Evidence map›Paper›PMID 25813289›Full record

ArticleFertility and sterility2015

Sildenafil stimulates human trophoblast invasion through nitric oxide and guanosine 3',5'-cyclic monophosphate signaling.

Jay M Bolnick, Brian A Kilburn, Alan D Bolnick, Michael P Diamond, Manvinder Singh, Michael Hertz, Jing Dai, D Randall Armant

Open access · bronzeAbstract read
In one paragraph

Article in Fertility and sterility, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.

0numbers the graph read from it
0cells of the map it votes in
12citing papers in PubMed
2.6field-weighted citation impact, top 11% 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

12 citing papers in PubMed, 21 citations in OpenAlex.

  1. Article
  2. Extract ofFoods (Basel, Switzerland) · 2023
    Article
  3. Article
  4. Article
  5. Abnormal cGMP-dependent protein kinase I-mediated decidualization in preeclampsia.Hypertension research : official journal of the Japanese Society of Hypertension · 2021
    Article
  6. Article
  7. Oxidative Stress in Preeclampsia and Placental Diseases.International journal of molecular sciences · 2018
    Review
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
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

8 authors at 3 institutions in 1 country.

Jay M BolnickDepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
Brian A KilburnDepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
Alan D BolnickDepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
Michael P DiamondDepartment of Obstetrics and Gynecology, Georgia Regents University, Augusta, Georgia.
Manvinder SinghDepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
Michael HertzDepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
Jing DaiDepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan.
D Randall ArmantDepartment of Obstetrics and Gynecology, Wayne State University School of Medicine, Detroit, Michigan; Department of Anatomy and Cell Biology, Wayne State University School of Medicine, Detroit, Michigan; Program in Reproductive and Adult Endocrinology, The Eunice Kennedy Shriver National Institute of Child Health and Human Development, National Institutes of Health, Bethesda, Maryland. Electronic address: D.Armant@Wayne.edu.
Wayne State University · USAugusta University · USNational Institutes of Health · US

Funding

Genetic Analysis of Human First Trimester Trophoblast in Ongoing PregnanciesR21HD071408 · NICHD · WAYNE STATE UNIVERSITY · PI ARMANT, DAVID RANDALL, DIAMOND, MICHAEL PETER · 2012 to 2013
$406k
NICHD NIH HHS HD071408NICHD NIH HHS R21 HD071408
6 · The paper itself

Abstract

objectiveTo determine the effect of sildenafil, a phosphodiesterase type 5 inhibitor, on trophoblast invasiveness.

designLaboratory investigation.

settingAcademic medical center. PATIENT(S): Placental tissues discarded after first-trimester terminations were obtained from patients with informed consent. INTERVENTION(S): A cell line, HTR-8/SVneo, established from first-trimester cytotrophoblast, and villous explants, was treated with or without sildenafil, guanosine 3',5'-cyclic monophosphate (cGMP) analog, cGMP inhibitor, or L-NAME (N(G)-nitro-L-arginine methyl ester hydrochloride) and cultured on fibronectin or Matrigel. Integrins α6β4 and α1β1 were detected by immunocytochemistry. MAIN OUTCOME MEASURE(S): Trophoblast outgrowth from villous tips, cytotrophoblast cell invasion, and integrin immunostaining were assessed in cytotrophoblast and explant cultures. RESULT(S): Integrin expression in trophoblast cells ex vivo switched from α6 to α1, and invasiveness increased, when exposed to sildenafil or cGMP agonist. Either cGMP antagonist or L-NAME blocked integrin switching and invasion induced by sildenafil. Elevation of nitric oxide pharmacologically induced invasion, but not when cGMP antagonist was present. CONCLUSION(S): Sildenafil altered trophoblast phenotype through a process dependent on nitric oxide availability and cGMP accumulation. In addition to its vasoactivity, sildenafil directly stimulates trophoblast extravillous differentiation, which would be favorable for implantation and reduce risk for adverse pregnancy outcomes.

Indexed as

Cell LineCell MovementCyclic GMPDose-Response Relationship, DrugEmbryo ImplantationFemaleHumansNitric OxidePiperazinesPurinesSignal TransductionSildenafil CitrateSulfonamidesTrophoblastsCyclic GMPNitric OxidePiperazinesPurinesSildenafil CitrateSulfonamidesguanosine 3′,5′-cyclic monophosphateintegrinsnitric oxidephosphodiesterase-5 inhibitorTrophoblast invasion

Identifiers

PMID25813289
PMCPMC10411948
OpenAlexW2082941945

What OpenQuestion holds

Textmetadata
LicenceTDM
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.