The role of advanced glycation end products in human infertility

Zhu, Jingling; Cai, Ya-qin; Long, Shuang-lian; Chen, Zhuo; Zhang, Mo

doi:10.1016/j.lfs.2020.117830

Cited by 27 publications

(12 citation statements)

References 101 publications

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“…Excessive AGE formation along with its toxicity in diabetes mellitus is considered a potential mechanism linking diabetes with other metabolic disorders (10). In addition to diabetes and metabolic syndrome (11), AGEs have been shown to be involved in the pathogenesis of a variety of other diseases, including neurodegeneration (12), cancer (13), osteoporosis (14), infertility (15), chronic kidney disease (16) and aging (17,18). Correspondingly, the results of a recent meta-analysis demonstrated a significant association between circulating AGEs and their soluble receptor levels and both all-cause and cardiovascular mortality (19).…”

Section: Role Of Gut Microbiota In the Modulation Of The Health Effec...mentioning

confidence: 99%

Role of gut microbiota in the modulation of the health effects of advanced glycation end‑products (Review)

et al. 2023

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The aim of the present review was to summarize the potential interactive effects between the gut microbiota and advanced glycation end-product (AGE) accumulation and toxicity in the host, and to reveal potential the mediatory effects of the gut microbiota on AGE-related health effects. The existing data demonstrate that dietary AGEs can have a significant impact on the richness and diversity of the gut microbiota, although the particular effect is dependent on the type of species, as well as the exposure dose. In addition, the gut microbiota may metabolize dietary AGEs. It has been also demonstrated that the characteristics of the gut microbiota, including its richness and relative abundance of certain taxa, is tightly associated with AGE accumulation in the host organism. In turn, a bilateral interplay between AGE toxicity and the modulation of the gut microbiota may contribute to pathogenesis of ageing and diabetes-associated diseases. Bacterial endotoxin lipopolysaccharide appears as the molecule that mediates the interactions between the gut microbiota and AGE toxicity, specifically via the modulation of the receptor for AGE signaling. Therefore, it is proposed that the modulation of the gut microbiota using probiotics or other dietary interventions may have a significant impact on AGE-induced glycative stress and systemic inflammation. Contents1. Introduction 2. Bacterial AGE metabolism 3. The impact of dietary AGE exposure on gut microbiota characteristics and host metabolism 4. Involvement of AGE-gut microbiota interplay in disease pathogenesis 5. Effects of gut microbiota modulation on AGE metabolism and toxicity 6. Role of lipopolysaccharide in the interplay between microbiota and AGE toxicity 7. Conclusions and future perspectives

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Section: Role Of Gut Microbiota In the Modulation Of The Health Effec...mentioning

confidence: 99%

Role of gut microbiota in the modulation of the health effects of advanced glycation end‑products (Review)

et al. 2023

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“…High levels of AGEs are implicated in aging and the development or worsening of degenerative diseases including diabetes, atherosclerosis, chronic kidney disease, and Alzheimer’s disease [ 51 ]. The pathological contribution of AGEs to various diseases is under active investigation [ 4 , 52 , 53 ]. In particular, the accumulation of AGEs was found to contribute to sterility via damage to ovarian cells [ 31 ].…”

Section: Discussionmentioning

confidence: 99%

“…RPL occurs in 1–5% of reproductive-aged women worldwide, but its exact cause is unknown in approximately half of cases [ 2 , 3 ]. While possible causes are suggested, RPL has been understudied, with multiple factors potentially involved, such as genetic factors, environmental factors and certain organic diseases [ 4 ]. Gestational diabetes, which is a common complication of pregnancy, is one factor that increases the risk of spontaneous abortion.…”

Section: Introductionmentioning

confidence: 99%

“…In addition, high blood sugar contributes to the formation of advanced glycation end-products (AGEs), which are toxic metabolic products of lipids, nucleic acids, and proteins formed by non-enzymatic reactions with sugars [ 9 ]. Elevated levels of AGEs are associated with severe health issues such as cancer and vascular diseases and may also play a role in infertility [ 4 ].…”

Section: Introductionmentioning

confidence: 99%

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Genetic Polymorphisms in the 3′-Untranslated Regions of SMAD5, FN3KRP, and RUNX-1 Are Associated with Recurrent Pregnancy Loss

et al. 2022

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Recurrent pregnancy loss (RPL) is typically defined as two or more consecutive pregnancy losses prior to 20 weeks of gestation. Although the causes of idiopathic RPL are not completely understood, vascular development and glucose concentration were reported to correlate with the pregnancy loss. The TGF-β signaling pathway which plays a significant role in pregnancy is activated by the interaction between high glucose and SMAD signaling and affects the vascular cells. SMAD5 and RUNX-1 are involved in the TGF-β signaling pathway and contribute to advanced glycation end products (AGEs) production and vascular development. FN3KRP, a newly described gene, is also associated with vascular diseases and suggested to relate to AGEs. Therefore, in the present study, we investigated associations between RPL risk and genetic polymorphisms of SMAD5, FN3KRP, and RUNX-1 in 388 women with RPL and 280 healthy control women of Korean ethnicity. Participants were genotyped using real-time polymerase chain reaction and restriction fragment length polymorphism assay to determine the frequency of SMAD5 rs10515478 C>G, FN3KRP rs1046875 G>A, and RUNX-1 rs15285 G>A polymorphisms. We found that women with RPL had lower likelihoods of the FN3KRP rs1046875 AA genotype (adjusted odds ratio (AOR), 0.553; p = 0.010) and recessive model (AOR, 0.631; p = 0.017). Furthermore, combination analysis showed that SMAD5 rs10515478 C>G and FN3KRP rs1046875 G>A mutant alleles were together associated with reduced RPL risk. These findings suggest that the FN3KRP rs1046875 G>A polymorphism has a significant role on the prevalence of RPL in Korean women. Considering that it is the first study indicating a significant association between FN3KRP and pregnancy disease, RPL, our results suggest the need for further investigation of the role of FN3KRP in pregnancy loss.

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“… 27 A possible mechanism by which hyperglycemia could induce fertility impairment is the advanced glycation end products accumulation. 28 Moreover, the generation of reactive oxygen species secondary to high glucose levels may damage the developing yolk sac, and epigenetic changes possibly affecting embryogenesis have also been suggested. Certainly, the main mechanism underlying the correlation between diabetes and infertility lies in the hyperinsulinemia and IR discussed previously.…”

Section: Hormonal and Molecular Basis Of Dysmetabolic Infertilitymentioning

confidence: 99%

Female infertility in the era of obesity: The clash of two pandemics or inevitable consequence?

Medenica

Spoltore

Ormazábal

et al. 2022

Clinical Endocrinology

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Obesity is an epidemic that has led to a rise in the incidence of many comorbidities: among others, reduced fertility is often under-evaluated in clinical practice. The mechanisms underlying the link between reduced fertility and obesity are numerous, with insulin resistance, hyperglycaemia and the frequent coexistence of polycystic ovary syndrome being the most acknowledged. However, several other factors concur, such as gut microbiome alterations, low-grade chronic inflammation and oxidative stress. Not only do women with obesity take longer to conceive, but in vitro fertilization (IVF) is also less likely to succeed. We herein provide an updated state-of-the-art regarding the molecular bases of what we could define as dysmetabolic infertility, focusing on the clinical aspects, as well as possible treatment.

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The role of advanced glycation end products in human infertility

Cited by 27 publications

References 101 publications

Role of gut microbiota in the modulation of the health effects of advanced glycation end‑products (Review)

Role of gut microbiota in the modulation of the health effects of advanced glycation end‑products (Review)

Genetic Polymorphisms in the 3′-Untranslated Regions of SMAD5, FN3KRP, and RUNX-1 Are Associated with Recurrent Pregnancy Loss

Female infertility in the era of obesity: The clash of two pandemics or inevitable consequence?

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