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Advanced Glycation End-Products of Follicular Fluid are Associated with Embryo Morphokinetic Parameters and ART Outcomes

  • Reproductive Biology: Original Article
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Abstract

Advanced glycation end products (AGEs) can disrupt antioxidant system and steroidogenesis, resulting in detrimental effects on assisted reproductive technology (ART) outcomes. This study aimed to investigate the association of AGEs in follicular fluid (FF) with morphokinetic parameters of embryos and ART outcomes. Fifty women undergoing ART treatment were studied. AGEs, glucose, 25(OH) vitamin D, malondialdehyde (MDA) levels and catalase (CAT), superoxide dismutase (SOD), and glutathione peroxidase (GPX) activities were evaluated in FF. The expression of 3βHSD, CYP11A1, and CYP19A1 genes were analyzed in granulosa cells (GCs) by qRT-PCR technique. Morphokinetic parameters were evaluated using time-lapse technology. The FF level of AGEs was reversely associated with CAT, SOD, and GPX activities, and total and mature oocytes number, blastocyst formation rate, and high-grade embryos number, while it showed positive correlations with the FF MDA levels, the expression of steroidogenesis genes, number of immature oocytes, morphokinetic parameters, and number of low-grade embryos. Furthermore, the level of vitamin D in FF had an inverse association with AGEs and positive correlations with ART outcomes and morphokinetic parameters. Comparison between the those with positive and negative biochemical pregnancy showed no significant differences in terms of FF factors and just the expression of 3βHSD, CYP11A1, and CYP19A1 genes were higher in pregnant women (p < 0.05). AGEs could delay blastomere division and lead to an increase in the number of low-quality embryos, while vitamin D have an adverse effect on AGEs and a protective function against AGEs negative effects.

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Data Availability

The datasets used and analyzed during the study are available from the corresponding authors on reasonable request.

Abbreviations

AGEs:

Advanced glycation end products

AMH:

Anti-Mullerian hormone

ART:

Assisted reproductive technology

β-hCG:

Beta- human chorionic gonadotropin

CAT:

Catalase

CML:

N-carboxymethyl-lysine

ET:

Embryo transfer

FBS:

Fasting blood glucose

FF:

Follicular fluid

FSH:

Follicle-stimulating hormone

GCs:

Granulosa cells

GPX:

Glutathione peroxidase

ICSI:

Intracytoplasmic sperm injection

LH:

Luteinizing hormone

MDA:

Malondialdehyde

MG-H1:

Methylglyoxal 5-hydro-5-methylimidazolones

PRL:

Prolactin

RAGE:

Receptor for advanced glycation end products

sRAGE:

Soluble receptor for AGE

SOD:

Superoxide dismutase

TAGE:

Toxic AGE

TSH:

Thyroid-stimulating hormone

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Acknowledgements

This study has been extracted from the thesis of Fatemeh Roushenas, registered at the Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences (Thesis No. 67176, IR.TBZMED.REC.1401.230).

Funding

This work was supported by Tabriz University of Medical Sciences [grant numbers: 167176].

Author information

Authors and Affiliations

  1. Department of Reproductive Biology, Faculty of Advanced Medical Sciences, Tabriz University of Medical Sciences, Tabriz, Iran

    Fatemeh Roushenas, Maryam Pashaiasl & Amir Fattahi

  2. Department of Animal Biotechnology, Reproductive Biomedicine Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

    Fatemeh Roushenas, Farnoosh Jafarpour & Mohammad Hossein Nasr-Esfahani

  3. Department of Cellular Biotechnology, Cell Science Research Center, Royan Institute for Biotechnology, ACECR, Isfahan, Iran

    Tayebeh Izadi

  4. Women’s Reproductive Health Research Center, Tabriz University of Medical Sciences, Tabriz, Iran

    Kobra Hamdi

  5. Pooyesh Fertility Center, Isfahan, Iran

    Mohammad Hossein Nasr-Esfahani

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  1. Fatemeh Roushenas
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Contributions

Conceptualization: M.P., A.F., and M.H.N.; Formal analysis: F.R., T.I., and F.J. Investigation: F.R., T.I., and F.J.; Writing—original draft: F.R., K.H. and F.J., Writing—review and editing: A.F., M.H.N., K.H., and M.P.; Project administration and critical revision for important intellectual content: M. P, A.F., and M.H.N.

Corresponding authors

Correspondence to Maryam Pashaiasl, Amir Fattahi or Mohammad Hossein Nasr-Esfahani.

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Ethics Approval

This study was conducted in accordance with the guidelines of the Declaration of Helsinki and was approved by the Ethics Committee of Tabriz University of Medical Sciences (code IR.TBZMED.REC.1401.230).

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The written informed consent was obtained from all patients after providing a detailed explanation of the study.

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Roushenas, F., Izadi, T., Jafarpour, F. et al. Advanced Glycation End-Products of Follicular Fluid are Associated with Embryo Morphokinetic Parameters and ART Outcomes. Reprod. Sci. (2024). https://doi.org/10.1007/s43032-024-01552-5

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