Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression

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Abstract

Antioxidants have valuable effects on the process of spermatogenesis, particularly with diabetes mellitus (DM). Therefore, the present study investigated the impact and the intracellular mechanisms by which thymoquinone (TQ) works against diabetes-induced testicular deteriorations in rats. Wistar male rats ( n = 60) were randomly allocated into four groups; Control, Diabetic (streptozotocin (STZ)-treated rats where diabetes was induced by intraperitoneal injection of STZ, 65 mg/kg), Diabetic + TQ (diabetic rats treated with TQ (50 mg/kg) orally once daily), and TQ (non-diabetic rats treated with TQ) for 12 weeks. Results revealed that TQ significantly improved the sperm parameters with a reduction in nitric oxide (NO) and malondialdehyde (MDA) levels in testicular tissue. Also, it increased testicular reduced glutathione (GSH) levels and superoxide dismutase (SOD) activity. Interestingly, TQ induced downregulation of testicular inducible nitric oxide synthase (iNOS) and nuclear factor kappa-B (NF-κB) and significantly upregulated the aromatase protein expression levels in testicles in comparison with the diabetic rats. In conclusion, TQ treatment exerted a protective effect against reproductive dysfunction induced by diabetes not only through its powerful antioxidant and hypoglycemic effects but also through its downregulation of testicular iNOS and NF-κB along with upregulation of aromatase expression levels in diabetic rats.

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Testicular Biopsy Score Count – A Method for Registration of Spermatogenesis in Human Testes: Normal Values and Results in 335 Hypogonadal Males

Svend Johnsen (1970)

The paper describes a new and rapid method forregistration of spermatogenesis in human testes: the testicular biopsy score count. Each tubular section is given a score from 10 to 1 according to presence or absence of the main cell types arranged in the order of maturity. Presence of spermatozoa scores 10, 9 or 8; spermatids (and no further) 7 or 6; spermatocytes (and no further) 5 or 4; only spermatogonia 3, only Sertoli cells 2 and no cells 1. The theoretical background of the score count method is discussed and it is emphasized that tissue heterogeneity, being a main point in most conditions, is exposed and evaluated by the method. Normal values are given and results obtained in 335 cases including a great variety of forms of male hypogonadism are presented. Patognomonic score counts leading to immediate diagnosis at a glance are obtained in many instances. A high correlation between testicular biopsy score count and sperm count is found and it is concluded that by this method it has for the first time become possible in man to correlate endocrine conditions with the functional state of the testicular tissue.

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Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species.

João Ramalho-Santos, Sandra Amaral Rocco, Paulo J. Oliveira (2008)

Diabetes Mellitus (DM), a state of chronic hyperglycemia, is a major cause of serious micro and macrovascular diseases, affecting, therefore, nearly every system in the body. Growing evidence indicates that oxidative stress is increased in diabetes due to overproduction of reactive oxygen species (ROS) and decreased efficiency of antioxidant defences, a process that starts very early and worsens over the course of the disease. During the development of diabetes, oxidation of lipids, proteins and DNA increase with time. Mitochondrial DNA mutations have also been reported in diabetic tissues, suggesting oxidative stress-related mitochondrial damage. Diabetes-related oxidative stress may also be the trigger for many alterations on sexual function, which can also include decreased testicular mitochondrial function. Although sexual disorders have been extensively studied in diabetic men, possible changes in the sexual function of diabetic women have only recently received attention. The prevalence of sexual dysfunction in diabetic men approaches 50%, whereas in diabetic women it seems to be slightly lower. Testicular dysfunction, impotence, decreased fertility potential and retrograde ejaculations are conditions that have been described in diabetic males. Diabetes is also the most common cause of erectile dysfunction in men. Poor semen quality has also been reported in diabetic men, including decreased sperm motility and concentration, abnormal morphology and increased seminal plasma abnormalities. In addition, diabetic men may have decreased serum testosterone due to impaired Leydig cell function. Among diabetic women neuropathy, vascular impairment and psychological complaints have been implicated in the pathogenesis of decreased libido, low arousability, decreased vaginal lubrication, orgasmic dysfunction, and dyspareunia. An association between the production of excess radical oxygen species and disturbed embryogenesis in diabetic pregnancies has also been suggested. In fact, maternal diabetes during pregnancy is associated with an increased risk of complications in the offspring, such as altered fetal growth, polyhydramnios, fetal loss and congenital malformations. In addition, hypocalemia and reduced bone mineral content are found in neonates of diabetic mothers. Abnormalities in gametogenesis and sexual function have also been documented in animal models for both types of Diabetes, which thus constitute an important research tool to both study the effects of the disease, and to test novel therapeutical interventions. Because sexuality and fertility are important aspects in the lives of individuals and couples, and considering that over 124 million individuals worldwide suffer from Diabetes, this review highlights the impact of Diabetes and associated oxidative stress on sexual function.

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Estrogen and spermatogenesis.

David Simpson, Jeffrey B. Jones, Eric K Robertson … (2001)

Although it has been known for many years that estrogen administration has deleterious effects on male fertility, data from transgenic mice deficient in estrogen receptors or aromatase point to an essential physiological role for estrogen in male fertility. This review summarizes the current knowledge on the localization of estrogen receptors and aromatase in the testis in an effort to understand the likely sites of estrogen action. The review also discusses the many studies that have used models employing the administration of estrogenic substances to show that male fertility is responsive to estrogen, thus providing a mechanism by which inappropriate exposure to estrogenic substances may cause adverse effects on spermatogenesis and male fertility. The reproductive phenotypes of mice deficient in estrogen receptors alpha and/or beta and aromatase are also compared to evaluate the physiological role of estrogen in male fertility. The review focuses on the effects of estrogen administration or deprivation, primarily in rodents, on the hypothalamo-pituitary-testis axis, testicular function (including Leydig cell, Sertoli cell, and germ cell development and function), and in the development and function of the efferent ductules and epididymis. The requirement for estrogen in normal male sexual behavior is also reviewed, along with the somewhat limited data on the fertility of men who lack either the capacity to produce or respond to estrogen. This review highlights the ability of exogenous estrogen exposure to perturb spermatogenesis and male fertility, as well as the emerging physiological role of estrogens in male fertility, suggesting that, in this local context, estrogenic substances should also be considered "male hormones."

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Author and article information

Contributors

Maurizio Battino: Role: Academic Editor

Francesca Giampieri: Role: Academic Editor

Journal

Journal ID (nlm-ta): Int J Mol Sci

Journal ID (iso-abbrev): Int J Mol Sci

Journal ID (publisher-id): ijms

Title: International Journal of Molecular Sciences

Publisher: MDPI

ISSN (Electronic): 1422-0067

Publication date (Electronic): 27 April 2017

Publication date Collection: May 2017

Volume: 18

Issue: 5

Electronic Location Identifier: 919

Affiliations

[1 ]Department of Physiology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt; mostafa.ataa@ 123456vet.kfs.edu.eg

[2 ]Department of Theriogenology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt; essam.mostafa@ 123456vet.kfs.edu.eg

[3 ]Department of Biochemistry, Faculty of Veterinary Medicine, Damanhour University, Damanhour 22511, Egypt; ali.elfar@ 123456damanhour.edu.eg

[4 ]Department of Animal Physiology, Faculty of Veterinary Medicine, Mansoura University, Mansoura 35516, Egypt; rasha_physiology@ 123456yahoo.com

[5 ]Department of Clinical Pathology, Faculty of Veterinary Medicine, Kafrelsheikh University, Kafrelsheikh 33516, Egypt; doaa.abdelhady1@ 123456vet.kfs.edu.eg

[6 ]Hematology/Pediatric Oncology, King Abdulaziz University Hospital and Scientific Chair of Yousef Abdullatif Jameel of Prophetic Medicine Application, Faculty of Medicine, King Abdulaziz University, Jeddah 21589, Saudi Arabia; saljaouni@ 123456kau.edu.sa

[7 ]Pharmaceutical Research Institute, Albany College of Pharmacy and Health Sciences, Rensselaer, NY 12144, USA

Author notes

[* ]Correspondence: shaker.mousa@ 123456acphs.edu ; Tel.: +1-518-694-7397; Fax: +1-518-694-7567

Article

Publisher ID: ijms-18-00919

DOI: 10.3390/ijms18050919

PMC ID: 5454832

PubMed ID: 28448463

SO-VID: 42b60c6d-4efa-4017-8683-e700f0b1ade9

License:

Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license ( http://creativecommons.org/licenses/by/4.0/).

History

Date received : 09 March 2017

Date accepted : 21 April 2017

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Thymoquinone Defeats Diabetes-Induced Testicular Damage in Rats Targeting Antioxidant, Inflammatory and Aromatase Expression

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Most cited references 52

Testicular Biopsy Score Count – A Method for Registration of Spermatogenesis in Human Testes: Normal Values and Results in 335 Hypogonadal Males

Diabetes and the impairment of reproductive function: possible role of mitochondria and reactive oxygen species.

Estrogen and spermatogenesis.

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Cited by 31

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