
2022 OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling. Nature communications 36 36045118
2017 A functional polymorphism of the OXTR gene is associated with autistic traits in Caucasian and Asian populations. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 35 29027364
2015 Chimpanzee sociability is associated with vasopressin (Avpr1a) but not oxytocin receptor gene (OXTR) variation. Hormones and behavior 35 26299644
2020 Imaging-genetics of sex differences in ASD: distinct effects of OXTR variants on brain connectivity. Translational psychiatry 34 32127526
2013 Environmental stress, oxytocin receptor gene (OXTR) polymorphism, and mental health following collective stress. Hormones and behavior 33 23470776
2013 Variant in OXTR gene and functional connectivity of the hypothalamus in normal subjects. NeuroImage 33 23684879
2019 Perinatal bisphenol A (BPA) exposure alters brain oxytocin receptor (OTR) expression in a sex- and region- specific manner: A CLARITY-BPA consortium follow-up study. Neurotoxicology 32 31251963
2014 Association between the oxytocin receptor (OXTR) gene and children's social cognition at 18 months. Genes, brain, and behavior 31 24916666
2013 Are genetic variations in OXTR, AVPR1A, and CD38 genes important to social integration? Results from two large U.S. cohorts. Psychoneuroendocrinology 31 24209975
2020 Investigation of Oxtr-expressing Neurons Projecting to Nucleus Accumbens using Oxtr-ires-Cre Knock-in prairie Voles (Microtus ochrogaster). Neuroscience 30 33092784
2020 Targeting oxytocin receptor (Oxtr)-expressing neurons in the lateral septum to restore social novelty in autism spectrum disorder mouse models. Scientific reports 30 33335150
2021 Progesterone receptor isoform B regulates the Oxtr-Plcl2-Trpc3 pathway to suppress uterine contractility. Proceedings of the National Academy of Sciences of the United States of America 28 33707208
2022 Oxytocin receptor gene (OXTR) polymorphisms and social, emotional and behavioral functioning in children and adolescents: A systematic narrative review. Neuroscience and biobehavioral reviews 27 35149102
2021 An epigenetic rheostat of experience: DNA methylation of OXTR as a mechanism of early life allostasis. Comprehensive psychoneuroendocrinology 26 35757665
2013 The association between the oxytocin receptor gene (OXTR) and hypnotizability. Psychoneuroendocrinology 26 23562248
2019 Interaction effect of oxytocin receptor (OXTR) rs53576 genotype and maternal postpartum depression on child behavioural problems. Scientific reports 25 31118457
2017 Social Behavior of Pet Dogs Is Associated with Peripheral OXTR Methylation. Frontiers in psychology 25 28443051
2014 Behavioral responses to pups in males with different reproductive experiences are associated with changes in central OT, TH and OTR, D1R, D2R mRNA expression in mandarin voles. Hormones and behavior 25 25496756
2021 Activation of septal OXTr neurons induces anxiety- but not depressive-like behaviors. Molecular psychiatry 24 34489531
2019 Methylation of the OXTR gene in women with anorexia nervosa: Relationship to social behavior. European eating disorders review : the journal of the Eating Disorders Association 24 31823473
2018 The OXTR Single-Nucleotide Polymorphism rs53576 Moderates the Impact of Childhood Maltreatment on Empathy for Social Pain in Female Participants: Evidence for Differential Susceptibility. Frontiers in psychiatry 24 30135663
2018 Epigenetic dysregulation of Oxtr in Tet1-deficient mice has implications for neuropsychiatric disorders. JCI insight 24 30518695
2016 Variation in the oxytocin receptor gene (OXTR) is associated with differences in moral judgment. Social cognitive and affective neuroscience 24 27497314
2014 Personality, behavior and environmental features associated with OXTR genetic variants in British mothers. PloS one 24 24621820
2010 Dermatologic management, sun avoidance and vitamin D status in organ transplant recipients (OTR). Journal of photochemistry and photobiology. B, Biology 24 20434355
2021 Hypermethylation of the oxytocin receptor gene (OXTR) in obsessive-compulsive disorder: further evidence for a biomarker of disease and treatment response. Epigenetics 23 34269138
2016 Relationship of a common OXTR gene variant to brain structure and default mode network function in healthy humans. NeuroImage 23 28017919
2016 Congenital prosopagnosia is associated with a genetic variation in the oxytocin receptor (OXTR) gene: An exploratory study. Neuroscience 22 27693815
2021 Oxtr/TRPV1 expression and acclimation of skeletal muscle to cold-stress in male mice. The Journal of endocrinology 21 33705350
2015 Myometrial contractility influences oxytocin receptor (OXTR) expression in term trophoblast cells obtained from the maternal surface of the human placenta. BMC pregnancy and childbirth 20 26377392
2012 Sexually dimorphic effects of oxytocin receptor gene (OXTR ) variants on Harm Avoidance. Biology of sex differences 20 22846218
2021 The influence of rs53576 polymorphism in the oxytocin receptor (OXTR) gene on empathy in healthy adults by subtype and ethnicity: a systematic review and meta-analysis. Reviews in the neurosciences 19 33892530
2012 Influence of COX-2 and OXTR polymorphisms on treatment outcome in treatment resistant depression. Neuroscience letters 19 22487732
2016 Lessons from the canine Oxtr gene: populations, variants and functional aspects. Genes, brain, and behavior 18 27860243
2014 Oxytocin down-regulates mesenteric afferent sensitivity via the enteric OTR/nNOS/NO/KATP pathway in rat. Neurogastroenterology and motility 18 25346204
2020 Interactions of OXTR rs53576 and emotional trauma on hippocampal volumes and perceived social support in adolescent girls. Psychoneuroendocrinology 17 32199286
2018 DNA methylation of OXTR is associated with parasympathetic nervous system activity and amygdala morphology. Social cognitive and affective neuroscience 17 30257007
2012 The expression of ERα, OTR, cPLA(2), COX-2, and PPARγ in the cervix of the ewe during the estrous cycle. Theriogenology 17 23117133
2017 Sequence variants in ESR1 and OXTR are associated with Mayer-Rokitansky-Küster-Hauser syndrome. Acta obstetricia et gynecologica Scandinavica 15 28815558
2013 Navigating the complex path between the oxytocin receptor gene (OXTR) and cooperation: an endophenotype approach. Frontiers in human neuroscience 15 24348360
2020 Oxytocin Prevents the Development of 3-NP-Induced Anxiety and Depression in Male and Female Rats: Possible Interaction of OXTR and mGluR2. Cellular and molecular neurobiology 14 33201416
2018 Evidence for Association Between OXTR Gene and ASD Clinical Phenotypes. Journal of molecular neuroscience : MN 14 29858823
2016 The Oxytocin Receptor Gene ( OXTR) and Face Recognition. Psychological science 14 27837182
2005 PCR detection of oxytetracycline resistance genes otr(A) and otr(B) in tetracycline-resistant streptomycete isolates from diverse habitats. Current microbiology 14 16132462
2020 Burnout in university faculty: An interaction between subjective sleep quality and the OXTR rs2268498 polymorphism. Journal of affective disorders 13 32739712
2020 Oxytocin Receptor Gene (OXTR) and Childhood Adversity Influence Trust. Psychoneuroendocrinology 13 32866773
2019 Associations between oxytocin receptor gene (OXTR) polymorphisms, childhood trauma, and parenting behavior. Developmental psychology 13 31282733
2017 How Oxytocin Receptor (OXTR) Single Nucleotide Polymorphisms Act on Prosociality: The Mediation Role of Moral Evaluation. Frontiers in psychology 13 28377734
2015 Novel rare variations of the oxytocin receptor (OXTR) gene in autism spectrum disorder individuals. Human genome variation 13 27081536
2022 Changes in expression of signal transduction-related genes, and formation of aggregates of GPER1 and OXTR receptors in mucopolysaccharidosis cells. European journal of cell biology 12 35537249
2020 The Association of Oxytocin Receptor Gene (OXTR) Polymorphisms with Antisocial Behavior: A Meta-analysis. Behavior genetics 12 32060678
2016 Oxytocin Receptor (OXTR) Methylation and Cognition in Psychotic Disorders. Molecular neuropsychiatry 12 27867940
2017 The OXTR gene, implicit learning and social processing: Does empathy evolve from perceptual skills for details? Behavioural brain research 11 28442360