197 DIFFERENTIAL EFFECTS OF FLUTAMIDE AND DI-(2-ETHYLHEXYL) PHTHALATE ON MALE REPRODUCTIVE ORGANS IN A RAT MODEL

2009 ◽  
Vol 21 (1) ◽  
pp. 197
Author(s):  
T. T. B. Vo ◽  
E.-M. Jung ◽  
M.-G. Back ◽  
V. H. Dang ◽  
K.-C. Choi ◽  
...  

Endocrine disruptors (EDs) with androgenic and anti-androgenic effects may alter reproductive function by binding to androgenic receptors (AR) and inducing or modulating AR-dependent responses in the male reproductive system. However, the molecular mechanism(s) underlying these events remains unclear. Thus, in the present study, we elucidated the prenatal effects of maternal testosterone propionate (TP), flutamide (Flu), and di-(2-ethylhexyl) phthalate (DEHP) on male reproductive organs of newborn rats. Pregnant Sprague-Dawley (n = 32 in total, n = 8/each group) rats were treated with these compounds at gestation days 11 to 21, and newborn males (n = 154 in total) were euthanized at post-neonatal day (PND) 63. Interestingly, maternal exposure to Flu or DEHP caused fluctuations in the neonatal levels of serum testosterone (T) and luteinizing hormone (LH). Serum T and LH were up-regulated by Flu, but these hormones were down-regulated by DEHP. The anogenital distances (AGD) of male newborns were detected at PND 1, 21, and 63. Male rats treated prenatally with DEHP (100 mg kg–1 mother’s body weight) or Flu showed an AGD shorter than that of control rats. At PND 63, the sperm concentration, viability, and mobility were reduced in the maternal DEHP and Flu-treated groups. The numbers of seminiferous tubules were reduced in the Flu- and DEHP-treated offspring when compared with vehicle- and TP-treated groups, and the tubules of the testes at PND 63 were disrupted by a high dose of Flu. In addition, we examined differential gene expression patterns in the testes by microarray analysis following ED exposure, particularly in sex determination-related genes. Significantly distinct expressions of sex determination-related genes were observed in the testes by microarray analysis following treatments with different types of EDs in this study. Although Flu and DEHP are considered to be identical with regard to their anti-androgenic effects, their effects on developing male reproductive organs were distinct, suggesting that Flu competes with endogenous T, while DEHP influences a different step in androgenesis.

ISRN Urology ◽  
2013 ◽  
Vol 2013 ◽  
pp. 1-10 ◽  
Author(s):  
Gulsah Bitgul ◽  
Isil Tekmen ◽  
Didem Keles ◽  
Gulgun Oktay

Objective. The aim of this study was to investigate protective effects of resveratrol, a strong antioxidant, against possible negative effects of chronic immobilization stress on testes of male rats histochemically, immunohistochemically, ultrastructurally, and biochemically. Material and Methods. Male Wistar rats were divided into 4 groups (n=7). Group I, control group (C), was not exposed to stress. Group II, stress group (S), was exposed to chronic immobilization stress. In Group III, low dose resveratrol + stress group (LRS), rats were given 10 mg/kg/day resveratrol just before the stress application. In Group IV, high dose resveratrol + stress group (HRS), rats were given 20 mg/kg/day resveratrol just before the stress application. For chronic immobilization stress application animals were put in the plastic tubes (6 cm in diameter, 15 cm in length) during 32 days for 6 hours. All animals were sacrificed 18 hours after the last stress application. Results. Histochemical and ultrastructural investigations showed that in stress group there was germ cell deprivation in seminiferous tubules and increase of connective tissue on interstitial area. No significant changes were seen in low and high dose resveratrol groups. After immunohistochemical investigations, TUNEL (+) and Active Caspase-3 (+) cells were increased in seminiferous tubules of stress group compared with those control group, but they were decreased in low and high dose resveratrol groups. According to biochemically results, MDA, GSH, and testosterone levels in stress group showed no significant difference when compared with those of the other groups. Conclusion. The chronic immobilization stress increases oxidative stress and apoptosis and causes histological tissue damages; resveratrol can minimize the histological damage in testes significantly.


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.


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.


2016 ◽  
Vol 2016 ◽  
pp. 1-10 ◽  
Author(s):  
Li Zhou ◽  
Qiuling Huang ◽  
Rong Wang ◽  
Jie Zhou ◽  
Aicui Ma ◽  
...  

Purpose. This study was aimed to investigate the reproductive toxicity of Zishen Yutai Pill (ZYP) on fertility and early embryonic development in rats. Methods. SD rats were randomly divided into 5 groups: vehicle control group (distilled water, i.g.), positive control group (80 mg/kg of cyclophosphamide, i.p.), and three ZYP-treated groups (3, 6, and 12 g/kg/d, i.e., 12x, 24x, and 48x clinical doses, i.g.). The high dose was set as the maximum gavage dosage. Results. Cyclophosphamide showed diverse hazards, such as decreased weight of male reproductive organs and sperm density (P<0.05). However, there were no obvious effects of ZYP on physical signs, animal behavior, and survival rate, as well as on weight and food intake during the premating and gestation periods. Importantly, there were no significant adverse effects of ZYP on indexes of copulation, fecundity and fertility indexes, weights and coefficients of male reproductive organs, epididymal sperm number and motility, estrous cycle, preimplantation loss rate, and implantation rate. Besides, the numbers of live and resorbed fetuses per litter were not significantly altered. Conclusions. ZYP had no reproductive toxicities on fertility and early embryonic development in rats at 48x equivalent clinical doses.


2009 ◽  
Vol 55 (4) ◽  
pp. 400-411 ◽  
Author(s):  
Thuy T. B. VO ◽  
Eui-Man JUNG ◽  
Vu Hoang DANG ◽  
Kikyung JUNG ◽  
Jounghee BAEK ◽  
...  

2019 ◽  
Vol 2 ◽  
pp. 107-109
Author(s):  
Lita Ayu Umartani ◽  
Aretasani Rahim ◽  
Halimah Asy Syahidah

The buffalo egret (Bubulcus ibis) belongs to the Ciconiiformes order, family Ardeidae. The buffalo egret (Bubulcus ibis) is the smallest egret (about 50 cm). Its body is slimmer than Blekoksawah (Ardeolaspeciosa), although not as large as egrets. All feathers are white, but during the mating season the feathers on the head, neck, back and chest are yellow. Reproductive organs are the ke y to success in maintaining new offspring. Male reproductive organs will produce male sex cells or living spermatozoa. It is important to do research on anatomy and histology to determine the maturity of the reproductive organs of the bird. The purpose of this study was to determine the anatomical and histological structure of male reproductive organs of buffalo egrets (Bubulcus ibis). The method used for histology is the paraffin method with Hematoxylin-Eosin staining. The data analysis technique uses descriptive analysis for histological preparations. Anatomical observations include the color, shape and location of the reproductive organs, while histological observations of the structure of the reproductive organs using a microscope. The results of the study were anatomically pale-colored testicle. The location of the testicles is on ventral from the most cranial lobe. While the histological structure of the testis of the Buffalo Egret (Bubulcus ibis) consisted of spermatozoa, lumen, stereosilia, ephitelium of eididymis and seminiferous tubules.


2024 ◽  
Vol 84 ◽  
Author(s):  
C. Chaimontri ◽  
S. Iamsaard

Abstract Although Dolichandrone serrulata flower (DSF) aqueous extract has been shown to possess pharmacological properties, its systemic toxicity has still to be evaluated. The present study aimed to investigate the sub-chronic toxicity effect of DSF extract on biochemical parameters and histological structures of liver, kidney, testis, and epididymis plus vas deferens. Adult male rats were administered DSF at 100, 300, and 600 mg/kgBW via oral gavage for 48 consecutive days while control rats received distilled water. At the end of the experiment, blood, liver, kidney, testis, and epididymis plus vas deferens samples were collected to determine any changes to serum biochemical components including ALT, ALP, and creatinine levels and histological structures. The results revealed no significant difference in body weight and food or water consumption between control and the DSF-treated groups. It was found that DSF significantly increases the weight of epididymis plus vas deferens, while the kidney and liver showed a decrease in the high dose group (P value < 0.05). Histological changes in these vital and reproductive tissues including fibrosis were not observed after administration but ALT, ALP, and creatinine levels were significantly altered in the treated groups (P value < 0.05). These altered levels, however, were still within normal ranges. In conclusion, these findings demonstrated that D. serrulata flower extract had no sub-chronic toxicity on vital and reproductive structures but slightly altered some liver and kidney functions.


MEDISAINS ◽  
2020 ◽  
Vol 18 (2) ◽  
pp. 52
Author(s):  
Ave Olivia Rahman ◽  
Anati Purwakanthi ◽  
Hasna Dewi

Background: Betel nut (Areca catechu L) are traditional beverages in Jambi. Betel nut high dose has a cytotoxic effect on testis and other organs—limited data about the effect of betel nut as male antifertility.Purposes:  This study aimed to determine the effect of infertility on betel nut use at a dose of 50 mg/kg body weight (BW) in male rats.   Methods: Ten male Sprague Dawney rats that had passed the fertility test, aged 2-3 months and weighing 150-200 grams ware used in this study. The rat was grouped into two groups randomly. Group 1, as the negative control, were received aqua dest, and group 2 was treated by betel nut with dose 50 mg/kg BW for 35 days. When terminated, testis weight weighed using micro scales. Blood collected for measuring testosterone levels. Histopathology assessment of testis used Hematoxylin Eosin Staining and sperm counting from cauda epididymis.Results: The weight of testis in the group received betel nut was lower than the control group. The histopathology of testis showed shrunk, reduced the diameter of seminiferous tubules, and like cytolytic lesions in the germinal layer—the total sperm number and progressive sperms also lower than the control group (p<0.05). There was no abnormality in Leydig cell and interstitium tissue.  Male rats after treatment could not impregnate the female rats.Conclusion: Betel nut at dose 50 mg/kg BW have antifertility activity in male rats.


2017 ◽  
Vol 5 (2) ◽  
pp. 72 ◽  
Author(s):  
Mossad El-Sayed ◽  
Mohamed Kandiel ◽  
Dalia Ebied

This study aimed to evaluate the numerous azithromycin (as a member of macrolides) effects on the male reproductive organs, spermio-gram, testicular oxidative stress markers of adults’ male albino rats. Azithromycin was administered orally once daily to male rats (200-250 b.wt.) at a dose of 45 mg (therapeutic) or 90 mg/kg b.wt. (double-therapeutic) for three or six days and scarified at the first, thirty and sixty days after the last dose of administration. A significant decrease as the index weight of the reproductive organs as well as sperm motility, livability and cell concentration, but sperm abnormalities increased at varying times post-treatment with azithromycin administration. Testosterone hormone level did not vary significantly after azithromycin dosing for three days along the experimental period. However, it differed at the first day after the end of azithromycin dosing for six days. The intra-testicular oxidative stress alteration mostly occurred at the thirty-day post-treatment in the three- and six-days protocols. In the three-days protocol, there was a significant decrease in malondialdehyde level and superoxide dismutase enzyme activity in a double-therapeutic group. In the six-days regimen, there was an increased activity of catalase enzyme, accompanied with a significant decrease in malondialdehyde levels as well as glutathione peroxidase enzymes. Double therapeutic dose for six days’ treatment was associated with vascular congestion and perivascular inflammatory cells and ho-mogenous eosinophilic material infiltration into the stroma of testes. The lumen of seminiferous tubules and epididymis showed azoo-spermia. From these results, it could be concluded that azithromycin administration has hazard effects on male adult’s rats’ fertility governed with the spermiogram, oxidative stress and the histopathological alternations during the post-treatment period.


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