Evidence map›Paper›PMID 37294625›Full record

ArticleBiology of reproduction2023

Mitochondrial uncouplers impair human sperm motility without altering ATP content†.

Will M Skinner, Natalie T Petersen, Bret Unger, Shaogeng Tang, Emiliano Tabarsi, Julianna Lamm, Liza Jalalian, James Smith, Ambre M Bertholet, Ke Xu and 2 more

Abstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Biology of reproduction, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 2 papers.

0numbers the graph read from it
0cells of the map it votes in
2citing papers in PubMed
–field-weighted citation impact
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

2 citing papers in PubMed.

  1. Article
  2. 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

12 authors.

Will M SkinnerEndocrinology Graduate Group, University of California, Berkeley, Berkeley, California, USA.
Natalie T PetersenDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA.
Bret UngerDepartment of Chemistry, University of California, Berkeley, Berkeley, California, USA.
Shaogeng TangDepartment of Biochemistry, Stanford University School of Medicine, Stanford, California, USA.
Emiliano TabarsiDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA.
Julianna LammDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, California, USA.
Liza JalalianDepartment of Obstetrics and Gynecology, University of California, San Francisco Center for Reproductive Health, San Francisco, California, USA.
James SmithDepartment of Urology, University of California, San Francisco, San Francisco, California, USA.
Ambre M BertholetDepartment of Physiology, University of California, San Francisco, San Francisco, California, USA.
Ke XuDepartment of Chemistry, University of California, Berkeley, Berkeley, California, USA.
Yuriy KirichokDepartment of Physiology, University of California, San Francisco, San Francisco, California, USA.
Polina V LishkoEndocrinology Graduate Group, University of California, Berkeley, Berkeley, California, USA.

Funding

Molecular Biophysics of Mitochondrial MembranesR35GM136415 · NIGMS · WASHINGTON UNIVERSITY · PI Yuriy Kirichok · 2020 to 2026
$4.7M
A Zeiss Elyra S1 Structured Illumination Microscope for the Biological Imaging FaS10OD018136 · OD · UNIVERSITY OF CALIFORNIA BERKELEY · PI RUZIN, STEVEN EARL · 2014 to 2014
$600k
Cell Surface Receptor Recognition and Membrane Fusion in Mammalian FertilizationK99HD104924 · NICHD · STANFORD UNIVERSITY · PI TANG, SHAOGENG · 2021 to 2022
$383k
NICHD NIH HHS K99 HD104924NIGMS NIH HHS R35 GM136415NIH HHS S10 OD018136
6 · The paper itself

Abstract

In human spermatozoa, the electrochemical potentials across the mitochondrial and plasma membranes are related to sperm functionality and fertility, but the exact role of each potential has yet to be clarified. Impairing sperm mitochondrial function has been considered as an approach to creating male or unisex contraceptives, but it has yet to be shown whether this approach would ultimately block the ability of sperm to reach or fertilize an egg. To investigate whether the mitochondrial and plasma membrane potentials are necessary for sperm fertility, human sperm were treated with two small-molecule mitochondrial uncouplers (niclosamide ethanolamine and BAM15) that depolarize membranes by inducing passive proton flow, and evaluated the effects on a variety of sperm physiological processes. BAM15 specifically uncoupled human sperm mitochondria while niclosamide ethanolamine induced proton current in the plasma membrane in addition to depolarizing the mitochondria. In addition, both compounds significantly decreased sperm progressive motility with niclosamide ethanolamine having a more robust effect. However, these uncouplers did not reduce sperm adenosine triphosphate (ATP) content or impair other physiological processes, suggesting that human sperm can rely on glycolysis for ATP production if mitochondria are impaired. Thus, systemically delivered contraceptives that target sperm mitochondria to reduce their ATP production would likely need to be paired with sperm-specific glycolysis inhibitors. However, since niclosamide ethanolamine impairs sperm motility through an ATP-independent mechanism, and niclosamide is FDA approved and not absorbed through mucosal membranes, it could be a useful ingredient in on-demand, vaginally applied contraceptives.

Indexed as

Adenosine TriphosphateSperm MotilityContraceptive AgentsEthanolamineEthanolaminesHumansMaleMitochondriaNiclosamideProtonsSemenSpermatozoaAdenosine TriphosphateContraceptive AgentsEthanolamineEthanolaminesNiclosamideProtonscontraceptionmitochondrial uncouplerssperm metabolismsperm motility

Identifiers

PMID37294625
PMCPMC10427809

What OpenQuestion holds

Textmetadata
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.