Evidence map›Paper›PMID 33291075›Full record

ArticleAging2020

The endothelial nitric oxide synthase/cyclic guanosine monophosphate/protein kinase G pathway activates primordial follicles.

Peikun Zhao, Zidai Song, Yan Wang, Han Cai, Xiaoyan Du, Changlong Li, Jianyi Lv, Xin Liu, Meng Guo, Zhenwen Chen

Open access · greenAbstract read
In one paragraph

Article in Aging, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.

0numbers the graph read from it
0cells of the map it votes in
6citing papers in PubMed
0.5field-weighted citation impact, top 27% 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

6 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Review
  5. Metabolic Control of Germline Formation and Differentiation in Mammals.Sexual development : genetics, molecular biology, evolution, endocrinology, embryology, and pathology of sex determination and differentiation · 2022
    Review
  6. 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

10 authors at 2 institutions in 1 country.

Peikun ZhaoBeijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China.
Zidai SongBeijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China.
Yan WangBeijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China.
Han CaiFujian Provincial Key Laboratory of Reproductive Health Research, Medical College of Xiamen University, Xiamen, Fujian, China.
Xiaoyan DuBeijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China.
Changlong LiBeijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China.
Jianyi LvBeijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China.
Xin LiuBeijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China.
Meng GuoBeijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China.
Zhenwen ChenBeijing Key Laboratory of Cancer Invasion and Metastasis Research, School of Basic Medical Sciences, Capital Medical University, Beijing, People’s Republic of China.
Capital Medical University · CNXiamen University · CN

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

In mammals, the well-organized activation of quiescent primordial follicles is pivotal for female reproductive reserve. In the present study, we examined the mechanisms underlying primordial follicle activation in mice. We found that endothelial nitric oxide synthase (eNOS) and its downstream effectors, cyclic guanosine monophosphate (cGMP) and cGMP-dependent protein kinase G (PKG), were expressed in pre-granulosa cells and promoted primordial follicle activation, oocyte growth and granulosa cell proliferation in neonatal ovaries. Mammalian target of rapamycin (mTOR) colocalized with PKG in pre-granulosa cells and was essential for eNOS/cGMP/PKG pathway-induced primordial follicle activation. The eNOS/cGMP/PKG pathway was found to stabilize mTOR protein. The mRNA levels of F-box and WD repeat domain containing 7 (FBXW7), an E3 ubiquitin ligase, correlated negatively with mTOR protein levels in neonatal ovaries. FBXW7 bound to and destabilized mTOR protein in pre-granulosa cells in a ubiquitin/proteasome-dependent manner. However, agonists of the eNOS/cGMP/PKG pathway reduced FBXW7 mRNA levels. FBXW7 overexpression suppressed primordial follicle activation and prevented the eNOS/cGMP/PKG pathway from activating primordial follicles and stabilizing mTOR protein. These findings demonstrate that the eNOS/cGMP/PKG pathway activates primordial follicles by suppressing FBXW7-induced ubiquitination of mTOR in mice.

Indexed as

AnimalsAnimals, NewbornCell ProliferationCyclic GMPCyclic GMP-Dependent Protein Kinase Type IF-Box-WD Repeat-Containing Protein 7FemaleForkhead Box Protein O3Granulosa CellsMiceNitric Oxide Synthase Type IIIOocytesOrgan Culture TechniquesOvarian FollicleOvaryProtein TransportCyclic GMPCyclic GMP-Dependent Protein Kinase Type IF-Box-WD Repeat-Containing Protein 7Fbxw7 protein, mouseForkhead Box Protein O3FoxO3 protein, mousemTOR protein, mouseNitric Oxide Synthase Type IIINos3 protein, mousePrkg1 protein, mouseTOR Serine-Threonine KinaseseNOS/cGMP/PKG pathwayFBXW7mTORprimordial follicle activationubiquitination

Identifiers

PMID33291075
PMCPMC7835019
OpenAlexW3107324133

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.