Evidence map›Paper›PMID 31415088›Full record

ArticleEndocrinology2019

Prenatal Testosterone Exposure Alters GABAergic Synaptic Inputs to GnRH and KNDy Neurons in a Sheep Model of Polycystic Ovarian Syndrome.

Danielle T Porter, Aleisha M Moore, Jade A Cobern, Vasantha Padmanabhan, Robert L Goodman, Lique M Coolen, Michael N Lehman

Open access · bronzeAbstract read
In one paragraph

Article in Endocrinology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.

0numbers the graph read from it
0cells of the map it votes in
29citing papers in PubMed
5.9field-weighted citation impact, top 4% 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

29 citing papers in PubMed, 56 citations in OpenAlex.

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4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

7 authors at 4 institutions in 1 country.

Danielle T PorterGraduate Program in Neuroscience, Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi.
Aleisha M MooreBrain Health Research Institute, Kent State University, Kent, Ohio.
Jade A CobernGraduate Program in Neuroscience, Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi.
Vasantha PadmanabhanDepartment of Pediatrics, University of Michigan, Ann Arbor, Michigan.
Robert L GoodmanDepartment of Physiology and Pharmacology, West Virginia University, Morgantown, West Virginia.
Lique M CoolenGraduate Program in Neuroscience, Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi.
Michael N LehmanGraduate Program in Neuroscience, Department of Neurobiology and Anatomical Sciences, University of Mississippi Medical Center, Jackson, Mississippi.
Kent State University · USUniversity of Mississippi Medical Center · USUniversity of Michigan · USWest Virginia University · US

Funding

STEROIDAL AND METABOLIC MEDIATION OF NEUROENDOCRINE CIRCUITRYP01HD044232 · NICHD · UNIVERSITY OF MICHIGAN AT ANN ARBOR · PI PADMANABHAN, VASANTHA · 2004 to 2015
$12.9M
NICHD NIH HHS P01 HD044232
6 · The paper itself

Abstract

Prenatal testosterone (T)-treated female sheep display reproductive deficits similar to women with polycystic ovarian syndrome (PCOS), including an increase in LH pulse frequency due to actions of the central GnRH pulse generator. In this study, we used multiple-label immunocytochemistry to investigate the possibility of changes in the γ-aminobutyric acid (GABA) neurotransmitter system at two key components of the GnRH pulse generator in prenatal T-treated sheep: kisspeptin/neurokinin B/dynorphin (KNDy) neurons of the arcuate nucleus, and GnRH neurons in the preoptic area (POA) and mediobasal hypothalamus (MBH). We observed a significant decrease and increase, respectively, in the number of GABAergic synapses onto POA and MBH GnRH neurons in prenatal T-treated ewes; additionally, there was a significant increase in the number of GABAergic inputs onto KNDy neurons. To determine the actions of GABA on GnRH and KNDy neurons, we examined colocalization with the chloride transporters NKCC1 and KCC2, which indicate stimulatory or inhibitory activation of neurons by GABA, respectively. Most GnRH neurons in both POA and MBH colocalized NKCC1 cotransporter whereas none contained the KCC2 cotransporter. Most KNDy neurons colocalized either NKCC1 or KCC2, and 28% of the KNDy population contained NKCC1 alone. Therefore, we suggest that, as in the mouse, GABA in the sheep is stimulatory to GnRH neurons, as well as to a subset of KNDy neurons. Increased numbers of stimulatory GABAergic inputs to both MBH GnRH and KNDy neurons in prenatal T-treated animals may contribute to alterations in steroid feedback control and increased GnRH/LH pulse frequency seen in this animal model of PCOS.

Indexed as

AnimalsArcuate Nucleus of HypothalamusDisease Models, AnimalDynorphinsFemaleGABAergic NeuronsGonadotropin-Releasing HormoneK Cl- CotransportersKisspeptinsNeurokinin BPolycystic Ovary SyndromePregnancyPrenatal Exposure Delayed EffectsPreoptic AreaSheepSolute Carrier Family 12, Member 2DynorphinsGonadotropin-Releasing HormoneK Cl- CotransportersKisspeptinsNeurokinin BSolute Carrier Family 12, Member 2SymportersTestosterone

Identifiers

PMID31415088
PMCPMC6779074
OpenAlexW2967943123

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.