In utero exposure to dicyclohexyl and di-n-hexyl phthalate possess genotoxic effects on testicular cells of male rats after birth in the comet and TUNEL assays

2013 ◽  
Vol 33 (3) ◽  
pp. 230-239 ◽  
Author(s):  
M A Ahbab ◽  
Ü Ündeğer ◽  
N Barlas ◽  
N Başaran

Phthalates are diester derivatives of phthalic acid widely used in many commercial applications. The aim of this study is therefore to evaluate possible genotoxicity of di- n-hexyl phthalate (DHP) and dicyclohexyl phthalate (DCHP) at different concentrations using single-cell gel electrophoresis (comet) and terminal deoxynucleotidyl transferase deoxyuridine triphosphate nick end-labeling (TUNEL) assays in testes samples of male rat pups. DCHP and DHP in corn oil were administered to the pregnant rats by gavage at the doses of 0 (vehicle), 20, 100, and 500 mg kg−1 day−1 from gestational day 6 (GD6) to GD19. After delivery, male rats were allowed to grow until prepubertal, pubertal, and adulthood. At necropsy, the blood samples were collected from heart and were excised immediately. The apoptotic cells of prepubertal, pubertal, and adult testis were detected using TUNEL assay. The comet assay was performed on blood lymphocytes and testes samples of adult male rats. The comet assay results showed that tail length, tail intensity, olive tail moment (OTM), and percentage of DNA present in tail were higher when DHP content was increased. Judging from the values of OTM and percentage of DNA, DHP could significantly induce DNA breakage at doses of 100 and 500 mg kg−1 day−1 compared with the control group. An increase in TUNEL-positive cells of prepubertal, pubertal, and adult testicular cells was observed in the treated groups. In conclusion, prenatal exposure to DHP and DCHP may possess genotoxic risk to testicular cells of rats at all stages of development, even at adulthood.

1976 ◽  
Vol 71 (3) ◽  
pp. 289-297 ◽  
Author(s):  
A. S. GOLDMAN ◽  
R. D. EAVEY ◽  
MARY K. BAKER

SUMMARY Two new synthetic steroid analogues, (I) 16β-bromo-3β,17α-dihydroxy-5α-pregnane-11,20-dione and (II) 17β-ureido-1,4-androstadien-3-one have been shown to give kinetic patterns consistent with active-site-directed irreversible inhibition of adult rat testicular microsomal steroid 17α-hydroxylase and C17-20 lyase in vitro. Administration of both analogues to adult male rats for 24 h produced potent inhibition of these testicular enzymes in vivo. Given to pregnant rats during the critical period of male organogenesis they produced hypospadias: a characteristic of the syndrome in man in which these enzymes are defective genetically. Given to male rat pups during the first 9 days of life, inhibitor II produced significantly smaller prostates and seminal vesicles in adulthood, indicating the usefulness of this inhibitor in studies on the role of testosterone in neonatal programming of target organ size in adulthood. Thus, two new enzyme inhibitors have been shown to block testosterone production in the foetal and neonatal rat selectively at the site of the hydroxylase without other apparent hormonal effects or influence on adrenal size.


1970 ◽  
Vol 36 (1) ◽  
pp. 103-109 ◽  
Author(s):  
S Talukder ◽  
MA Hossain ◽  
S Sarker ◽  
MAH Khan

To evaluate the antifertility effect of crude mixture of A. precatorius seeds at the dose level of 50 mg/kg body weight in adult male rats, after oral administration to male rats for 40 days, the rats were sacrificed and hormonal profiles, serum biochemistry, sperm count and histological changes were recorded. A sharp decrease in the serum levels of testosterone (0.70 ± 0.17 ng/ml), FSH (0.70 ± 0.22 lU/L), and LH (0.87 ± 0.35 IU/L) was detected compared to control (FSH, LH and testosterone levels 0.93 ± 0.15 ng/ml, 0.76 ± 0.28 IU/L, 1.44 ± .011 IU/L, respectively). A significant reduction of epididymal sperm count (2.34 million/mL) was noted in treated rats as compared to control group (7.87 million/mL). Histology of testes showed marked atrophy of the testes, which was characterized by disruption of the seminiferous epithelium and atrophy of the Leydig cells. Crude mixture of A. precatorius seed has a negative impact on male reproductive functions. It might be suggested that crude mixture of A. precatorius seeds might have antifertility property for male rats.   Keywords: Abrus precatorius; antifertility; male rat; testosterone. DOI: http://dx.doi.org/10.3329/bjar.v36i1.9234 BJAR 2011; 36(1): 103-109


2019 ◽  
Vol 8 (5) ◽  
pp. 741-753 ◽  
Author(s):  
Israa F. Mosa ◽  
Mokhtar I. Yousef ◽  
Maher Kamel ◽  
Osama F. Mosa ◽  
Yasser Helmy

Abstract Hydroxyapatite nanoparticles (HAP-NPs) are an inorganic component of natural bone and are mainly used in the tissue engineering field due to their bioactivity, osteoconductivity, biocompatibility, non-inflammatory, and non-toxicity properties. However, the current toxicity data for HAP-NPs regarding human health are limited, and only a few results from basic studies have been published. Therefore, the present study was designed to investigate the beneficial role of chitosan nanoparticles (CsNPs) and curcumin nanoparticles (CurNPs) in alleviating nephrotoxicity induced by HAP-NPs in male rats. The results showed that HAP-NPs caused a reduction in antioxidant enzymes and induced lipid peroxidation, nitric oxide production and DNA oxidation. Moreover, HAP-NP administration was associated with intense histologic changes in kidney architecture and immunoreactivity to proliferating cell nuclear antigen (PCNA). However, the presence of CsNPs and/or CurNPs along with HAP-NPs reduced the levels of oxidative stress through improving the activities of antioxidant enzymes. Also, the rats administered the nanoparticles showed a moderate improvement in glomerular damage which matched that of the control group and showed mild positive reactions to PCNA–ir in glomeruli and renal tubules in the cortical and medullary portions. These novel insights confirm that the presence of chitosan and curcumin in nanoforms has powerful biological effects with enhanced bioactivity and bioavailability phenomena compared to their microphase counterparts. Also, they were able to ameliorate the nephrotoxicity induced by HAP-NPs.


2020 ◽  
Vol 36 (7) ◽  
pp. 502-513
Author(s):  
Işil Aydemir ◽  
Caner Özbey ◽  
Oktay Özkan ◽  
Şadiye Kum ◽  
Mehmet İbrahim Tuğlu

Bisphenol-A (BPA) used in the production of plastic materials is a temperature-soluble agent. It also has a steroid hormone-like activity; therefore, it poses a danger to human health. In our study, we aimed to investigate the effects of BPA on lymph node and spleen in male rats exposed to this agent during prenatal stage. The pregnant female rats were divided into four groups: control, sham, low dose (300 µg/kg BPA), and high dose (900 µg/kg BPA). BPA was dissolved in 1 mL of corn oil and administered to the pregnant rats every day during pregnancy. On the 21st and 45th day after the birth, male rats’ lymph node and spleen samples were taken and histopathological examination was performed. Samples were stained with hematoxylin and eosin to determine the general histological appearance, and with CD3 and CD20 immunohistochemically. The results of staining were evaluated by H-score, and statistical analysis was performed. In the samples, BPA applications were not found to cause significant tissue damage. But there was a significant decrease in the immunoreactivities of CD3 and CD20 after BPA applications in both 21st and 45th day samples. After high dose BPA administration, decreased CD3 immunoreactivity was statistically significant. It is thought that BPA does not cause histologically significant tissue damage, but it may impair organ function at cellular level. The investigation of molecules involved in organ function will be useful in revealing the mechanisms that will cause dysfunction.


2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Minji Park ◽  
Yuri Choi ◽  
Hyeonhae Choi ◽  
Ju-Yearn Yim ◽  
Jaesook Roh

Prenatal caffeine exposure adversely affects the development of the reproductive organs of male rat offspring. Thus, it is conceivable that peripubertal caffeine exposure would also influence physiologic gonadal changes and function during this critical period for sexual maturation. This study investigated the impact of high doses of caffeine on the testes of prepubertal male rats. A total of 45 immature male rats were divided randomly into three groups: a control group and 2 groups fed 120 and 180 mg/kg/day of caffeine, respectively, via the stomach for 4 weeks. Caffeine caused a significant decrease in body weight gain, accompanied by proportional decreases in lean body mass and body fat. The caffeine-fed animals had smaller and lighter testes than those of the control that were accompanied by negative influences on the histologic parameters of the testes. In addition, stimulated-testosterone ex vivo production was reduced in Leydig cells retrieved from the caffeine-fed animals. Our results demonstrate that peripubertal caffeine consumption can interfere with the maturation and function of the testis, possibly by interrupting endogenous testosterone secretion and reducing the sensitivity of Leydig cells to gonadotrophic stimulation. In addition, we confirmed that pubertal administration of caffeine reduced testis growth and altered testis histomorphology.


2020 ◽  
Vol 32 (10) ◽  
pp. 914
Author(s):  
M. S. Garcia ◽  
W. A. Orcini ◽  
R. L. Peruquetti ◽  
J. E. Perobelli

This study investigated the reproductive toxicity of methylmercury (MeHg) and Aroclor (Sigma-Aldrich), alone or in combination, following exposure of prepubertal male rats considering the chromatoid body (CB) as a potential target. The CB is an important molecular regulator of mammalian spermatogenesis, primarily during spermatid cytodifferentiation. Male Wistar rats were exposed to MeHg and/or Aroclor , according the following experimental design: control group, which was administered in corn oil (vehicle) only; MeHg-treated group, which was administered 0.5mg kg−1 day−1 MeHg; Aroclor-treated group, which was administered 1mg kg−1 day−1 Aroclor; Mix-LD, group which was administered a low-dose mixture of MeHg (0.05mg kg−1 day−1) and Aroclor (0.1mg kg−1 day−1); and Mix-HD group, which was administered a high-dose mixture of MeHg (0.5mg kg−1 day−1) and Aroclor (1.0mg kg−1 day−1). MeHg was diluted in distilled water and Aroclor was made up in corn oil (volume 1mL kg−1). Rats were administered the different treatments from PND23 to PND53 by gavage, . The morphophysiology of CBs was analysed, together with aspects of steroid hormones status and regulation, just after the last treatment on PND53. In addition, the long-term effects on sperm parameters were assessed in adult animals. MeHg exposure increased mouse VASA homologue (MVH) protein levels in seminiferous tubules, possibly affecting the epigenetic status of germ cells. Aroclor produced morphological changes to CB assembly, which may explain the observed morphological defects to the sperm flagellum and the consequent decrease in sperm motility. There were no clear additive or synergistic effects between MeHg and Aroclor when administered in combination. In conclusion, this study demonstrates that MeHg and Aroclor have independent deleterious effects on the developing testis, causing molecular and morphological changes in CBs. To the best of our knowledge, this is the first study to show that CBs are targets for toxic agents.


2021 ◽  
Vol 9 (B) ◽  
pp. 670-678
Author(s):  
Nurdiana Nurdiana ◽  
Pradnyawati Chania ◽  
Rifzi Nurvitasari ◽  
Azmiatun Nisa ◽  
Styan Wahyu Diana ◽  
...  

AIM: This research aims to examine the effects of soy milk on mounting latency (ML), mounting frequency (MF), estrogen levels, androgen-binding protein (ABP) expression, and spermatogenesis in male rats (Rattus norvegicus). METHODS: Twenty-four male wistar rats (Rattus norvegicus) aged 4 weeks were divided into four groups. Control group (given a normal diet), P1; P2; P3 (given the normal diet and soy milk powder at doses of 7.1; 14.2; 21.3 g/KgBW/day, respectively) for 6 weeks. Observation of ML and MF were performed at 9 weeks 5 days of age, and rat surgery was performed at 10 weeks of age. Analysis of estrogen hormone levels was conducted by enzyme-linked immunosorbent assay (ELISA), ABP staining was using immunohistochemistry method, testicular spermatogenesis was observed using histopathological methods, and observation of spermatozoa was performed under the microscope.  RESULTS: The results showed no significant reduction of ML and MF, estrogen levels, and ABP expression (p ≤ 0.256; 0.865; 0.959, respectively) in male rat, but there was a significant decrease in the number, morphology, motility of spermatozoa, and testicular histophatology, (p ≤ 0.000, 0.003, 0.008, 0.000, respectively). CONCLUSION: The administrassion of soy milk in various doses (7.1;14.2;21.3 g/KgBW/day) in male Wistar rats (Rattus norvegicus) had showed significantly difference on histopathological evaluation using Johnson’s scoring system, sperm quantity and quality, while on mounting latency and frequency, estrogen levels, and ABP expressions did not show significantly difference between groups. That describe of isoflavone in soy milk can affect several aspects related to male endocrine and reproductive development.


2021 ◽  
Vol 53 (2) ◽  
Author(s):  
Amelya Permata Sari ◽  
Cimi Ilmiawati ◽  
Mohamad Reza

High-dose Monosodium Glutamate (MSG) expo sure increases the estrogen level in pregnant rats. However, there are limited data available on whether the MSG-related maternal hormonal effects can affect male litters' genitalia phenotype. This study aimed to analyze the impact of MSG on estrogen level in pregnant rats and anogenital distance in male pups. Experiment for this study was performed at the animal facility of Biomedical Laboratory at the Faculty of Medicine, Universitas Andalas, from April 2019 to February 2020. Pregnant Wistar rats were given MSG orally at 2 and 4 mg/g body weight (BW) for 20 days. On day 21, pregnant rats were sacrificed and blood was drawn intracardially. Estradiol serum level was measured by ELISA. Male pups were counted, and the anogenital distance (AGD) was measured. Maternal serum estradiol levels were statistically analyzed by One-Way ANOVA and the AGD of male litters were analyzed by the Kruskal-Wallis test. Results showed that perinatal MSG exposure increased the estradiol level (26.3±4.5 pg/ml; 37.5±6.7 pg/ml; 62.1±8.2 pg/ml in control, 2 mg/g BW, and 4 mg/g BW group, respectively [mean±SD; p=<0.001]) and decreased the AGD (4 mm; 3 mm; 1.5 mm in control, 2 mg/g BW, and 4 mg/gBW group, respectively [median; p=<0.01]) in a dose-dependent manner. Thus, MSG exposure during pregnancy is a risk factor for male rat feminization.


Author(s):  
Mehmet Erman Erdemli ◽  
Eyüp Altınöz ◽  
Zeynep Aksungur ◽  
Zümrüt Doğan ◽  
Harika Gözükara Bağ ◽  
...  

Investigate the changes that occur in the placenta tissues of pregnant rats that were administered acrylamide (AA) and vitamin E as a protective agent during pregnancy. Thirty rats that were proven positive for pregnancy with vaginal smear test were randomly distributed into control, corn oil, vitamin E, acrylamide and vitamin E + acrylamide groups. Pregnant rats were decapitated on the 20th day of the experiment. Malondialdehyde (MDA), reduced glutathione (GSH), total antioxidant capacity (TAS), total oxidant capacity (TOS) and Xanthine oxidase (XO) levels were measured in placenta tissues. It was determined that acrylamide application during pregnancy statistically significantly increased MDA, TOS and XO levels and reduced GSH and TAS levels in the placenta tissue of pregnant rats when compared to all other groups, and GAS and TAS levels statistically significantly increased in vitamin E administered group when compared to all other groups and TOS and XO levels were decreased to control group levels. It was observed that orally administered AA changed the antioxidant / oxidant equilibrium favoring the oxidants by increasing MDA, XO and TOS levels in pregnant rats and caused oxidative stress, while vitamin E administration returned the antioxidant / oxidant equilibrium back to normal levels, preventing oxidative stress induced toxicity.


2017 ◽  
Vol 3 (6) ◽  
pp. 702 ◽  
Author(s):  
Dwi Gayatri Nurcahyawati ◽  
Hani Plumeriastuti ◽  
Lilik Maslachah

The purpose of this study was to know the effect of Dayak onion tuber extract (Eleutherine palmifolia) given by per oral in lowering levels of histophatology damage kidney of albino male rat (Rattus norvegicus) strain Wistar which was induced by alloxan. Animals which were used in this research were 24 white male rats (Rattus norvegicus) strain Wistar, and then divided into 6 groups. The negative control group K (-) were given with aquabidest and CMC-Na 1% during the therapy period, the positive control group K (+) were given with alloxan 110 mg / kgbw, the group of drug control K (O) were given with alloxan and oral therapy  with metformin 9 mg / 200g bw / day, the treatment group 1 (P1) were given with alloxan and per oral therapy with extract of  Dayak onion tuber 100 mg / kgbw, the treatment group 2 (P2) were given with alloxan and per oral therapy with extract of Dayak onion tuber 200 mg / kgbw and the treatment group 3 (P3) were given with alloxan and per oral therapy with extract of Dayak onion tuber 400 mg / kgbw. The therapy was given for 14 days, then the animals were sacrificed with ketamine and then its kidney was taken for examination of hisphatology in kidney. Observations based on their depiction of renal histopathology tubular degeneration and necrosis, glomerular necrosis, intestitial infiltration and glomerular sclerosis. Data obtained from the scoring of histopathological appearence albino rat kidneys were analyzed by test Kruskal-Wallis and if there is a real difference followed by Mann-Whitney test using SPSS 20.0 for windows. The results showed that the extract of Dayak onion tuber 400 mg/ kgbw  can reduce the degree of kidney damage in albino male rat exposed to alloxan significantly.  Key words: Eleutherine palmifolia, alloxan, kidney, histhopathology


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