Evidence map›Paper›PMID 21441423›Full record

ReviewJournal of andrology

Establishment of cell-cell cross talk in the epididymis: control of luminal acidification.

Winnie W C Shum, Ye Chun Ruan, Nicolas Da Silva, Sylvie Breton

Open access · greenAbstract readReview
In one paragraph

Review in Journal of andrology. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.

0numbers the graph read from it
0cells of the map it votes in
73citing papers in PubMed
9.6field-weighted citation impact, top 2% 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

73 citing papers in PubMed, 119 citations in OpenAlex.

  1. Article
  2. Article
  3. Article
  4. Article
  5. Review
  6. Article
  7. Metabolomic Analysis of Cauda Epididymal Fluid in Yaks and Cattle.Animals : an open access journal from MDPI · 2025
    Article
  8. Article
  9. Article
  10. Epididymal-Born circRNA Cargo and Its Implications in Male Fertility.International journal of molecular sciences · 2025
    Review
  11. Review
  12. Review
  13. Article
  14. Article
  15. Article
  16. Article
  17. Article
  18. Article
  19. Article
  20. Article

13 more citing papers are in PubMed but not listed here.

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

4 authors at 3 institutions in 1 country.

Winnie W C ShumProgram in Membrane Biology, MGH Simches Research Center, 185 Cambridge Street, Boston, MA 02114, USA.
Ye Chun Ruan
Nicolas Da Silva
Sylvie Breton
Harvard University · USCenter for Systems Biology · USMassachusetts General Hospital · US

Funding

Pilot & Feasibility ProgramP30DK043351 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI RAYMOND T CHUNG · 1991 to 2026
$35.3M
Transgenic CoreP30DK057521 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI FLOREZ, JOSE CARLOS · 2000 to 2019
$31.4M
SIGNALLING IN MESANGIAL CELLS--CALCIUM AND PHOPHOLIPASESP01DK038452 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BROWN, DENNIS · 1987 to 2012
$20.1M
Transfer of grant 5R01HD040793 - Intercellular networks and luminal acidification in the male reproductive tractR01HD040793 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI BRETON, SYLVIE · 2001 to 2021
$6.6M
3-Dimensional modeling of basal cell function in pseudostratified epitheliaR01DK085715 · NIDDK · MASSACHUSETTS GENERAL HOSPITAL · PI BRETON, SYLVIE · 2009 to 2013
$2.7M
Water and solute transport in the epididymisR01HD045821 · NICHD · MASSACHUSETTS GENERAL HOSPITAL · PI BRETON, SYLVIE · 2006 to 2010
$1.7M
NICHD NIH HHS HD040793NICHD NIH HHS HD045821NICHD NIH HHS R01 HD040793NICHD NIH HHS R01 HD045821NIDDK NIH HHS DK038452NIDDK NIH HHS DK085715NIDDK NIH HHS DK43351NIDDK NIH HHS DK57521NIDDK NIH HHS P01 DK038452NIDDK NIH HHS P30 DK043351NIDDK NIH HHS P30 DK057521NIDDK NIH HHS R01 DK085715
6 · The paper itself

Abstract

Male infertility is often caused by sperm that have low motility and interact poorly with the oocyte. Spermatozoa acquire these crucial functions in the epididymis. A low luminal bicarbonate (HCO(3)(-)) concentration and low pH keep sperm quiescent during their maturation and storage in this organ. This review describes how epididymal epithelial cells work in a concerted manner, together with spermatozoa, to establish and maintain this acidic luminal environment. Clear cells express the proton-pumping ATPase (V-ATPase) in their apical membrane and actively secrete protons. HCO(3)(-) induces V-ATPase accumulation in apical microvilli in clear cells via HCO(3)(-)-sensitive adenylyl cyclase-dependent cAMP production. HCO(3)(-) is secreted from principal cells following basolateral stimulation, to transiently "prime" spermatozoa before ejaculation. Luminal ATP and adenosine also induce V-ATPase apical accumulation in clear cells via activation of P2 and P1 receptors, respectively. ATP is released into the lumen from sperm and principal cells and is then metabolized into adenosine by local nucleotidases. In addition, the V-ATPase is regulated by luminal angiotensin II via activation of basal cells, which can extend narrow body projections that cross the tight junction barrier. Basal cells then secrete nitric oxide, which diffuses out to stimulate proton secretion in clear cells via activation of the cGMP pathway. Thus, an elaborate communication network is present between principal cells and clear cells, and between basal cells and clear cells, to control luminal acidification. Monitoring and decoding these "intercellular conversations" will help define pathophysiologic mechanisms underlying male infertility.

Indexed as

Cell CommunicationAdenosineAdenosine TriphosphateAngiotensin IIAnimalsBicarbonatesCyclic GMPEpididymisHumansMaleMiceNitric OxideRatsReceptors, PurinergicSpermatozoaTight JunctionsAdenosineAdenosine TriphosphateAngiotensin IIBicarbonatesCyclic GMPNitric OxideReceptors, PurinergicVacuolar Proton-Translocating ATPases

Identifiers

PMID21441423
PMCPMC3753098
OpenAlexW2039738224

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.