Evidence map›Paper›PMID 27384303›Full record

ArticleEndocrinology2016

The Methylcytosine Dioxygenase Ten-Eleven Translocase-2 (tet2) Enables Elevated GnRH Gene Expression and Maintenance of Male Reproductive Function.

Joseph R Kurian, Somaja Louis, Kim L Keen, Andrew Wolfe, Ei Terasawa, Jon E Levine

Open access · hybridAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Endocrinology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.

0numbers the graph read from it
0cells of the map it votes in
21citing papers in PubMed
2.6field-weighted citation impact, top 10% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

21 citing papers in PubMed, 42 citations in OpenAlex.

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4 · The record

Corrections and comments

5 · Who and what money

Authors and funding

6 authors at 3 institutions in 1 country.

Joseph R KurianDepartment of Obstetrics and Gynecology (J.R.K., S.L.), Southern Illinois University School of Medicine, Springfield, Illinois 62794; St. John's Hospital Carol Jo Vecchie Women and Children's Center (J.R.K.), Springfield, Illinois 62769; Wisconsin National Primate Research Center (K.L.K., E.T., J.E.L.), Madison, Wisconsin 53705; Department of Pediatrics and Physiology (A.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Departments of Pediatrics (E.T.) and Neuroscience (J.E.L.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706.
Somaja LouisDepartment of Obstetrics and Gynecology (J.R.K., S.L.), Southern Illinois University School of Medicine, Springfield, Illinois 62794; St. John's Hospital Carol Jo Vecchie Women and Children's Center (J.R.K.), Springfield, Illinois 62769; Wisconsin National Primate Research Center (K.L.K., E.T., J.E.L.), Madison, Wisconsin 53705; Department of Pediatrics and Physiology (A.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Departments of Pediatrics (E.T.) and Neuroscience (J.E.L.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706.
Kim L KeenDepartment of Obstetrics and Gynecology (J.R.K., S.L.), Southern Illinois University School of Medicine, Springfield, Illinois 62794; St. John's Hospital Carol Jo Vecchie Women and Children's Center (J.R.K.), Springfield, Illinois 62769; Wisconsin National Primate Research Center (K.L.K., E.T., J.E.L.), Madison, Wisconsin 53705; Department of Pediatrics and Physiology (A.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Departments of Pediatrics (E.T.) and Neuroscience (J.E.L.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706.
Andrew WolfeDepartment of Obstetrics and Gynecology (J.R.K., S.L.), Southern Illinois University School of Medicine, Springfield, Illinois 62794; St. John's Hospital Carol Jo Vecchie Women and Children's Center (J.R.K.), Springfield, Illinois 62769; Wisconsin National Primate Research Center (K.L.K., E.T., J.E.L.), Madison, Wisconsin 53705; Department of Pediatrics and Physiology (A.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Departments of Pediatrics (E.T.) and Neuroscience (J.E.L.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706.
Ei TerasawaDepartment of Obstetrics and Gynecology (J.R.K., S.L.), Southern Illinois University School of Medicine, Springfield, Illinois 62794; St. John's Hospital Carol Jo Vecchie Women and Children's Center (J.R.K.), Springfield, Illinois 62769; Wisconsin National Primate Research Center (K.L.K., E.T., J.E.L.), Madison, Wisconsin 53705; Department of Pediatrics and Physiology (A.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Departments of Pediatrics (E.T.) and Neuroscience (J.E.L.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706.
Jon E LevineDepartment of Obstetrics and Gynecology (J.R.K., S.L.), Southern Illinois University School of Medicine, Springfield, Illinois 62794; St. John's Hospital Carol Jo Vecchie Women and Children's Center (J.R.K.), Springfield, Illinois 62769; Wisconsin National Primate Research Center (K.L.K., E.T., J.E.L.), Madison, Wisconsin 53705; Department of Pediatrics and Physiology (A.W.), The Johns Hopkins University School of Medicine, Baltimore, Maryland 21287; and Departments of Pediatrics (E.T.) and Neuroscience (J.E.L.), University of Wisconsin School of Medicine and Public Health, Madison, Wisconsin 53706.
Southern Illinois University School of Medicine · USUniversity of Wisconsin–Madison · USJohns Hopkins University · US

Funding

WNPRC Supplemental Request for Nonhuman Primate Enclosures to Equip HIV/AIDS-Related Research FacilitiesP51OD011106 · OD · UNIVERSITY OF WISCONSIN-MADISON · PI Dorota A. Grejner-Brzezinska · 2012 to 2026
$150.7M
HYPOTHALAMIC CONTROL OF PUBERTYR01HD011355 · NICHD · UNIVERSITY OF WISCONSIN-MADISON · PI TERASAWA-GRILLEY, EI · 1985 to 2011
$3.5M
Sex Steroids, Kisspeptin and Regulation of GnRHR01HD068777 · NICHD · RBHS-ROBERT WOOD JOHNSON MEDICAL SCHOOL · PI HOFFMAN, GLORIA E, LEVINE, JON E · 2012 to 2016
$2.4M
Growth Factor Regulation of the GnRH NeuronR01HD044608 · NICHD · UNIVERSITY OF CHICAGO · PI WOLFE, ANDREW M · 2003 to 2007
$1.2M
Influence of Endocrine Disruptors on Reproductive Neuroendocrine FunctionR00ES020878 · NIEHS · SOUTHERN ILLINOIS UNIVERSITY SCH OF MED · PI KURIAN, JOSEPH RAYMOND · 2014 to 2016
$747k
NICHD NIH HHS R01 HD011355NICHD NIH HHS R01 HD044608NICHD NIH HHS R01 HD068777NIEHS NIH HHS R00 ES020878NIH HHS P51 OD011106
6 · The paper itself

Abstract

Reproduction depends on the establishment and maintenance of elevated GnRH neurosecretion. The elevation of primate GnRH release is accompanied by epigenetic changes. Specifically, cytosine residues within the GnRH gene promoter are actively demethylated, whereas GnRH mRNA levels and peptide release rise. Whether active DNA demethylation has an impact on GnRH neuron development and consequently reproductive function remains unknown. In this study, we investigated whether ten-eleven translocation (tet) enzymes, which initiate the process of active DNA demethylation, influence neuronal function and reproduction. We found that tet2 expression increases with age in the developing mouse preoptic area-hypothalamus and is substantially higher in a mature (GT1-7) than an immature (GN11) GnRH cell line. GnRH mRNA levels and mean GnRH peptide release elevated after overexpression of tet2 in GN11 cells, whereas CRISPR/cas9-mediated knockdown of tet2 in GT1-7 cells led to a significant decline in GnRH expression. Manipulations of tet2 expression altered tet2 genome binding and histone 3 lysine 4 trimethylation abundance at the GnRH promoter. Mice with selective disruption of tet2 in GnRH neurons (GnRH-specific tet2 knockout mice) exhibited no sign of altered pubertal timing in either sex, although plasma LH levels were significantly lower, and fecundity was altered specifically in adult male GnRH-specific tet2 knockout animals, indicating that tet2 may participate in the maintenance GnRH neuronal function. Exposure to bisphenol A, an environmental contaminant that alters GnRH neuron activity, caused a shift in tet2 subcellular localization and a decrease in histone 3 lysine 4 trimethylation abundance at the GnRH promoter. Finally, evaluation of tet2 protein interactions in GT1-7 cells suggests that the influence of tet2 on neuronal function are not limited to nuclear mechanisms but could depend on mitochondrial function, and RNA metabolism. Together, these studies implicate tet2 in the maintenance of GnRH neuronal function and neuroendocrine control of male reproduction.

Indexed as

ReproductionAnimalsBenzhydryl CompoundsBisphenol A CompoundsCell LineDioxygenasesDNA-Binding ProteinsFemaleGene Expression Regulation, DevelopmentalGonadotropin-Releasing HormoneHistone CodeHumansMaleMiceNeuronsPhenolsBenzhydryl Compoundsbisphenol ABisphenol A CompoundsDioxygenasesDNA-Binding ProteinsGonadotropin-Releasing HormonePhenolsProto-Oncogene ProteinsTet2 protein, mouse

Identifiers

PMID27384303
PMCPMC5007894
OpenAlexW2463284938

What OpenQuestion holds

Textmetadata
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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.