Reproductive toxicity of cadmium in pubertal male rats induced by cell apoptosis

2021 ◽  
pp. 074823372110226
Author(s):  
Lingna Yi ◽  
Juan Dai ◽  
Yong Chen ◽  
Yeqing Tong ◽  
You Li ◽  
...  

Cadmium (Cd) is a heavy metal that is widely present in modern industrial production. It is a known, highly toxic environmental endocrine disruptor. Long-term exposure to Cd can cause varying degrees of damage to the liver, kidney, and reproductive system of organisms, especially the male reproductive system. This study aimed to explore the mechanism of Cd toxicity in the male reproductive system during puberty. Eighteen healthy 6-week-old male Sprague–Dawley rats were randomly divided into three groups (control group, low-dose group, and high-dose group) according to their body weight, with six in each group. Cd (0, 1, and 3 mg/kg/day) was given by gavage for 28 consecutive days. The results showed that Cd exposure to each dose group caused a decrease in the testicular organ coefficient and sperm count, compared with the control group. Cd exposure resulted in significant changes in testicular morphology in the 3 mg/kg/day Cd group. In the 1 and 3 mg/kg/day Cd groups, serum testosterone decreased and apoptosis of testicular cells increased significantly ( p < 0.05). In addition, compared with the control group, the activity of glutathione peroxidase and superoxide dismutase in each Cd exposure dose group decreased, but the content of malondialdehyde in the high-dose, 3 mg/kg/day Cd treatment group significantly increased ( p < 0.05). Although Cd exposure caused an increase in the messenger RNA (mRNA) levels of Bcl-2, Caspase-3 and Caspase-9 in the testicular tissues ( p < 0.05), Bcl-2 expression was unchanged ( p > 0.05). The expression level of Akt mRNA in testicular tissue of rats in the high-dose 3 mg/kg/day Cd group was increased ( p < 0.05). Our data suggest that Cd affected testosterone levels, and apoptosis was observed in spermatids.

Author(s):  
Davoud Kianifard ◽  
Seyyed Maysam Mousavi Shoar ◽  
Morteza Fallah Karkan ◽  
Ahmed Aly

Background: Quinine (QU) as an anti-malarial drug induces alterations in testicular tissue. Toxic effects of monosodium glutamate (MSG) on the male reproductive system have been recognized. Objective: To investigate the impact of MSG administration on the intensity of gonadotoxicity of QU. Materials and Methods: Sixty eight-wk old Wistar rats weighing 180-200 gr were divided into six groups (n = 10/each): the first group as a control; the second and third groups received low and high doses of MSG (2 & 4 gr/kg i.p.), respectively, for 28 days; the fourth group received QU for seven days (25 mg/kg); and in the fifth and sixth groups, QU was gavaged following the MSG administration (MSG + QU) from day 22 to day 28. Serum testosterone and malondialdehyde (MDA) levels were measured. Testes samples were prepared for tissue MDA levels, histomorphometry, and immunohistochemistry of p53. Sperm analysis was performed on cauda epididymis. Results: Serum and tissue MDA levels were increased in treated groups compared to the control group. This increment was higher in the MSG + QU groups. The testosterone levels were reduced significantly (p < 0.0001) in all treated groups. In addition, histomorphometric indices and tubular epithelium population were reduced significantly (p < 0.0001) in QU, MSG + QU, and consequently in high-dose MSG, QU, MSG + QU groups. All spermatogenic indices were reduced in the treated groups, particularly in the MSG + QU groups. Sperm motility and viability indices were reduced significantly (p = 0.003) in the MSG + QU groups. Finally, the overexpression of p53 was observed in the MSG + QU groups. Conclusion: The administration of MSG before and during QU therapy may intensify testicular tissue alterations. Key words: Male reproductive system, Monosodium glutamate, Quinine hydrochloride, Rat.


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.


2020 ◽  
Vol 44 (2) ◽  
pp. 92-98
Author(s):  
Hadeel B. Al-Sabaawy ◽  
Bushra I. Al-Kaisie

In recent years, fluorosis caused many problems in humans and animals bodies. Dental fluorosis, skeletal fluorosis, bone fractures, decreased birth rates, adverse effects on the male genital system, like damaging the structure of testes and epididymis and loosing fertilization ability can be considered as good examples of fluorosis. Thus, the current study aimed to determine the toxicity of sodium fluoride (NaF) on the activity of sperm and the level of sex hormones including testosterone, follicle stimulating hormone, and luteinizing hormone. For achieving this purpose, thirty adult albino male rats, aged between 90-100 days, were divided randomly into two treated groups with 10 rats for each group which were treated with 150, 300 ppm of sodium fluoride,respectively. In addition, 10 rats were kept as a control group. Sodium fluoride was offered to the treated groups in the drinking water to evaluate the toxic effect of NaF on male reproductive system, sperm concentration, sperm motion, and sperm velocity compared with control group. The findings revealed a significant decrease in the sperm concentration, sperm count, sperm motion, sperm velocity and the level of sexual hormones in comparison with the control group. It can be concluded that NaF may reduce the efficiency of male reproductive system, and reduce the levels of sexual hormones in rats


2012 ◽  
Vol 36 (1) ◽  
pp. 68-74
Author(s):  
Fakhrildin, M-B. M-R.

Carnitine is quaternary ammonium compound and required for the transport of fatty acids from the cytosol into the mitochondria for the generation of metabolic energy. The aims of the present study were to assess the effects of L-carnitine administration to pregnant mice on some parameters of reproductive performance and pregnancy outcome.One hundred and five pregnant female mice Swiss albino strain mice age: 12-14 weeks were used in this study. Pregnant mice were divided randomly into three equal groups including control group (administered distilled water; DW), low dose group (T1) administered 0.5 mg/Kg L-carnitine and high dose group (T2) administered 1 mg/Kg L-carnitine. Daily administration of D.W. or L-carnitine was continued from day 1 (day post-sexual mating) until parturition. Hormone assay involving follicle stimulating hormone (FSH), luteinizing hormone (LH) and estradiol (E2), litter size, percentage of female sex, weight of the reproductive system and endometrial thickness were assessed.Assessment of levels of serum reproductive hormones appeared that the FSH and LH and E2 for both treated groups were increased significantly (P<0.05) as compared to the control group. Moreover, significant increment (P<0.05) in the weight of reproductive system, litter sizes and a significant increment (P<0.05) in the thickness of endometrium for both treated groups was observed as compared to the control group.Conclusion: administration of 0.5 mg/Kg L-carnitine to pregnant mice had beneficial effects on pregnancy and offspring outcomes.


PeerJ ◽  
2019 ◽  
Vol 7 ◽  
pp. e7039
Author(s):  
Lin Wang ◽  
Jie Xu ◽  
Feng Zeng ◽  
Xiangjun Fu ◽  
Weihong Xu ◽  
...  

Objective Environmental endocrine disruptors (EEDs) with a weak ability to mimic estrogen have been associated with thyroid dysfunction. However, little is known about the effect of nonylphenol (NP), a well-known EED, on thyroid structure. The present study evaluates whether gestational and lactational exposure to NP impacts growth and thyroid structure in F1 male rats. Methods A total of 60 rats were gavaged with NP (25, 50, and 100 mg/kg), estradiol (E2, 30 μg/kg/day), and corn oil alone (vehicle control) from gestational day 6 to postnatal day (PND) 21. Serum thyroid hormones free triiodothyronine (FT3), free thyroxine (FT4) and thyroid stimulating hormone levels were detected by automated chemiluminescence immunoassay analyzer. The NP level in the thyroid was measured using high-performance liquid chromatography. The ultrastructure of follicular epithelial cells was examined using transmission electron microscopy. Histopathology was conducted using hematoxylin and eosin staining. Results On PND 0, exposure to 50 and 100 mg/kg/day NP led to a significant decrease in the average litter size, litter weight and number of live pups per litter compared to the control group (P < 0.05). Dams exposed to NP during perinatal period demonstrated decreased serum levels of FT3 and FT4 in F1 male rats, when compared to the control group (P < 0.05). The NP level in the control group was 3.39 ± 0.08 ng/mg, while NP levels in the low, middle, and high dose groups ranged from 5.20 to 11.00 ng/mg. Exposure caused a dose-related increase in NP level in the thyroid of male pups (P < 0.01). The thicknesses of the thyroid follicular epithelium were 2.06 ± 0.37 μm in the control group and 3.97 ± 1.61 μm in the high-dose group. The thickness of the thyroid follicular epithelium increased with an increase in treatment dose in a dose-dependent manner (P < 0.05). The sizes of the thyroid follicles were 1,405.53 ± 866.62 μm2 in the control group and 317.49 ± 231.15 μm2 in the high-dose group. With increasing NP dosages, animals showed a decreased size of the thyroid follicle (P < 0.01). Thyroid follicular cells of NP-treated rats showed mildly swollen mitochondria and dilated rough endoplasmic reticulum in the cytoplasm. Conclusion Nonylphenol can cross the placental barrier and accumulate in the thyroid of F1 male rats. Gestational and lactational exposure to NP in dams impacted both development and growth of pups and damaged the ultrastructure of their thyroid tissue, which may further negatively influence normal thyroid function.


1990 ◽  
Vol 9 (1) ◽  
pp. 79-91 ◽  
Author(s):  
D. L. Morgan ◽  
J. R. Bucher ◽  
J. E. Huff ◽  
J. K. Haseman ◽  
S. L. Eustis ◽  
...  

3,3′-Dimethoxybenzidine dihydrochloride (DMOB) was evaluated for chronic toxicity and carcinogenicity because benzidine, a structurally related chemical, is a known human carcinogen, and because of potential human exposure during production of bisazobiphenyl dyes. Previous carcinogenicity studies of DMOB were considered to be inadequate. Toxicology and carcinogenesis studies were conducted by administering 0,80,170, or 330 ppm DMOB (>97.5% purity) in drinking water to groups of F344/N rats for 21 months. Seventy rats of each sex were used in the control group, 45 in the low-dose, 75 in the mid-dose, and 70 in the high-dose group. Ten rats of each sex in the control and 330 ppm dose groups were evaluated after 9 months. After exposure for 9 months, chemical-related neoplastic effects included liver foci, carcinoma of the preputial gland in one male, carcinoma of the clitoral gland in one female, and carcinoma of the Zymbal gland in two male rats. Although designed for 24 months, these studies were terminated at 21 months because significant numbers of exposed rats died with tumors or were sacrificed in moribund condition. Chemical-related nonneoplastic effects were hematopoietic cell proliferation in the spleen, and cystic and centrilobular degeneration and necrosis of the liver. 3,3′-Dimethoxybenzidine was clearly carcinogenic for male and female F344/N rats. After exposure for up to 21 months, significantly increased incidences of neoplasms were observed in multiple sites: skin, Zymbal gland, preputial and clitoral glands, oral cavity, small and large intestines, liver, brain, mesothelium, mammary gland, and uterus of treated rats.


2021 ◽  
Vol 12 (1) ◽  
pp. 357-365
Author(s):  
Bassam Abdulaziz Alahmadi

Cancer treatments can affect sperm production and a significant percentage of cancer patients may develop permanent azoospermia or severe oligozoospermia after chemotherapy. To investigate the influence of Gemcitabine toxicity on the reproductive system of albino male rats (sperm count and morphology). An experimental animal study conducted in the zoology department, College of Science, King Saud University during the period from June to October 2014 using albino rats (Rattusnorvegicus) (Wistar strain). Males were divided into four different groups (control" 0 mg/kg",7 mg/kg,14 mg/kg, and 21 mg/kg). The reproductive organs, testicles and epididymis decreased in weight and atrophied in most of the animals treated with the drug in various doses. The mean absolute and relative epididymal weights were also significantly decreased. In the drug-effects recovery group, neither the testicles nor the epididymis in the animals treated with the three doses recovered fully normal weight. The testis's efficiency in producing sperm was significantly decreased at all doses. In the recovery group, the testis regained its efficiency, as no significant difference was recorded between the drug-treated groups and the control group. The drug caused complete loss of sperm, in a rat treated with the big dose. Gemcitabine caused a significant increase in the percentage of deformed sperms in all treated animals. Gemcitabine drug has high toxicity on the reproductive system of rats with a dose tenth of human dose, with a massive decrease in the count and quantity of sperm, which means that this drug can have more toxicity effects on human.


2016 ◽  
Vol 33 (2) ◽  
pp. 133-146 ◽  
Author(s):  
Müfide Aydoğan Ahbab ◽  
Nurhayat Barlas ◽  
Gözde Karabulut

The aim of the present study was to assess and compare the individual adverse effects of bisphenol A (BPA) and octylphenol (OP) on the reproductive system of prepubertal male rats. Rats were exposed to BPA and OP at doses of 125 and 250 mg/kg/day, by gavage, for 90 days. At the end of the study, the testes, epididymis, prostate gland, and seminal vesicle were removed and examined histopathologically. Also, 3-β-hydroxysteroid dehydrogenase expressions were analyzed and serum testosterone and luteinizing hormone (LH) levels were measured. Sperm head count of caput epididymis was performed using a hemocytometer. Seminiferous and epididymal round tubules were evaluated for tubule diameter, lumen diameter, and height of tubule epithelium. There were significant increases in relative testes weights in BPA125, OP125, and OP250 groups compared with the control. Atrophic tubules, pyknotic tubules, combined tubules, congestion, vacuolization of Sertoli cell, cell debris in the lumen, tubules without sperm, and degeneration of tubules were noted in the tissue specimens obtained from the treatment groups compared with the control group. Sperm head counts were decreased in all treatment groups except for the low-dose BPA group. Testosterone (T) levels decreased in the BPA and high-dose OP treatment groups. LH levels increased in BPA treatment groups and the low-dose OP treatment group and decreased in the high-dose OP group. Epithelial height of high-dose BPA and OP treatment groups increased compared with the control group. Furthermore tubular height of low-dose BPA and high-dose OP groups increased with respect to control levels. In the OP250 treatment group, thyroxine hormone level was increased compared to other groups. Also, in the OP125 treatment group, triiodothyronine hormone level was increased compared with other groups. The results of this study showed that BPA and OP affect the steroidogenic enzyme expression and T production in Leydig cells. In conclusion, BPA and OP have adverse effects on the male reproductive system of prepubertal rats.


2019 ◽  
Vol 17 (1) ◽  
pp. 1328-1338
Author(s):  
Yufeng Xing ◽  
Chuantao Zhang ◽  
Fenfen Zhai ◽  
Tianran Zhou ◽  
Xiang Cui ◽  
...  

AbstractCells with non-alcoholic fatty liver disease (NAFLD) were studied to determine the mechanism of liver deficiency via the AdipoR2-PPARa pathway. NAFLD cells were randomly divided into a normal control group, blank control group, model group, low dose group, medium dose group, and high dose group. The NAFLD models were established by incubating the cells with linoleic acid (LA) and palmitic acid (PA) (2:1) for 24 h. The test groups were incubated with different doses of Shugan Xiaozhi Fang extract. The pathological changes in cells that accumulated lipids were detected by Oil Red O staining. Malondialdehyde (MDA) and triglyceride (TG) levels were measured. The apoptosis of cells was evaluated by flow cytometry. The levels of AdipoR2, PPARa, CD36, acyl-CoA mRNA, and protein were confirmed by RT- PCR and Western blot. The results of the Oil Red O staining demonstrated that the NAFLD cell model was successfully established. Compared with the model group, the levels of TG and MDA in the groups that received low, medium, and high doses of Shugan Xiaozhi were significantly lower (P<0.01), and a dose effect was evident. In addition, the expression of AdipoR2, PPARa, CD36, acyl-CoA protein, and mRNA in the Shugan Xiaozhi-treated groups was upregulated. Furthermore, the levels of AdipoR2, PPAR, CD36, acyl-CoA protein, and mRNA in all drug treatment groups that were extracted from L-O2 normal human hepatocytes were significantly upregulated (P<0.01). Moreover, the factor pattern of HepG2 human liver carcinoma cells was similar to that of L-O2. The levels of AdipoR, CD36, acyl-CoA, and AdipoR mRNA in the HepG2 low group were increased (P<0.05). AdipoR, PPAR, CD36, and acyl-CoA protein levels and AdipoR mRNA expression were significantly increased in the intermediate dose group and high dose group (P<0.01). Shugan Xiaozhi Fang attenuates hepatic lipid deposition in NAFLD induced by incubating with LA and PA for 24 h, which is associated with the activation of the AdipoR2-PPARα pathway.


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