Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology

Jinno, M.; Takeuchi, Masayoshi; Watanabe, Aiko; Teruya, Koji; Hirohama, J.; Eguchi, N.; Miyazaki, Akio

doi:10.1093/humrep/deq388

Cited by 82 publications

(69 citation statements)

References 31 publications

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“…A recently published study has demonstrated that in ART patients an increased AGE concentration in human follicular fluid is associated with diminished follicle growth, a lower fertilization rate, and delayed embryo development (Jinno et al 2011).…”

Section: Discussionmentioning

confidence: 99%

Accumulation of advanced glycation end products in the rabbit blastocyst under maternal diabetes

Haucke¹,

Simm²,

Henning³

et al. 2014

Reproduction

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Diabetes mellitus (DM) during pregnancy is one of the leading causes of perinatal morbidity and birth defects. The mechanism by which maternal hyperglycemia, the major teratogenic factor, induces embryonic malformations remains unclear. Advanced glycation end products (AGEs) are known to accumulate during the course of DM and contribute to the development of diabetic complications. Employing a diabetic rabbit model, we investigated the influence of maternal hyperglycemia during the preimplantation period on AGE formation (pentosidine, argpyrimidine, and N 3 -carboxymethyllysine (CML)) in the reproductive tract and the embryo itself. As a consequence of type 1 DM, the AGE levels in blood plasma increased up to 50%, correlating closely with an AGE accumulation in the endometrium of diabetic females. Embryos from diabetic mothers had increased protein-bound CML levels and showed enhanced fluorescent signals for AGE-specific fluorescence in the blastocyst cavity fluid (BCF). The quantification of CML by HPLC-mass spectrometry (MS/MS) showed a higher amount of soluble CML in the BCF of blastocysts from diabetic rabbits (0.26G0.05 mmol/l) compared with controls (0.18G0.02 mmol/l). The high amount of AGEs in blastocysts from diabetic mothers correlates positively with an increased AGER (receptor for AGE (RAGE)) mRNA expression. Our study gives alarming insights into the consequences of poorly controlled maternal diabetes for AGE formation in the embryo. Maternal hyperglycemia during the preimplantation period is correlated with an increase in AGE formation in the uterine environment and the embryo itself. This may influence the development of the embryo through increased AGE-mediated cellular stress by RAGEs.

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Section: Discussionmentioning

confidence: 99%

Accumulation of advanced glycation end products in the rabbit blastocyst under maternal diabetes

Haucke¹,

Simm²,

Henning³

et al. 2014

Reproduction

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“…Jinno et al, in a retrospective analysis of women undergoing IVF, have documented that serum and follicular fluid AGE levels negatively correlated with follicular growth, fertilization rates and embryonic development. What's more, lower follicular fluid AGE levels were the most significant predictors of pregnancy outcomes (158). In another study of women undergoing IVF, follicular fluid levels of soluble form of RAGE (sRAGE) significantly correlated with conception rates (159).…”

Section: Nutrition As a Mediator Of Oxidative Stress In Female Reprodmentioning

confidence: 99%

MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women

Diamanti-Kandarakis

Papalou²,

Kandaraki

et al. 2017

European Journal of Endocrinology

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Nutrition can generate oxidative stress and trigger a cascade of molecular events that can disrupt oxidative and hormonal balance. Nutrient ingestion promotes a major inflammatory and oxidative response at the cellular level in the postprandial state, altering the metabolic state of tissues. A domino of unfavorable metabolic changes is orchestrated in the main metabolic organs, including adipose tissue, skeletal muscle, liver and pancreas, where subclinical inflammation, endothelial dysfunction, mitochondrial deregulation and impaired insulin response and secretion take place. Simultaneously, in reproductive tissues, nutrition-induced oxidative stress can potentially violate delicate oxidative balance that is mandatory to secure normal reproductive function. Taken all the above into account, nutrition and its accompanying postprandial oxidative stress, in the unique context of female hormonal background, can potentially compromise normal metabolic and reproductive functions in women and may act as an active mediator of various metabolic and reproductive disorders.

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“…One study [110] demonstrated that higher levels of AGEs in the follicular fluid and the serum negatively correlated with follicular growth and oocyte fertilization, indication diminished fertility. Another study [111] reported a borderline positive correlation between follicular fluid sRAGE and the number of oocytes retrieved following COH for IVF.…”

Section: Controlled Ovarian Hyperstimulation In Obese Women and The Amentioning

confidence: 99%

“…We [112] and others [110,111,113] have studied the role of the AGE-RAGE system in fertility. One study [114] demonstrated that AGE-modified proteins are present on the surface of freshly isolated human granulosa lutein cells collected from women who underwent COH.…”

Section: Controlled Ovarian Hyperstimulation In Obese Women and The Amentioning

confidence: 99%

“…Jinno, et al [110] measured the levels of toxic AGEs in the blood and the follicular fluid of patients who underwent COH for IVF. They demonstrated that the accumulation of toxic AGEs in follicular fluid and serum negatively correlated with follicular growth, oocyte fertilization, and embryonic development.…”

Section: Controlled Ovarian Hyperstimulation In Obese Women and The Amentioning

confidence: 99%

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Could Advanced Glycation End Products Explain the Poor Response to Controlled Ovarian Hyperstimulation in Obese Women?

Zhang¹,

Merhi²

2016

JED

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Advanced glycation end-products accumulation compromises embryonic development and achievement of pregnancy by assisted reproductive technology

Abstract: Serum TAGE and FF Pent accumulations correlated highly with poor follicular and embryonic development and with a lower likelihood of ongoing pregnancy. Serum TAGE predicts poor ART outcomes independent of age and Day-3 FSH.

Cited by 82 publications

References 31 publications

Accumulation of advanced glycation end products in the rabbit blastocyst under maternal diabetes

Accumulation of advanced glycation end products in the rabbit blastocyst under maternal diabetes

MECHANISMS IN ENDOCRINOLOGY: Nutrition as a mediator of oxidative stress in metabolic and reproductive disorders in women

Could Advanced Glycation End Products Explain the Poor Response to Controlled Ovarian Hyperstimulation in Obese Women?

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