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The effect of streptozotocin induced diabetes on sperm function: a closer look at AGEs, RAGEs, MAPKs and activation of the apoptotic pathway

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Abstract

This study was designed to (1) investigate the possible mechanisms through which diabetes-induced advanced glycation end products (AGEs) and receptor for AGEs (RAGE) activation can affect male reproductive function; and (2) corroborate the interaction of previously established independent pathways. Male albino Wistar rats (14-weeks old) weighing 250–300 g received either a single intraperitoneal injection of streptozotocin (30 mg/kg or 60 mg/kg), represented as STZ30 or STZ60 respectively, or citrate buffer (control). Diabetes mellitus (DM) was confirmed if plasma glucose levels were ≥ 14 mmol/L after 1 week. Animals were sacrificed after 8 weeks of treatment by an overdose of sodium pentobarbital (160 mg/kg body weight). The testes and epididymides were harvested. The testes were used for biochemical and Western blot analysis, while sperm was retrieved from the epididymis and analysed with computer-aided sperm analysis. The blood glucose levels of STZ60 animals were above the cut-off point and hence these animals were regarded as diabetic. Diabetic animals presented with a non-significant increase in AGE and RAGE expression. Diabetic animals showed a significant increase in the expression of cleaved caspase 3 compared to control (p < 0.001), and these animals also presented with an increase in the expression of JNK (p < 0.05), PARP (p = 0.059) and p38 MAPK (p = 0.1). Diabetic animals also displayed decreased catalase activity accompanied by a non-significant increase in malondialdehyde levels. Additionally, there was a significant decrease in the percentage of progressively motile spermatozoa (p < 0.05) in diabetic animals. This study has shed some light on the interplay between DM, AGE, RAGE and mitogen-activated protein kinase signalling in the testes of diabetic rats, which can result in altered sperm function and contribute to male infertility. However, more studies are needed to better understand this complicated process.

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Abbreviations

AGE:

Advanced glycation end product

BCA:

Bicinchoninic acid

CASA:

Computer aided sperm analysis

DM:

Diabetes mellitus

DNA:

Deoxyribonucleic acid

GnRH:

Gonadotropin-releasing hormone

ICAM-1:

Intercellular adhesion molecule-1

JNK:

C-Jun N-terminal kinase

MAPKs:

Mitogen-activated protein kinase

MCP-1:

Monocyte chemoattractant protein-1

MDA:

Malondialdehyde

Nf-kB:

Nuclear factor kappa B

OS:

Oxidative stress

PARP:

Poly adenosine diphosphate-ribose polymerase

PUFA:

Polyunsaturated fatty acid

RAGE:

Receptor for advanced glycation end product

ROS:

Reactive oxygen species

SF:

Supplementary figure

STZ:

Streptozotocin

TBA:

Thiobarbituric acid

VCAM-1:

Vascular cell adhesion molecule-1

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Acknowledgements

The authors would like to thank Dr. Michelle Smit-van Schalkwyk and Dr. Shantal Windvogel for the generous donation of tissue samples and Harry Crossley Foundation for the research grant provided.

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Authors and Affiliations

  1. Division of Medical Physiology, Faculty of Medicine and Health Sciences, Stellenbosch University, Francie van Zijl Drive, Tygerberg, 7505, South Africa

    Temidayo S. Omolaoye & Stefan S. Du Plessis

  2. Department of Basic Sciences, College of Medicine, Mohammed Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates

    Stefan S. Du Plessis

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Correspondence to Stefan S. Du Plessis.

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Omolaoye, T.S., Du Plessis, S.S. The effect of streptozotocin induced diabetes on sperm function: a closer look at AGEs, RAGEs, MAPKs and activation of the apoptotic pathway. Toxicol Res. 37, 35–46 (2021). https://doi.org/10.1007/s43188-020-00040-7

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