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Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management

Abstract

Infertility is a global health problem involving about 15% of couples. Approximately half of the infertility cases are related to male factors. The oxidative stress, which refers to an imbalance in levels of reactive oxygen species (ROS) and antioxidants, is one of the main causes of infertility in men. A small amount of ROS is necessary for the physiological function of sperm including the capacitation, hyperactivation and acrosomal reaction. However, high levels of ROS can cause infertility through not only by lipid peroxidation or DNA damage but inactivation of enzymes and oxidation of proteins in spermatozoa. Oxidative stress (OS) is mainly caused by factors associated with lifestyle. Besides, immature spermatozoa, inflammatory factors, genetic mutations and altering levels of sex hormones are other main source of ROS. Since OS occurs due to the lack of antioxidants and its side effects in semen, lifestyle changes and antioxidant regimens can be helpful therapeutic approaches to overcome this problem. The present study aimed to describe physiological ROS production, roles of genetic and epigenetic factors on the OS and male infertility with various mechanisms such as lipid peroxidation, DNA damage, and disorder of male hormone profile, inflammation, and varicocele. Finally, the roles of oral antioxidants and herbs were explained in coping with OS in male infertility.

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Abbreviations

·OH:

Hydroxyl

·ROO:

Proxyl

4-HNE:

4-Hydroxynonenal

8-OHdG:

8-Hydroxy-2-deoxyguanosine

ABP:

Androgen-binding protein

ARE:

Antioxidant responsive element

ARTs:

Assisted reproductive techniques

ATP:

Adenosine triphosphate

BER:

Base excision repair

cAMP:

Cyclic adenosine monophosphate

CAT:

Catalase

CK:

Creatine kinase

CYP2E:

Cytochrome P450 enzymes

ETC:

Electron transport chain

G6PD:

Glucose-6-phosphate dehydrogenase

GnRH:

Gonadotropin releasing hormone

GPx:

Glutathione peroxidase

GRX:

Glutaredoxin

GSH:

Glutathione

GST:

Glutathione s-transferase

H2O2 :

Hydrogen peroxide

HPA:

Hypothalamic–pituitary–adrenal

HPG:

Hypothalamic–pituitary–gonadal

HPT:

Hypothalamo–pituitary–thyroid

IL:

Interleukin

LOOHs:

Lipid hydroperoxides

MDA:

Malondialdehyde

miRNAs:

Micro-ribonucleic acids

MPO:

Myeloperoxidase

NAC:

N-Acetylcysteine

NADPH:

Adenine dinucleotide phosphate

NO:

Nitrogen oxide

NOS:

Nitric oxide synthase

NRF2:

Nuclear factor erythroid 2-related factor 2

O ·−2 :

Superoxide anion

ONOO-:

Peroxynitrite

OS:

Oxidative stress

P-Tyr:

Phosphotyrosine

PGE2:

Prostaglandin E2

PKA:

Protein kinase A

NER:

Nucleotide excision repair

PMN:

Polymorphonuclear

P-PKA:

Phospho-PKA

PRX:

Peroxiredoxin

PUFA:

Polyunsaturated fatty acids

RF:

Radio frequency

ROOH:

Hydroperoxide

ROS:

Reactive oxygen species

SCI:

Spinal cord injury

SDF:

Sperm DNA fragmentation

SH-:

Sulfhydryl groups

SOD:

Superoxide dismutase

SOD3:

Extracellular SOD

TAC:

Total antioxidant capacity

TNF-α:

Tumor necrosis factor alpha

TRX:

Thioredoxin

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Acknowledgements

This work was supported by grants from the Vice Chancellor for Research and Technology, Kashan University of Medical Sciences, Kashan, Iran.

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Barati, E., Nikzad, H. & Karimian, M. Oxidative stress and male infertility: current knowledge of pathophysiology and role of antioxidant therapy in disease management. Cell. Mol. Life Sci. 77, 93–113 (2020). https://doi.org/10.1007/s00018-019-03253-8

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Keywords

  • Male infertility
  • Oxidative stress
  • Reactive oxygen species
  • Genetic factors
  • Antioxidants