Nicotinamide mononucleotide improves spermatogenesis in aluminium-exposed mice by inhibiting NLRP3-mediated pyroptosis.

Nong W, Huang Q, Dou S, Wei Y, Song Y, Wang J, Lei X, Yang F, He L

PloS one22 Jan 2026Cited by 1 (Europe PMC)

PMID41569982PMCIDPMC12826483DOI10.1371/journal.pone.0339020PepBankPUB-41569982

Summary

This study investigates the protective effects of nicotinamide mononucleotide (NMN) against aluminum-induced testicular dysfunction in mice. While previous research has demonstrated the general protective role of NMN in testicular function and highlighted the interaction between aluminum and the NLRP3 inflammasome, the precise mechanisms through which NMN mitigates aluminum-induced reproductive toxicity remain unclear. Our findings show that NMN protects Sertoli cells by inhibiting NLRP3-mediated pyroptosis, which subsequently improves spermatogenesis and testosterone synthesis. We also identify WT1 and GATA4 as key regulators involved in maintaining Sertoli cell integrity and function under aluminum-induced stress. This work provides new insights into the molecular mechanisms of aluminum-induced male infertility and underscores NMN's potential as a therapeutic strategy for preventing reproductive dysfunction caused by environmental toxicants, such as aluminum. Aluminum exposure disrupts spermatogenesis, yet no effective pharmacological interventions exist to treat aluminum-induced male infertility. In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels. Hematoxylin and eosin (H&E) staining revealed significant damage, including reduced seminiferous tubule diameter, disorganized germ cell layers, and a decreased number of germ cells and sperm. Sperm motility was significantly reduced, while the proportion of abnormal sperm increased. However, NMN treatment partially reversed these impairments. Transcriptomic analysis revealed significant upregulation of genes involved in the NLRP3 inflammasome and apoptosis pathways (e.g., NLRP3, GSDMD, caspase-1, and IL-1β) in the AlCl3-exposed group. NMN treatment mitigated testicular damage, suppressed NLRP3-mediated pyroptosis in Sertoli cells, and restored serum testosterone levels. Additionally, NMN treatment preserved the expression of key testicular proteins, including WT-1 GATA4, and vimentin. In summary, our study uncovers a novel mechanism by which aluminum exposure impairs spermatogenesis via NLRP3-mediated pyroptosis in testicular cells. We also demonstrate for the first time that NMN can ameliorate aluminum-induced reproductive dysfunction by inhibiting this pathway, offering a potential therapeutic strategy for aluminum-associated male infertility.

CC BYText from Europe PMC. Highlighted sentences are the source of results.

Results from this study14

14 results from studies that gave the peptide. No result from this study comes from people.

01AnimalAnimal study (in vivo)Efficacy outcome
In aluminum-exposed mice, NMN improved spermatogenesis.
In plain wordsIn mice exposed to aluminum, NMN improved sperm production.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseSpermatogenesis
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Our findings show that NMN protects Sertoli cells by inhibiting NLRP3-mediated pyroptosis, which subsequently improves spermatogenesis and testosterone synthesis.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998201
02AnimalAnimal study (in vivo)Efficacy outcome
In aluminum-exposed mice, NMN improved testosterone synthesis.
In plain wordsIn mice exposed to aluminum, NMN improved testosterone production.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseTestosterone synthesis
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Our findings show that NMN protects Sertoli cells by inhibiting NLRP3-mediated pyroptosis, which subsequently improves spermatogenesis and testosterone synthesis.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998202
03AnimalAnimal study (in vivo)Efficacy outcome
In aluminum-exposed mice, NMN partially reversed the reduction in seminiferous tubule diameter.
In plain wordsIn mice exposed to aluminum, NMN partially restored sperm-producing tubule diameter.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseSeminiferous tubule diameter
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
However, NMN treatment partially reversed these impairments.
2 context sentences(design, population, supporting numbers)
Summary · context
Hematoxylin and eosin (H&E) staining revealed significant damage, including reduced seminiferous tubule diameter, disorganized germ cell layers, and a decreased number of germ cells and sperm.
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998203
04AnimalAnimal study (in vivo)Efficacy outcome
In aluminum-exposed mice, NMN partially reversed germ cell layer disorganization.
In plain wordsIn mice exposed to aluminum, NMN partially restored the organization of sperm-producing cell layers.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
MixedGerm cell layer organization
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
However, NMN treatment partially reversed these impairments.
2 context sentences(design, population, supporting numbers)
Summary · context
Hematoxylin and eosin (H&E) staining revealed significant damage, including reduced seminiferous tubule diameter, disorganized germ cell layers, and a decreased number of germ cells and sperm.
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998204
05AnimalAnimal study (in vivo)Efficacy outcome
In aluminum-exposed mice, NMN partially reversed the reduction in germ cell number.
In plain wordsIn mice exposed to aluminum, NMN partially restored germ cell numbers.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseGerm cell number
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
However, NMN treatment partially reversed these impairments.
2 context sentences(design, population, supporting numbers)
Summary · context
Hematoxylin and eosin (H&E) staining revealed significant damage, including reduced seminiferous tubule diameter, disorganized germ cell layers, and a decreased number of germ cells and sperm.
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998205
06AnimalAnimal study (in vivo)Efficacy outcome
In aluminum-exposed mice, NMN partially reversed the reduction in sperm number.
In plain wordsIn mice exposed to aluminum, NMN partially restored sperm numbers.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseSperm number
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
However, NMN treatment partially reversed these impairments.
2 context sentences(design, population, supporting numbers)
Summary · context
Hematoxylin and eosin (H&E) staining revealed significant damage, including reduced seminiferous tubule diameter, disorganized germ cell layers, and a decreased number of germ cells and sperm.
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998206
07AnimalAnimal study (in vivo)Efficacy outcome
In aluminum-exposed mice, NMN partially reversed impaired sperm motility.
In plain wordsIn mice exposed to aluminum, NMN partially restored sperm movement.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseSperm motility
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
However, NMN treatment partially reversed these impairments.
2 context sentences(design, population, supporting numbers)
Summary · context
Sperm motility was significantly reduced, while the proportion of abnormal sperm increased.
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998207
08AnimalAnimal study (in vivo)Efficacy outcome
In aluminum-exposed mice, NMN partially reversed the increase in abnormal sperm proportion.
In plain wordsIn mice exposed to aluminum, NMN partially reduced the increased proportion of abnormal sperm.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseAbnormal sperm proportion
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
However, NMN treatment partially reversed these impairments.
2 context sentences(design, population, supporting numbers)
Summary · context
Sperm motility was significantly reduced, while the proportion of abnormal sperm increased.
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998208
09AnimalAnimal study (in vivo)Efficacy outcome
In aluminum-exposed mice, NMN mitigated testicular damage.
In plain wordsIn mice exposed to aluminum, NMN reduced testicular damage.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseTesticular damage
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
NMN treatment mitigated testicular damage, suppressed NLRP3-mediated pyroptosis in Sertoli cells, and restored serum testosterone levels.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998209
10AnimalAnimal study (in vivo)Mechanism
In aluminum-exposed mice, NMN suppressed NLRP3-mediated Sertoli cell pyroptosis.
In plain wordsIn mice exposed to aluminum, NMN reduced inflammatory death of cells that support sperm production.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
DecreaseSertoli cell pyroptosis
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
NMN treatment mitigated testicular damage, suppressed NLRP3-mediated pyroptosis in Sertoli cells, and restored serum testosterone levels.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998210
11AnimalAnimal study (in vivo)Efficacy outcome
In aluminum-exposed mice, NMN restored serum testosterone levels.
In plain wordsIn mice exposed to aluminum, NMN restored blood testosterone levels.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
IncreaseSerum testosterone
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Sex hormones and fertility · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
NMN treatment mitigated testicular damage, suppressed NLRP3-mediated pyroptosis in Sertoli cells, and restored serum testosterone levels.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998211
12AnimalAnimal study (in vivo)Mechanism
In aluminum-exposed mice, NMN preserved testicular WT-1 expression.
In plain wordsIn mice exposed to aluminum, NMN preserved testicular WT-1 protein expression.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
MixedWT-1 expression
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Additionally, NMN treatment preserved the expression of key testicular proteins, including WT-1 GATA4, and vimentin.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998212
13AnimalAnimal study (in vivo)Mechanism
In aluminum-exposed mice, NMN preserved testicular GATA4 expression.
In plain wordsIn mice exposed to aluminum, NMN preserved testicular GATA4 protein expression.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
MixedGATA4 expression
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Additionally, NMN treatment preserved the expression of key testicular proteins, including WT-1 GATA4, and vimentin.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998213
14AnimalAnimal study (in vivo)Mechanism
In aluminum-exposed mice, NMN preserved testicular vimentin expression.
In plain wordsIn mice exposed to aluminum, NMN preserved testicular vimentin protein expression.
Peptide
NMN (nicotinamide mononucleotide)
Outcome
MixedVimentin expression
Study
mousen: not reported in source
AlCl3-exposed C57BL/6J mice
Outcome group
Receptor activity and mechanism · Reproductive and sexual health
Studied dose
Dose not stated
Source sentences
Summary
Additionally, NMN treatment preserved the expression of key testicular proteins, including WT-1 GATA4, and vimentin.
1 context sentence(design, population, supporting numbers)
Summary · context
In this study, we established an aluminum toxicity model in C57BL/6J mice through intragastric administration of AlCl3. We assessed the therapeutic effects of NMN by evaluating testicular histopathology, sperm quality, and serum reproductive hormone levels.
Show in the study text Report a problemFND-4156998214

AI wrote and checked these results. AI can make mistakes, so check important results against the source.

Version history

PepBank keeps every version of the data on this study. Status changes from Retraction Watch, Europe PMC and Crossref are listed with their source.

Version 2Current
21 Oct 2026, 15:58 UTC
Study results updated
Version 1
21 Oct 2026, 12:50 UTC
First added · source update from Europe PMC

Subjects

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