scholarly journals Di-(2 ethylhexyl) phthalate and flutamide alter gene expression in the testis of immature male rats

2009 ◽  
Vol 7 (1) ◽  
pp. 104 ◽  
Author(s):  
Thuy TB Vo ◽  
Eui-Man Jung ◽  
Vu Dang ◽  
Yeong-Min Yoo ◽  
Kyung-Chul Choi ◽  
...  
2009 ◽  
Vol 21 (1) ◽  
pp. 211
Author(s):  
K.-C. Choi ◽  
T. T. B. Vo ◽  
E.-M. Jung ◽  
V. H. Dang ◽  
E.-B. Jeung

In a previous study, we demonstrated that although endocrine disruptors (EDs) with androgenic and anti-androgenic effects may alter reproductive function, their effects on the developing male reproductive organs may be distinct. To continue this line of study, we treated immature rats to examine the adverse effects of di-(2 ethylhexyl) phthalate (DEHP) and flutamide (Flu) on the male reproductive system. Immature male SD rats were treated daily with DEHP and/or Flu at postnatal day (PND) 21 to 35 in a dose-dependent manner, and the changes evoked by these EDs were determined by differences in male reproductive tract and other organ weights, testicular histology, and serum LH and testosterone levels in combination with global microarray analysis. Interestingly, the testes, prostate, seminal vesicle weight, and anogenital distances were significantly decreased in response to the highest dose of DEHP and Flu. There were no differences in serum LH and testosterone concentration at PND 35 for immature male rats exposed to DEHP and/or Flu. However, treatment with DEHP and/or Flu caused histopathological changes in testes in which the degeneration and denseness of germ cells and/or dilatation of the tubular lumen were observed in response to the high dose [500 mg kg–1 of body weight (BW)] of DEHP and medium dose (10 mg kg–1 of BW) of Flu. Additionally, the results from cDNA microarray indicated that 1272 genes were up-regulated (more than 2-fold) and 1969 genes were down-regulated in response to DEPH and/or Flu. These genes were identified based on their roles in some physiological processes (i.e. lipid and cholesterol homeostasis, steroidogenesis, sex determination, and calcium signal transduction). The significant decreases were observed in the expressions of steroidogenic genes (i.e. Star, Cyp11a1, or Hsd3b). In addition, a common set of targeting genes, including CaBP1, Vav2, Plcd1, Lhx1, and Isoc1, were altered following EDs exposure, suggesting a potential set of biomarker genes for screening anti-androgenic and/or androgenicity of EDs. Taken together, we demonstrated that exposure to DEHP and/or Flu resulted in a temporal alteration in gene expression profile in the testes of immature male rats, and their toxicological effects on male reproductive system are distinct depending on their anti-androgenicity, suggesting new insight into molecular mechanism(s) underlying detrimental impacts of EDs with anti-androgenic activities in human and wildlife.


2009 ◽  
Vol 57 (4) ◽  
pp. 777-784 ◽  
Author(s):  
Giuliana G. K. Botelho ◽  
Munisa Golin ◽  
Aedra C. Bufalo ◽  
Rosana N. Morais ◽  
Paulo R. Dalsenter ◽  
...  

2018 ◽  
Vol 7 (3) ◽  
pp. 408-414 ◽  
Author(s):  
Xiaoyun Qin ◽  
Quan Ma ◽  
Jianhui Yuan ◽  
Xinnan Hu ◽  
Qin Tan ◽  
...  

The objective of this study is to determine testicular pathological damage and explore its molecular mechanisms after di-2-ethylhexyl phthalate (DEHP) treatment.


2020 ◽  
Vol 21 (1) ◽  
pp. 31-35
Author(s):  
Basma El-Desoky ◽  
Shaimaa El-Sayed ◽  
El-Said El-Said

Objective: Investigating the effect of green tea extract (GTE) on the testicular damage induced by cadmium chloride CdCl2 in male rats. Design: Randomized controlled study. Animals: 40 male Wistar rats. Procedures: Rats were randomly divided into four groups: A) control group (each rat daily received pellet diet); B) GTE group each rat daily received pellet diet as well as 3 ml of 1.5 % w/v GTE, C) CdCl2 group each rat was I/P injected a single dose of 1 mg/kg CdCl2, then daily received pellet diet, and D) CdCl2+GTE group each rat was I/P injected a single dose of 1 mg/kg CdCl2 then daily received pellet diet as well as 3 ml of 1.5 % w/v GTE. After 30 days, blood samples were collected for hormonal assays (testosterone, FSH, and LH). In addition, both testes were collected; one of them was used for quantification of 17-beta hydroxysteroid dehydrogenase III (17β-HSDIII) gene expression using a real-time PCR. The other testis was used for determination of catalase and reduced glutathione; GSH, Nitric oxide (NO) and malondialdehyde (MDA) levels. Results: CdCl2 decreased serum testosterone levels and its synthesis pathway (17β-HSDIII testicular gene expression). While antioxidants catalase and GSH were reduced, oxidants MDA were enriched in the testes of CdCl2-poisoned rats. This CdCl2-promoted testicular dysfunction was corrected via the administration of GTE to male rats. Conclusion and clinical relevance: GTE could be used as a remedy for protecting against CdCl2-induced testicular damage in male rats.


2020 ◽  
Vol 26 ◽  
Author(s):  
Abdulqader Fadhil Abed ◽  
Yazun Bashir Jarrar ◽  
Hamzeh J Al-Ameer ◽  
Wajdy Al-Awaida ◽  
Su-Jun Lee

Background: Oxandrolone is a synthetic testosterone analogue that is widely used among bodybuilders and athletes. However, oxandrolone causes male infertility. Recently, it was found that metformin reduces the risk of infertility associated with diabetes mellitus. Aim: This study aimed to investigate the protective effects of metformin against oxandrolone-induced infertility in male rats. Methods: Rats continuously received one of four treatments (n=7) over 14 days: control DMSO administration, oxandrolone administration, metformin administration, or co-administration of oxandrolone and metformin. Doses were equivalent to those used for human treatment. Subsequently, testicular and blood samples were collected for morphological, biochemical, and histological examination. In addition, gene expression of the testosterone synthesizing enzyme CYP11A1 was analyzed in the testes using RT-PCR. Results: Oxandrolone administration induced male infertility by significantly reducing relative weights of testes by 48%, sperm count by 82%, and serum testosterone levels by 96% (ANOVA, P value < 0.05). In addition, histological examination determined that oxandrolone caused spermatogenic arrest which was associated with 2-fold downregulation of testicular CYP11A1 gene expression. However, co-administration of metformin with oxandrolone significantly ameliorated toxicological alterations induced by oxandrolone exposure (ANOVA, P value < 0.05). Conclusion: Metformin administration protected against oxandrolone-induced infertility in male rats. Further clinical studies are needed to confirm the protective effect of metformin against oxandrolone-induced infertility among athletes.


2021 ◽  
pp. 107479
Author(s):  
Xiaofan Xiong ◽  
Lin Han ◽  
Meiyang Fan ◽  
Lingyu Zhang ◽  
Liying Liu ◽  
...  

2021 ◽  
Vol 22 (12) ◽  
pp. 6197
Author(s):  
Paola Brivio ◽  
Giulia Sbrini ◽  
Letizia Tarantini ◽  
Chiara Parravicini ◽  
Piotr Gruca ◽  
...  

Epigenetics is one of the mechanisms by which environmental factors can alter brain function and may contribute to central nervous system disorders. Alterations of DNA methylation and miRNA expression can induce long-lasting changes in neurobiological processes. Hence, we investigated the effect of chronic stress, by employing the chronic mild stress (CMS) and the chronic restraint stress protocol, in adult male rats, on the glucocorticoid receptor (GR) function. We focused on DNA methylation specifically in the proximity of the glucocorticoid responsive element (GRE) of the GR responsive genes Gadd45β, Sgk1, and Gilz and on selected miRNA targeting these genes. Moreover, we assessed the role of the antipsychotic lurasidone in modulating these alterations. Chronic stress downregulated Gadd45β and Gilz gene expression and lurasidone normalized the Gadd45β modification. At the epigenetic level, CMS induced hypermethylation of the GRE of Gadd45β gene, an effect prevented by lurasidone treatment. These stress-induced alterations were still present even after a period of rest from stress, indicating the enduring nature of such changes. However, the contribution of miRNA to the alterations in gene expression was moderate in our experimental conditions. Our results demonstrated that chronic stress mainly affects Gadd45β expression and methylation, effects that are prolonged over time, suggesting that stress leads to changes in DNA methylation that last also after the cessation of stress procedure, and that lurasidone is a modifier of such mechanisms.


1933 ◽  
Vol 58 (5) ◽  
pp. 569-574 ◽  
Author(s):  
Herbert M. Evans ◽  
Edwin L. Gustus ◽  
Miriam E. Simpson

The gonadotropic hormone of the blood of the pregnant mare has been greatly concentrated by adsorption on active aluminum hydroxide followed by elution. The preparations so obtained gave demonstrable gonadotropic effects within 100 hours in 21 day old female mice following three subcutaneous injections of 0.001 mg. in 1 cc. of physiological saline. As is well known, other gonadotropic substances do not cause conspicuous development of the male gonads but injections of comparatively large doses of these preparations into immature male rats caused marked development of the testes, which in 10 days were trebled in weight. An astonishing increase in the weight of the seminal vesicles resulted, for these organs were approximately 75 times heavier than in controls.


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