Evidence map›Paper›PMID 35128447›Full record

ArticleReproduction & fertility2021

Nitric oxide positively affects endometrial receptivity via FAAH and NAPE-PLD

Sarah E Melford, Anthony H Taylor, Justin C Konje

Open access · diamondAbstract read
In one paragraph

Article in Reproduction & fertility, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.

0numbers the graph read from it
0cells of the map it votes in
4citing papers in PubMed, 1 pooled it
0.5field-weighted citation impact, top 35% 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

4 citing papers in PubMed, 1 synthesis or guideline pooled it, 4 citations in OpenAlex.

  1. Unlocking Implantation: The Role of Nitric Oxide, NOInternational journal of molecular sciences · 2025
    Pooled it
  2. Review
  3. Article
  4. Review
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

3 authors at 1 institution in 1 country.

Sarah E MelfordEndocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
Anthony H TaylorEndocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
Justin C KonjeEndocannabinoid Research Group, Reproductive Sciences Section, Department of Cancer Studies and Molecular Medicine, University of Leicester, Leicester, UK.
University of Leicester · GB

Funding

Department of Health PB-PG-0909-19305
6 · The paper itself

Abstract

objectiveTo determine if models of human 'receptive' and 'non-receptive endometrium' differ in their responses to nitric oxide (NO) supplementation by measuring the levels of the enzymes of the endocannabinoid system (ECS) (fatty acid amide hydrolase (FAAH) and N-acylphosphatidylethanolamine-specific phospholipase D (NAPE-PLD)), which control the 'anandamide tone' essential for successful pregnancy.

designA study of FAAH and NAPE-PLD expression (using human endometrium) through the menstrual cycle and an

resultsImmunoreactivity measured by optimised H-score for both FAAH and NAPE-PLD was reduced in secretory (receptive) endometrium compared to proliferative (non-receptive) endometrium (

conclusionThese data suggest that NO most likely affects the expression of ECS enzymes in the implantation site of a receptive endometrium; a phenomenon not seen in a non-receptive endometrium. These effects are most marked with FAAH expression, suggesting that FAAH may play the more critical role in ensuring the correct 'anandamide tone' for successful embryo implantation than NAPE-PLD. LAY SUMMARY: Embryo implantation into the wall of the uterus is only successful when the inner wall of the uterus (the endometrium) is 'receptive', because if it is 'non-receptive', implantation will fail. Previous work showed that enzymes of the 'endocannabinoid system' are critical for implantation by maintaining the correct level of a fat called anandamide. This is by balancing its synthesis (by N-acylphosphatidylethanolamine specific phospholipase D, NAPE-PLD) and degradation (by fatty acid amide hydrolase, FAAH). Using immortalised cell lines as models of 'receptive' and 'non-receptive' human endometrium, we demonstrate a key stimulator of implantation, nitric oxide, has a positive effect on implantation by both increasing the mRNA levels of the degrading enzyme (FAAH) and decreasing the expression of the synthesising enzyme (NAPE-PLD). These effects are most marked with the degrading enzyme, suggesting that FAAH plays a more critical role than NAPE-PLD in ensuring the correct 'anandamide tone' for successful embryo implantation.

Indexed as

EndocannabinoidsPhospholipase DAmidohydrolasesEndometriumFatty Acid Amide HydrolasesFemaleHumansNitric OxidePhosphatidylethanolaminesPregnancyRNA, MessengerAmidohydrolasesEndocannabinoidsFatty Acid Amide HydrolasesN-acylphosphatidylethanolamineNitric OxidePhosphatidylethanolaminesPhospholipase DRNA, Messengerendocannabinoidendometrial receptivityfatty acid amide hydrolaseN-acylphosphatidylethanolaminenitric oxide

Identifiers

PMID35128447
PMCPMC8812446
OpenAlexW3147068865

What OpenQuestion holds

Textmetadata
LicenceCC BY
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.