Evidence map›Paper›PMID 26678449›Full record

ArticleFASEB journal : official publication of the Federation of American Societies for Experimental Biology2016

Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.

Nan Li, Dolores D Mruk, Ka-Wai Mok, Michelle W M Li, Chris K C Wong, Will M Lee, Daishu Han, Bruno Silvestrini, C Yan Cheng

Open access · greenAbstract read
In one paragraph

Article in FASEB journal : official publication of the Federation of American Societies for Experimental Biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 24 papers.

0numbers the graph read from it
0cells of the map it votes in
24citing papers in PubMed
2.1field-weighted citation impact, top 12% 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

24 citing papers in PubMed, 46 citations in OpenAlex.

  1. Review
  2. Article
  3. Review
  4. Article
  5. Testis Toxicants: Lesson from Traditional Chinese Medicine (TCM).Advances in experimental medicine and biology · 2021
    Article
  6. Microtubule Cytoskeleton and Spermatogenesis-Lesson From Studies of Toxicant Models.Toxicological sciences : an official journal of the Society of Toxicology · 2020
    Review
  7. Article
  8. Article
  9. Article
  10. Article
  11. Article
  12. Article
  13. Article
  14. Dynein 1 supports spermatid transport and spermiation during spermatogenesis in the rat testis.American journal of physiology. Endocrinology and metabolism · 2018
    Article
  15. Review
  16. TheBiology open · 2018
    Article
  17. Article
  18. Article
  19. Article
  20. 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

9 authors at 6 institutions in 5 countries.

Nan Li*The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA; Department of Biology, Hong Kong Baptist University, Hong Kong, China; School of Biological Sciences, University of Hong Kong, Hong Kong, China; Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; and S.B.M. Srl Pharmaceuticals, Rome, Italy.
Dolores D Mruk*The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA; Department of Biology, Hong Kong Baptist University, Hong Kong, China; School of Biological Sciences, University of Hong Kong, Hong Kong, China; Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; and S.B.M. Srl Pharmaceuticals, Rome, Italy.
Ka-Wai Mok*The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA; Department of Biology, Hong Kong Baptist University, Hong Kong, China; School of Biological Sciences, University of Hong Kong, Hong Kong, China; Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; and S.B.M. Srl Pharmaceuticals, Rome, Italy.
Michelle W M Li*The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA; Department of Biology, Hong Kong Baptist University, Hong Kong, China; School of Biological Sciences, University of Hong Kong, Hong Kong, China; Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; and S.B.M. Srl Pharmaceuticals, Rome, Italy.
Chris K C Wong*The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA; Department of Biology, Hong Kong Baptist University, Hong Kong, China; School of Biological Sciences, University of Hong Kong, Hong Kong, China; Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; and S.B.M. Srl Pharmaceuticals, Rome, Italy.
Will M Lee*The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA; Department of Biology, Hong Kong Baptist University, Hong Kong, China; School of Biological Sciences, University of Hong Kong, Hong Kong, China; Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; and S.B.M. Srl Pharmaceuticals, Rome, Italy.
Daishu Han*The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA; Department of Biology, Hong Kong Baptist University, Hong Kong, China; School of Biological Sciences, University of Hong Kong, Hong Kong, China; Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; and S.B.M. Srl Pharmaceuticals, Rome, Italy.
Bruno Silvestrini*The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA; Department of Biology, Hong Kong Baptist University, Hong Kong, China; School of Biological Sciences, University of Hong Kong, Hong Kong, China; Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; and S.B.M. Srl Pharmaceuticals, Rome, Italy.
C Yan Cheng*The Mary M. Wohlford Laboratory for Male Contraceptive Research, Center for Biomedical Research, Population Council, New York, New York, USA; Department of Biology, Hong Kong Baptist University, Hong Kong, China; School of Biological Sciences, University of Hong Kong, Hong Kong, China; Department of Cell Biology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences, Peking Union Medical College, Beijing, China; and S.B.M. Srl Pharmaceuticals, Rome, Italy y-cheng@popcbr.rockefeller.edu ccheng@mail.rockefeller.edu.
Population Council · INChinese Academy of Medical Sciences & Peking Union Medical College · CNHong Kong Baptist University · HKNewron Pharmaceuticals (Italy) · ITPopulation Council · USUniversity of Hong Kong · HK

Funding

SPECIALIZED CONTRACEPTIVE DEVELOPMENT RESEARCH CENTERU54HD029990 · NICHD · POPULATION COUNCIL · PI WARE, REGINE SITRUK · 1992 to 2016
$27.7M
The biology of blood-testis barrier dynamicsR01HD056034 · NICHD · POPULATION COUNCIL · PI CHENG, C. YAN · 2009 to 2018
$3.4M
NICHD NIH HHS R01 HD056034NICHD NIH HHS R01-HD056034NICHD NIH HHS U54 HD029990NICHD NIH HHS U54-HD029990
6 · The paper itself

Abstract

Earlier studies have shown that rats treated with an acute dose of 1-(2,4-dichlorobenzyl)-1H-indazole-3-carbohydrazide (adjudin, a male contraceptive under development) causes permanent infertility due to irreversible blood-testis barrier (BTB) disruption even though the population of undifferentiated spermatogonia remains similar to normal rat testes, because spermatogonia fail to differentiate into spermatocytes to enter meiosis. Since other studies have illustrated the significance of connexin 43 (Cx43)-based gap junction in maintaining the homeostasis of BTB in the rat testis and the phenotypes of Sertoli cell-conditional Cx43 knockout mice share many of the similarities of the adjudin-treated rats, we sought to examine if overexpression of Cx43 in these adjudin-treated rats would reseal the disrupted BTB and reinitiate spermatogenesis. A full-length Cx43 cloned into mammalian expression vector pCI-neo was used to transfect testes of adjudin-treated ratsversusempty vector. It was found that overexpression of Cx43 indeed resealed the Sertoli cell tight junction-permeability barrier based on a functionalin vivoassay in tubules displaying signs of meiosis as noted by the presence of round spermatids. Thus, these findings suggest that overexpression of Cx43 reinitiated spermatogenesis at least through the steps of meiosis to generate round spermatids in testes of rats treated with an acute dose of adjudin that led to aspermatogenesis. It was also noted that the round spermatids underwent eventual degeneration with the formation of multinucleated cells following Cx43 overexpression due to the failure of spermiogenesis because no elongating/elongated spermatids were detected in any of the tubules examined. The mechanism by which overexpression of Cx43 reboots meiosis and rescues BTB function was also examined. In summary, overexpression of Cx43 in the testis with aspermatogenesis reboots meiosis and reseals toxicant-induced BTB disruption, even though it fails to support round spermatids to enter spermiogenesis.-Li, N., Mruk, D. D., Mok, K.-W., Li, M. W. M., Wong, C. K. C., Lee, W. M., Han, D., Silvestrini, B., Cheng, C. Y. Connexin 43 reboots meiosis and reseals blood-testis barrier following toxicant-mediated aspermatogenesis and barrier disruption.

Indexed as

AnimalsBlood-Testis BarrierConnexin 43Gene ExpressionHydrazinesImmunoblottingIndazolesMaleMeiosisMice, KnockoutMicroscopy, FluorescenceRats, Sprague-DawleyReverse Transcriptase Polymerase Chain ReactionSertoli CellsSpermatidsSpermatogenesis1-(2,4-dichlorobenzyl)indazole-3-carbohydrazideConnexin 43HydrazinesIndazolesactin microfilamentsgap junctionseminiferous epithelial cyclespermatogenesistight junction

Identifiers

PMID26678449
PMCPMC4799501
OpenAlexW2256128974

What OpenQuestion holds

Textmetadata
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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.