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Leydig cell toxicity

Tolga Mercantepe, Deniz Unal, Levent Tümkaya, Zihni Acar Yazici
Cisplatin is an effective antineoplastic drug that is usually used to treat a number of different types of cancer in the clinic. One of the most notable side effects of cisplatin use is infertility. The present study was designed to determine the non-oxidative testicular effects caused by the use of cisplatin in rats. The rats were randomly allocated to the experimental groups. The untreated rats represented the control group (group I) and the treatment groups were as follows: cisplatin alone (group II), cisplatin+amifostine (group III), cisplatin+curcumin (group IV), and cisplatin+caffeic acid phenethyl ester (CAPE; group V)...
April 2018: Experimental and Therapeutic Medicine
Hyun-Kyoung Kim, Raj Kumar Yadav, Kashi Raj Bhattarai, Han-Wool Jung, Hyung-Ryong Kim, Han-Jung Chae
STUDY QUESTION: Is the Transmembrane BAX Inhibitor Motif-6 (TMBIM6) involved in the molecular mechanism by which cisplatin causes reproductive toxicity? SUMMARY ANSWER: TMBIM6 protects against cisplatin-induced testicular toxicity through up-regulation of heme oxygenase-1 (HO-1),-which maintains the levels of steroidogenic enzymes by decreaseing oxidative stress in the endoplasmic reticulum (ER). WHAT IS KNOWN ALREADY: Testosterone production is highly suppressed as a main complication of cisplatin (cis-diamminedichloroplatinum) anticancer therapy...
January 4, 2018: Human Reproduction
Ukpai A Eze, John Huntriss, Michael N Routledge, Yun Yun Gong
Epidemiological studies show that there is global decline in male fertility primarily as a result of poor sperm quality and this is attributed to exposure to endocrine disrupting chemicals (EDCs) in the environment, food and pharmaceutical products, including mycotoxins and pesticides. The Leydig cells in the male testes are responsible for producing androgens, hormones that play major roles in male development and reproductive function. Therefore, any toxin that affects the function and morphology of the Leydig cells may result in sub-fertility or infertility...
January 4, 2018: Toxicology in Vitro: An International Journal Published in Association with BIBRA
Mei Wang, Ping Su
The Fas/FasL signaling pathway is one of the major pathways that regulate apoptosis. Increasing studies have shown that the activation of the Fas/FasL signaling pathway is closely associated with testicular cell apoptosis. However, the mechanism involved is still unclear. We discuss recent findings regarding the molecular mechanisms by which environmental toxicants induce testicular pathology via Fas/FasL signaling. These findings suggest that Fas/FasL signaling is employed to impact the sensitivity (a response to external factors) of germ cells, disrupt steroidogenic hormone and cytokine metabolism mediated by Sertoli cells, and elicit the activation of NFAT (nuclear factor of activated T-cells) in Leydig cell apoptosis...
January 4, 2018: Systems Biology in Reproductive Medicine
Gessica Dutra Gonçalves, Simone Cristine Semprebon, Bruna Isabela Biazi, Mario Sergio Mantovani, Glaura Scantamburlo Alves Fernandes
Leydig cells are the major testosterone-producing cells of the male reproductive system, and damage to these cells can impair fertility of men. Bisphenol A (BPA) is one of the chemicals with the highest volume of production worldwide. The aim of this study was to evaluate the effects of BPA on the growth, viability, and testosterone production of TM3 murine Leydig cells after exposure to BPA for 24 or 48 h. BPA reduced testosterone production, cell viability and cell growth in a concentration-dependent manner...
December 13, 2017: Reproductive Toxicology
Dibyendu Dutta, In Park, Hiwot Guililat, Samuel Sang, Arpita Talapatra, Barkha Singhal, Nathaniel C Mills
OBJECTIVE: Testosterone depletion induces increased germ cell apoptosis in testes. However, limited studies exist on genes that regulate the germ cell apoptosis. Granzymes (GZM) are serine proteases that induce apoptosis in various tissues. Multiple granzymes, including GZMA, GZMB and GZMN, are present in testes. Th us, we investigated which granzyme may be testosterone responsive and possibly may have a role in germ cell apoptosis aft er testosterone depletion. METHODS: Ethylene dimethane sulfonate (EDS), a toxicant that selectively ablates the Leydig cells, was injected into rats to withdraw the testosterone...
October 26, 2017: Endocrine Regulations
Majid Askaripour, Azam Hasanpour, Foruzan Hosseini, Mojgan Moshrefi, Gholamreza Moshtaghi, Mohammad Hasannejad, Soodeh Rajabi, Seyed Noureddin Nematollahi-Mahani
CONTEXT: Rosa damascena L. (Rosaceae) (RD) essential oil and extracts are commonly used as a flavour in herbal medicine which increase libido. Previous studies have shown inhalation of RD flower's oil increases libido and causes protective effects in formaldehyde (FA)-induced testicular damage. OBJECTIVE: The protective effects of aqueous extract of RD on the male reproductive system of mice were examined following FA-induced damage. MATERIALS AND METHODS: Forty-eight adult NMRI male mice were randomly assigned to six groups (n = 8): control (normal saline, 10 mg/kg); RD40 (40 mg/kg, p...
December 2018: Pharmaceutical Biology
O O Ogedengbe, A I Jegede, I O Onanuga, U Offor, A I Peter, E N Akang, E C S Naidu, O O Azu
The effects of Virgin coconut oil as an adjuvant to highly active antiretroviral therapy (HAART) were investigated on the testicular ultrastructure and biochemical markers in rats. Twenty male Sprague-Dawley rats, weighing 153-169 g were divided into four groups and treated as follows: control A (distilled water), B (HAART), C (HAART+Virgin coconut oil 10 ml/kg) and D (Virgin coconut oil [VCO] 10 ml/kg). Testicular segments were evaluated using transmission electron microscopy. Serum was assayed for testosterone, luteinising hormone, follicle stimulating hormone and testicular tissue for malondialdehyde and glutathione...
April 2018: Andrologia
Mariana Tilinca, Adrian Florea
In this study, we aimed to investigate the testicular toxicity of two molecules derived from bee venom (BV): phospholipase A2 (PlA2) and melittin (Mlt). Ultrastructural effects of purified BV PlA2 and Mlt were assessed consecutive to repeated dose (30 days) and acute toxicity studies. For the subchronic treatment, PlA2 and Mlt were injected in daily doses equivalent to those released by a bee sting (105 μg PlA2/kg/day and 350 μg Mlt/kg/day), while in the acute treatment their doses corresponded to those released by 100 bee stings (9...
January 2018: Toxicon: Official Journal of the International Society on Toxinology
Costantine Albany, Lawrence Einhorn, Lawrence Garbo, Thomas Boyd, Neil Josephson, Darren R Feldman
BACKGROUND: Cytotoxic therapy for relapsed and refractory germ cell tumors or metastatic sex cord stromal tumors is rarely effective and is often accompanied by high adverse event rates. Expression of CD30 has been observed in testicular cancers, and patients with CD30-expressing embryonal carcinomas have worse progression-free survival and overall survival than those with CD30-negative tumors. The objective of this study (NCT01461538) was to characterize the antitumor activity of brentuximab vedotin in patients with CD30-expressing nonlymphomatous malignancies...
March 2018: Oncologist
Huajian Tian, Shaomin Chen, Yang Leng, Teng Li, Zengli Li, Hongxia Chen, Qihao Zhang
Toxic effects of maternal exposure to Cadmium (Cd) on Leydig cells of male offspring arises much concern recently, but its toxic effects on the development of Leydig cells and androgen synthesis have not been elucidated. In this study, female rats were exposed to Cd during gestation and lactation, and the development of Leydig cells in the first filial-generation (F1) male rats was investigated. The steroidogenic signaling pathway and biomarkers related to the development of Leydig cells were detected to disclose how maternal Cd-exposure caused reproductive damage...
March 2018: Environmental Toxicology
Evdochia Adoamnei, Jaime Mendiola, Fernando Vela-Soria, Mariana F Fernández, Nicolás Olea, Niels Jørgensen, Shanna H Swan, Alberto M Torres-Cantero
Bisphenol A (BPA) is a pervasive environmental toxicant with known reproductive effects on sperm parameters and hormone levels. Several observational studies have investigated the associations between BPA exposure and male reproductive function, but findings are inconsistent. The objective of this study was to assess the associations between urinary BPA concentrations and semen quality and reproductive hormone levels in a cross-sectional study with 215 healthy young university students (18-23 years old), investigated between 2010 and 2011 in Southern Spain (Murcia Region)...
November 17, 2017: Environmental Research
Qianying Liu, Zhixin Lei, Menghong Dai, Xu Wang, Zonghui Yuan
Mequindox (MEQ) is a relatively new synthetic antibacterial agent widely applied in China since the 1980s. However, its reproductive toxicity has not been adequately performed. In the present study, four groups of male Kunming mice (10 mice/group) were fed diets containing MEQ (0, 25, 55 and 110 mg/kg in the diet) for up to 18 months. The results show that M4 could pass through the blood-testis barrier (BTB), and demonstrate that Sertoli cells (SCs) are the main toxic target for MEQ to induce spermatogenesis deficiency...
October 20, 2017: Oncotarget
Gopichand Chinta, Mohane Selvaraj Coumar, Latha Periyasamy
Background: Piperine was widely used in traditional medicine for inducing sterility and abortion. Objective: To evaluate the effect of the piperine on testis of male albino rats. Materials and Methods: Adult male rats were divided into four groups ( n = 12). Group I (control): Rats were given vehicle p.o. i.e. 0.5% carboxymethyl cellulose in normal saline daily for 60 days, Group II (ED): Rats received piperine at a dose of 10 mg/kg body weight (b...
October 2017: Pharmacognosy Magazine
Maurya Khushboo, Meesala Krishna Murthy, Maibam Sunita Devi, Sanasam Sanjeev, Kalibulla Syed Ibrahim, Nachimuthu Senthil Kumar, Vikas Kumar Roy, Guruswami Gurusubramanian
Copper is a persistent toxic and bio-accumulative heavy metal of global concern. Continuous exposure of copper compounds of different origin is the most common form of copper poisoning and in turn adversely altering testis morphology and function and affecting sperm quality. L-carnitine has a vital role in the spermatogenesis, physiology of sperm, sperm production and quality. This study was designed to examine whether the detrimental effects of long-term copper consumption on sperm quality and testis function of Wistar albino rat could be prevented by L-carnitine therapy...
November 4, 2017: Environmental Science and Pollution Research International
Xiaolong Wu, Jianpeng Liu, Yue Duan, Shiyu Gao, Yao Lü, Xiaoheng Li, Qiqi Zhu, Xianwu Chen, Jing Lin, Leping Ye, Ren-Shan Ge
Background: Tributyltin (TBT) is widely used as an antifouling agent that may cause reproductive toxicity. The mechanism of TBT on Leydig cell development is still unknown. The objective of the present study was to investigate whether a brief exposure to low doses of TBT permanently affects Leydig cell development and to clarify the underlying mechanism. Methods: Adult male Sprague Dawley rats were randomly assigned into four groups and gavaged normal saline (control), 0.1, 1.0, or 10.0 mg/kg/day TBT for a consecutive 10 days, respectively...
2017: Frontiers in Pharmacology
Luona Wen, Xinwei Jiang, Jianxia Sun, Xia Li, Xusheng Li, Lingmin Tian, Ye Li, Weibin Bai
Cyanidin-3-O-glucoside (C3G) is an anthocyanin that has been reported to reduce the toxicity of heavy metals. In the present study, the protection effects of C3G on the biosynthesis of progesterone, the precursor of testosterone, against lead (Pb) in R2C rat Leydig cells were examined. Treatment of R2C cells with 100 μM Pb resulted in a significant decrease in progesterone production. After being cultured in a medium containing C3G and Pb, R2C cells exhibited an increase in progesterone concentration compared with the Pb treatment, as a result of up-regulation of the expression of the steroidogenic enzymes steroidogenic acute regulatory protein (StAR), 3β-hydroxysteroid dehydrogenase (3β-HSD) and cytochrome P450 enzyme cholesterol side chain cleavage enzyme (CYP11A1)...
October 10, 2017: Food and Chemical Toxicology
Lei Yin, Hongye Wei, Shenxuan Liang, Xiaozhong Yu
Primary testicular cell coculture model has been used to evaluate testicular abnormalities during development, and was able to identify the testicular toxicity of phthalates. However, the primary testicular cell coculture model has disadvantages in employing animals for the isolation of testicular cells, and the complicated isolation procedure leads to inconsistent results. We developed an invitro testicular coculture model from rodent testicular cell lines, including spermatogonial cells, Sertoli cells, and Leydig cells with specified cell density and extracellular matrix (ECM) composition...
October 1, 2017: Toxicological Sciences: An Official Journal of the Society of Toxicology
Raquel Frenedoso da Silva, Cibele Dos Santos Borges, Celina de Almeida Lamas, Valéria Helena Alves Cagnon, Wilma de Grava Kempinas
The acute promyelocytic leukemia (APL) is a rare disease, affecting 0.1/100,000 individuals globally. Despite significant advances in APL therapy, some patients still experience relapsed disease. Currently, arsenic trioxide (As2 O3 ) was found to be effective in relapsed APL treatment and considered as standard treatment for these cases. However, it has been shown that exposure to As2 O3 may exert adverse effects on the male reproductive system since this substance might also induce apoptosis of other important cell types including stem cells...
2017: Journal of Toxicology and Environmental Health. Part A
Jianhai Zhang, Yuchen Zhu, Yan Shi, Yongli Han, Chen Liang, Zhiyuan Feng, Heping Zheng, Michelle Eng, Jundong Wang
Fluoride is known to impair testicular function and decrease testosterone levels, yet the underlying mechanisms remain inconclusive. The objective of this study is to investigate the roles of autophagy in fluoride-induced male reproductive toxicity using both in vivo and in vitro Leydig cell models. Using transmission electron microscopy and monodansylcadaverine staining, we observed increasing numbers of autophagosomes in testicular tissue, especially in Leydig cells of fluoride-exposed mice. Further study revealed that fluoride increased the levels of mRNA and protein expression of autophagy markers LC3, Beclin1, and Atg 5 in primary Leydig cells...
October 11, 2017: Journal of Agricultural and Food Chemistry
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