RNA N6-methyladenosine modification in female reproductive biology and pathophysiology

Huang, Erqing; Chen, Lijuan

doi:10.1186/s12964-023-01078-4

Cited by 8 publications

(6 citation statements)

References 175 publications

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“…The aforementioned results have highlighted the beneficial effects of Que@MOF/Man on inflammatory macrophages. Considering the pivotal role of macrophage‐cardiomyocyte communication in the progression of cardiovascular disease, [ 43 ] we thus investigated the effect of Que@MOF/Man‐treated macrophages on cardiomyocytes. To mimic the MI microenvironment in vitro, LPS‐induced RAW 264.7 cells and H 2 O 2 ‐induced H9C2 cells were co‐cultured ( Figure 6 A ).…”

Section: Resultsmentioning

confidence: 99%

Inflammation‐Targeted Nanomedicines Alleviate Oxidative Stress and Reprogram Macrophages Polarization for Myocardial Infarction Treatment

Hu,

Li,

et al. 2024

Advanced Science

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Myocardial infarction (MI) is a critical global health challenge, with current treatments limited by the complex MI microenvironment, particularly the excessive oxidative stress and intense inflammatory responses that exacerbate cardiac dysfunction and MI progression. Herein, a mannan‐based nanomedicine, Que@MOF/Man, is developed to target the inflammatory infarcted heart and deliver the antioxidative and anti‐inflammatory agent quercetin (Que), thereby facilitating a beneficial myocardial microenvironment for cardiac repair. The presence of mannan on the nanoparticle surface enables selective internalization by macrophages rather than cardiomyocytes. Que@MOF/Man effectively neutralizes reactive oxygen species in macrophages to reduce oxidative stress and promote their differentiation into a reparative phenotype, reconciling the inflammatory response and enhancing cardiomyocyte survival through intercellular communication. Owing to the recruitment of macrophages into inflamed myocardium post‐MI, in vivo, administration of Que@MOF/Man in MI rats revealed the specific distribution into the injured myocardium compared to free Que. Furthermore, Que@MOF/Man exhibited favorable results in resolving inflammation and protecting cardiomyocytes, thereby preventing further myocardial remodeling and improving cardiac function in MI rats. These findings collectively validate the rational design of an inflammation‐targeted delivery strategy to mitigate oxidative stress and modulate the inflammation response in the injured heart, presenting a therapeutic avenue for MI treatment.

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Section: Resultsmentioning

confidence: 99%

Inflammation‐Targeted Nanomedicines Alleviate Oxidative Stress and Reprogram Macrophages Polarization for Myocardial Infarction Treatment

Hu,

Li,

et al. 2024

Advanced Science

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“…The M6A modification, the most common type of RNA modification, is involved in many important physiological and pathological processes in the reproductive system [ 47 , 48 ]. It also plays an important role in premature ovarian failure and PCOS [ 49 , 50 ].…”

Section: Discussionmentioning

confidence: 99%

Short-chain fatty acid-butyric acid ameliorates granulosa cells inflammation through regulating METTL3-mediated N6-methyladenosine modification of FOSL2 in polycystic ovarian syndrome

Liu

Huang

et al. 2023

Clin Epigenet

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Polycystic ovary syndrome (PCOS) is an endocrine and metabolic disorder characterized by chronic low-grade inflammation. Previous studies have demonstrated that the gut microbiome can affect the host tissue cells’ mRNA N6-methyladenosine (m6A) modifications. This study aimed to understand the role of intestinal flora in ovarian cells inflammation by regulating mRNA m6A modification particularly the inflammatory state in PCOS. The gut microbiome composition of PCOS and Control groups was analyzed by 16S rRNA sequencing, and the short chain fatty acids were detected in patients’ serum by mass spectrometry methods. The level of butyric acid was found to be decreased in the serum of the obese PCOS group (FAT) compared to other groups, and this was correlated with increased Streptococcaceae and decreased Rikenellaceae based on the Spearman’s rank test. Additionally, we identified FOSL2 as a potential METTL3 target using RNA-seq and MeRIP-seq methodologies. Cellular experiments demonstrated that the addition of butyric acid led to a decrease in FOSL2 m6A methylation levels and mRNA expression by suppressing the expression of METTL3, an m6A methyltransferase. Additionally, NLRP3 protein expression and the expression of inflammatory cytokines (IL-6 and TNF-α) were downregulated in KGN cells. Butyric acid supplementation in obese PCOS mice improved ovarian function and decreased the expression of local inflammatory factors in the ovary. Taken together, the correlation between the gut microbiome and PCOS may unveil crucial mechanisms for the role of specific gut microbiota in the pathogenesis of PCOS. Furthermore, butyric acid may present new prospects for future PCOS treatments.

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“…Some of these adaptations appear to be manifested by epigenetic modifications [130][131][132][133][134][135]. However, some long-term epigenetic modifications may also contribute to adverse risks of pregnancy leading to pathological responses [136,137], but others appear to be transient and reversed during the postpartum period [131].…”

Section: During Pregnancy and Lactationmentioning

confidence: 99%

The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

Hart

2024

IJMS

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For much of human evolution, the average lifespan was <40 years, due in part to disease, infant mortality, predators, food insecurity, and, for females, complications of childbirth. Thus, for much of evolution, many females did not reach the age of menopause (45–50 years of age) and it is mainly in the past several hundred years that the lifespan has been extended to >75 years, primarily due to public health advances, medical interventions, antibiotics, and nutrition. Therefore, the underlying biological mechanisms responsible for disease risk following menopause must have evolved during the complex processes leading to Homo sapiens to serve functions in the pre-menopausal state. Furthermore, as a primary function for the survival of the species is effective reproduction, it is likely that most of the advantages of having such post-menopausal risks relate to reproduction and the ability to address environmental stresses. This opinion/perspective will be discussed in the context of how such post-menopausal risks could enhance reproduction, with improved survival of offspring, and perhaps why such risks are preserved. Not all post-menopausal females exhibit risk for this set of diseases, and those who do develop such diseases do not have all of the conditions. The diseases of the post-menopausal state do not operate as a unified complex, but as independent variables, with the potential for some overlap. The how and why there would be such heterogeneity if the risk factors serve essential functions during the reproductive years is also discussed and the concept of sets of reversible epigenetic changes associated with puberty, pregnancy, and lactation is offered to explain the observations regarding the distribution of post-menopausal conditions and their potential roles in reproduction. While the involvement of an epigenetic system with a dynamic “modification-demodification-remodification” paradigm contributing to disease risk is a hypothesis at this point, validation of it could lead to a better understanding of post-menopausal disease risk in the context of reproduction with commonalities may also lead to future improved interventions to control such risk after menopause.

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RNA N6-methyladenosine modification in female reproductive biology and pathophysiology

Cited by 8 publications

References 175 publications

Inflammation‐Targeted Nanomedicines Alleviate Oxidative Stress and Reprogram Macrophages Polarization for Myocardial Infarction Treatment

Inflammation‐Targeted Nanomedicines Alleviate Oxidative Stress and Reprogram Macrophages Polarization for Myocardial Infarction Treatment

Short-chain fatty acid-butyric acid ameliorates granulosa cells inflammation through regulating METTL3-mediated N6-methyladenosine modification of FOSL2 in polycystic ovarian syndrome

The Heterogeneity of Post-Menopausal Disease Risk: Could the Basis for Why Only Subsets of Females Are Affected Be Due to a Reversible Epigenetic Modification System Associated with Puberty, Menstrual Cycles, Pregnancy and Lactation, and, Ultimately, Menopause?

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