Melatonin alleviates high temperature exposure induced fetal growth restriction via the gut-placenta-fetus axis in pregnant mice
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Study information
-
Quality control
- Retracted paper
- Contamination issues suspected
- Batch effect issues suspected
- Uncontrolled confounding suspected
- Results are suspect (various reasons)
- Tags applied
study design
Citation
PMID PubMed identifier for scientific articles.
DOI Digital object identifier for electronic documents.
Authors
Wu JJ, Zheng X, Wu C, Ma W, Wang Y, Wang J, Wei Y, Zeng X, Zhang S, Guan W, Chen F
Journal
Journal of advanced research
Year
2025
Keywords:
Gut microbial dysbiosis, Heat stress, LPS, Melatonin administration, Placental barrier
INTRODUCTION: Global warming augments the risk of adverse pregnancy outcomes in vulnerable expectant mothers. Pioneering investigations into heat stress (HS) have predominantly centered on its direct impact on reproductive functions, while the potential roles of gut microbiota, despite its significant influence on distant tissues, remain largely unexplored. Our understanding of deleterious mechanisms of HS and the development of effective intervention strategies to mitigate the detrimental impacts are still limited. OBJECTIVES: In this study, we aimed to explore the mechanisms by which melatonin targets gut microbes to alleviate HS-induced reproductive impairment. METHODS: We firstly evaluated the alleviating effects of melatonin supplementation on HS-induced reproductive disorder in pregnant mice. Microbial elimination and fecal microbiota transplantation (FMT) experiments were then conducted to confirm the efficacy of melatonin through regulating gut microbiota. Finally, a lipopolysaccharide (LPS)-challenged experiment was performed to verify the mechanism by which melatonin alleviates HS-induced reproductive impairment. RESULTS: Melatonin supplementation reinstated gut microbiota in heat stressed pregnant mice, reducing LPS-producing bacteria (Aliivibrio) and increasing beneficial butyrate-producing microflora (Butyricimonas). This restoration corresponded to decreased LPS along the maternal gut-placenta-fetus axis, accompanied by enhanced intestinal and placental barrier integrity, safeguarding fetuses from oxidative stress and inflammation, and ultimately improving fetal weight. Further pseudo-sterile and fecal microbiota transplantation trials confirmed that the protective effect of melatonin on fetal intrauterine growth under HS was partially dependent on gut microbiota. In LPS-challenged pregnant mice, melatonin administration mitigated placental barrier injury and abnormal angiogenesis via the inactivation of the TLR4/MAPK/VEGF signaling pathway, ultimately leading to enhanced nutrient transportation in the placenta and thereby improving the fetal weight. CONCLUSION: Melatonin alleviates HS-induced low fetal weight during pregnancy via the gut-placenta-fetus axis, the first time highlighting the gut microbiota as a novel intervention target to mitigate the detrimental impact of global temperature rise on vulnerable populations.
Experiment 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Subjects
- Location of subjects
- China
- Host species Species from which microbiome was sampled. Contact us to have more species added.
- Mus musculus
- Body site Anatomical site where microbial samples were extracted from according to the Uber Anatomy Ontology
- Cecum mucosa Caecum mucosa,Caecum mucosa of organ,Caecum mucous membrane,Caecum organ mucosa,Cecal mucosa,Cecum mucosa of organ,Cecum mucous membrane,Cecum organ mucosa,Intestinum crassum caecum mucosa,Intestinum crassum caecum mucosa of organ,Intestinum crassum caecum mucous membrane,Intestinum crassum caecum organ mucosa,Mucosa of caecum,Mucosa of cecum,Mucosa of intestinum crassum caecum,Mucosa of organ of caecum,Mucosa of organ of cecum,Mucosa of organ of intestinum crassum caecum,Mucous membrane of caecum,Mucous membrane of cecum,Mucous membrane of intestinum crassum caecum,Organ mucosa of caecum,Organ mucosa of cecum,Organ mucosa of intestinum crassum caecum,Cecum mucosa,cecum mucosa
- Condition The experimental condition / phenotype studied according to the Experimental Factor Ontology
- Fetal growth restriction FET GROWTH RET 2500+G,FET GROWTH RET 500-749G,FET GROWTH RET 750-999G,FET GROWTH RETARD <500G,FET GROWTH RETARD WTNOS,FET GRWTH RET 1000-1249G,FET GRWTH RET 1250-1499G,FET GRWTH RET 1500-1749G,FET GRWTH RET 1750-1999G,FET GRWTH RET 2000-2499G,fetal growth restriction,Fetal Growth Retardation,fetal Growth retardation,fetal growth retardation,Fetal growth retardation (disorder),Fetal growth retardation NOS,Fetal growth retardation NOS (disorder),Fetal growth retardation, NOS,Fetal growth retardation, unspecified,Fetal growth retardation, unspecified [weight],Fetal growth retardation, unspecified, 1,000-1,249 grams,Fetal growth retardation, unspecified, 1,250-1,499 grams,Fetal growth retardation, unspecified, 1,500-1,749 grams,Fetal growth retardation, unspecified, 1,750-1,999 grams,Fetal growth retardation, unspecified, 2,000-2,499 grams,Fetal growth retardation, unspecified, 2,500+ grams,Fetal growth retardation, unspecified, 500-749 grams,Fetal growth retardation, unspecified, 750-999 grams,Fetal growth retardation, unspecified, less than 500 grams,fetal SGA,fetal small for gestational Age,fetus small for gestational Age,FGR - Fetal growth retardation,Foetal growth retardation, NOS,intrauterine Growth restriction,Intrauterine growth retardation,intrauterine Growth retardation,Intrauterine growth retardation, NOS,IUGR,IUGR - Intrauterine growth retardation,Microsomia,Microsomic baby,Poor fetal growth,Poor fetal growth state,Fetal growth restriction
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Control + Heat Stress (Con + HS)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Heat Stress + Melatonin Administration (Hs + Mel)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Pregnant mice were exposed to heat stress (HS) and supplemented with melatonin (Mel).
- Group 0 sample size Number of subjects in the control (unexposed) group
- 17
- Group 1 sample size Number of subjects in the case (exposed) group
- 10
Lab analysis
- Sequencing type
- 16S
- 16S variable region One or more hypervariable region(s) of the bacterial 16S gene
- V3-V4
Statistical Analysis
- Data transformation Data transformation applied to microbial abundance measurements prior to differential abundance testing (if any).
- relative abundances
- Statistical test
- LEfSe
- Significance threshold p-value or FDR threshold used for differential abundance testing (if any)
- 0.05
- MHT correction Have statistical tests be corrected for multiple hypothesis testing (MHT)?
- No
- LDA Score above Threshold for the linear discriminant analysis (LDA) score for studies using the popular LEfSe tool
- 2.5
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Source: Fig 3E
Description: The cladogram representation (D) and LDA score bar (E) show that bacterial taxa differed significantly among different treated groups by analysing LEfSe.
Abundance in Group 1: increased abundance in Heat Stress + Melatonin Administration (Hs + Mel)
Revision editor(s): Shulamite, KateRasheed
Experiment 2
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Control + Heat Stress + Melatonin Administration (Con + HS +Mel)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Heat Stress. (HS)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Heat Stress
- Group 0 sample size Number of subjects in the control (unexposed) group
- 18
- Group 1 sample size Number of subjects in the case (exposed) group
- 9
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Source: Fig 3E
Description: The cladogram representation (D) and LDA score bar (E) show that bacterial taxa differed significantly among different treated groups by performing the analysis of LEfSe.
Abundance in Group 1: increased abundance in Heat Stress. (HS)
Revision editor(s): Shulamite, KateRasheed
Experiment 3
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Differences from previous experiment shown
Subjects
- Group 0 name Corresponds to the control (unexposed) group for case-control studies
- Heat Stress, Heat Stress + Melatonin Administration. (HS, HS + Mel)
- Group 1 name Corresponds to the case (exposed) group for case-control studies
- Control. (Con)
- Group 1 definition Diagnostic criteria applied to define the specific condition / phenotype represented in the case (exposed) group
- Mice in the Con group were maintained under 25 ± 2 °C.
- Group 0 sample size Number of subjects in the control (unexposed) group
- 19
- Group 1 sample size Number of subjects in the case (exposed) group
- 8
Lab analysis
Statistical Analysis
Signature 1
Reviewed Marked as Reviewed by Svetlana up on 2025-4-1
Source: Fig 3E
Description: The cladogram representation (D) and LDA score bar (E) show that bacterial taxa differed significantly among different treated groups by performing the analysis of LEfSe.
Abundance in Group 1: increased abundance in Control. (Con)
Revision editor(s): Shulamite, KateRasheed
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