Histologic study of testis injury after bisphenol A exposure in mice

2016 ◽  
Vol 33 (1) ◽  
pp. 36-45 ◽  
Author(s):  
Jijing Tian ◽  
Ye Ding ◽  
Ruiping She ◽  
Longhuan Ma ◽  
Fang Du ◽  
...  

The health effects of bisphenol A (BPA) have become a great concern in recent years. In this study, the reproductive toxicity of BPA was investigated. Male CD-1 mice were orally administrated with BPA (0, 100, 300 and 600 mg kg−1 body weight) for 56 consecutive days. Results showed that relative testis weight to total body weight was significantly lower in the high-dose group ( p < 0.01, p < 0.05). Microscopic examination under light and transmission electron microscopes showed disorders of spermatogenesis after BPA exposure, including rough basal lamina of seminiferous tubules and damage of tight junctions between Sertoli cells. Further study by terminal-deoxynucleoitidyl transferase–mediated nick end labelling assay showed a significant induction of apoptosis in the testis tissue of the BPA groups ( p < 0.01). Immunohistochemical study found that the expression of androgen-binding protein (ABP) was significantly decreased in BPA-treated mice ( p < 0.01). Our results indicated that impairment of the basal lamina of seminiferous tubules and tight junctions may contribute to BPA-induced cell injury. A decrease in the level of ABP could be the possible mechanism for the reproductive toxicity of BPA. These findings provided direct evidence and novel insight into the reproductive toxicity of BPA and may have implications for understanding the toxicity of other endocrine disruptors.

2021 ◽  
pp. 109158182098607
Author(s):  
Narendra S. Deshmukh ◽  
Shailesh Gumaste ◽  
Silma Subah ◽  
Nathasha Omal Bogoda

Palmitoylethanolamide (PEA) is an endogenous ethanolamine playing a protective and homeodynamic role in animals and plants. Prenatal developmental toxicity of PEA was tested following oral administration to pregnant female Wistar rats, from days 0 to 19 of gestation, at dosage of 250, 500, or 1,000 mg/kg body weight, according to Organisation for Economic Co-operation and Development Test Guideline No. 414. On gestation day 20, cesarean sections were performed on the dams, followed by examination of their ovaries and uterine contents. The fetuses were further examined for external, visceral, and skeletal abnormalities. Palmitoylethanolamide did not cause any alterations at any of the given dosages in the measured maternal parameters of systemic toxicity (body weight, food consumption, survival, thyroid functions, organ weight, histopathology), reproductive toxicity (preimplantation and postimplantation losses, uterus weight, number of live/dead implants and early/late resorptions, litter size and weights, number of fetuses, their sex ratio), and fetal external, visceral, or skeletal observations. Any alterations that were recorded were “normal variations” or “minor anomalies,” which were unrelated to treatment with PEA. Under the condition of this prenatal study, the no-observed-adverse-effect level of PEA for maternal toxicity, embryotoxicity, fetotoxicity, and teratogenicity in rats was found to be >1,000 mg/kg body weight/d. It indicates that PEA is well tolerated by and is safe to pregnant rats even at a high dose of 1,000 mg/kg body weight/d, equivalent to a human dose of greater than 9.7 g/d. This prenatal developmental toxicity study contributes greatly in building a robust safety profile for PEA.


1995 ◽  
Vol 14 (11) ◽  
pp. 889-894 ◽  
Author(s):  
N. Pant ◽  
AK Prasad ◽  
SC Srivastava ◽  
R. Shankar ◽  
SP Srivastava

1 Carbofuran was administered orally to adult male rats at dose levels of 0.1, 0.2, 0.4 or 0.8 mg kg -1 body weight, 5 d wk-1 for 60 days. A dose dependent decrease was observed in body weight of rats treated with 0.2-0.8 mg carbofuran kg -1 body weight 2 A significant decrease in the weight of epididymides, seminal vesicles, ventral prostate and coagulating glands was observed at various test doses of carbofuran except at the lowest dose. 3 Decreased sperm motility, reduced epididymal sperm count along with increased morphological abnormali ties in head, neck and tail regions of spermatozoa were observed in rats exposed to 0.2, 0.4, or 0.8 mg carbo furan kg-1 body weight. 4 In addition, significant alterations were observed in the activities of marker testicular enzymes viz. sorbitol dehydrogenase (SDH), glucose-6-P-dehydrogenase (G6PDH) (decreased), lactate dehydrogenase (LDH) and γ-glutamyl transpeptidase (γ-GT) (increased) depending on dose. 5 Histologically, the results indicated the toxicity of carbo furan on testes depending on dose. The changes pre dominantly consisted of moderate oedema, congestion, damage to Sertoli cells and germ cells, along with the accumulation of cellular debris and presence of giant cells in the lumen of a few seminiferous tubules which showed disturbed spermatogenesis with the higher doses of carbofuran. 6 These observations determined a no effect level dose of 0.1 mg kg-1 body weight of carbofuran on the biochemi cal and morphological indices studied for male repro ductive toxicity assessment in the rat model. The results of the present study provide first hand information on the reproductive toxicity of carbofuran in male rats.


2002 ◽  
Vol 50 (3) ◽  
pp. 365-371 ◽  
Author(s):  
L. Várnagy ◽  
P. Budai ◽  
E. Molnár ◽  

The reproductive toxicity of lead acetate and of a fungicide formulation (Dithane M-45) containing 80% mancozeb was studied on rats. Lead acetate was applied in the feed in the following dose groups: control, 1,000, 5,000 and 10,000 mg/kg of diet. The three treatment groups received, in addition to the above doses of lead acetate, 4,500 mg/kg Dithane M-45 in the diet. The method was based on the OECD Guideline for Testing of Chemicals No. 415 (1981). Clinical symptoms and mortality were not found in the parent generation. The body weight of female animals decreased significantly before the pregnancy period. This tendency was also seen in males after the combination treatment. At the two high dose levels a remarkable body weight increase was seen in the female animals during the lactation period. As a result of treatment, decreased body weight of offspring was measured during the lactation period. No gross pathological changes were seen. Histological examination showed general tubulonephrosis in the experimental animals. It can be established that the administration of Dithane M-45 did not enhance the reproductive toxicity of lead acetate.


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 6 (4) ◽  
pp. 635-640
Author(s):  
Emdadul Hoque ◽  
Khaled Mahmud Sujan ◽  
Md Suman Mia ◽  
Md Iqramul Haque ◽  
Afrina Mustari ◽  
...  

Bisphenol-A (BPA) is one of the highest volume chemicals produced world-wide and used in the manufacture of plastics and epoxy resins that are pervasive in our environment and daily lives. The present research was carried out to investigate the effects of two different doses of Bisphenol-A (BPA) on the body weight, hematological parameters and patho-physiological changes of kidney in mice. For this study, fifteen mice, 6 to 8 weeks of age with an average bwt 27.10±0.5 gm, were randomly divided into three groups (n= 5). Group A (control) received only normal mouse pellet while group B and group C received pellet mixed with BPA @ 50 mg and 100 mg / kg bwt daily for 12 weeks, respectively. At the end of the experiment, blood and tissues were collected and processed for hematological and histopathological examination. Results showed that BPA- treated mice caused significant elevation (p<0.01) in weight gain even treated with low dose (50mg) of BPA. The mice exposed to high dose of BPA (100 mg) showed marked reduction (p<0.05) in total erythrocyte count (TEC), significant decreased (p<0.01) in hemoglobin concentration (Hb) and packed cell volume (PCV). Histopathological alterations were detected in the kidneys of BPA-treated mice. In conclusion, this study suggested that BPA exerts deleterious impacts on hematological parameters including association with renal injuries. Asian J. Med. Biol. Res. December 2020, 6(4): 635-640


Author(s):  
Kaveh Khazaeel ◽  
Ammar Atashfaraz ◽  
Zhara Davoudi ◽  
Javad Jamshidian ◽  
Naeem Erfani Majd ◽  
...  

Background: Bisphenol A (BPA) is an endocrine-disrupting agent with a weak estrogenic effect. BPA causes testicular damage by reducing the activity of antioxidant enzymes. Bromelain (BROM) is a natural compound derived from pineapple, which is widely used as a dietary supplement with antioxidant properties. Objectives: The present study aimed to investigate the possible therapeutic effects of BROM on the testicular damage induced by BPA administration. Methods: This study was conducted on 40 adult male mice, which were divided into four groups of control (daily treatment with olive oil), BPA (600 mg/kg), BROM (70 mg/kg), and BPA + BROM. The treatments were administered orally for 35 consecutive days. Following that, the animals were euthanized by cervical dislocation, their testes were dissected, and morphometric evaluations (length, width, and thickness of testis) were performed. The epididymal tail was cut to release the sperms for sperm parameter assessment (count and motility). Afterwards, the testes were fixed in buffered formalin for histological examinations (number, diameter, and wall thickness of seminiferous tubules and the counts of spermatogenic, Sertoli, and Leydig cells). Results: All the indices of testicular morphology decreased significantly (P < 0.05) following BPA administration compared to the controls. In addition, the sperm parameters and Leydig and Sertoli cell counts indicated significant decremental effects on the animals administered with BPA compared to the controls (P < 0.05). After the administration of BROM in the BPA + BROM group, all the testicular morphometric indices increased significantly (P < 0.05) compared to the animals administered with BPA alone. These indices were the morphometric values of the testes, sperm parameters, cell counts, and seminiferous morphometric properties. Conclusions: According to the results, BROM could reduce the debilitative effects of BPA on the testes of the mice and protect the reproductive health of the animals against BPA-induced toxicity.


Author(s):  
Juan C. Cavicchia ◽  
Fabio L. Sacerdote

Pregnant rats (day 13) received 10mg/kg of Busulfan i.p. in order to deplete of germ cell the testes of the new born rats. The seminiferous tubules of their off spring from postnatal age 1 day up to day 35 were examined with TEM after fixation plus intercellular tracers, and with freeze-fracture techniques. During this period, the inter-Sertoli tight junctions of controls increase both in numbers and in length. Between days 10 and 13 the seminiferous cords have numerous preleptotene and leptotene spermatocytes (Fig.1) surrounded by tracer. The inter-Sertoli junctions are tortuous and predominantly perpendicular to the basal lamina. Between ages 13 and 20 days the seminiferous epithelium reaches zygotene-pachytene stages (fig.2) identified by the presence of synaptonemal complexes. The tracer is stopped at the inter-Sertoli junctions at this stage, whereas it still permeates tubules displaying preleptotene and leptotene spermatocytes.Freeze-fracture shows that the orientation of inter-Sertoli junctions has changed to parallel, both to each other and to the basal lamina (fig.3). In the Busulfan treated rats, the tubules continue having, up to postnatal day 30, only Sertoli cells and scanty spermatogonia.


1990 ◽  
Vol 2 (4) ◽  
pp. 321 ◽  
Author(s):  
C Soler ◽  
C Blazquez ◽  
J Pertusa ◽  
M Nunez ◽  
J Nunez ◽  
...  

Testis weight as a percentage of body weight did not change following bilateral ligation of the efferent ducts (EDL) close to the epididymis, whereas following removal of part of the epididymis between the site of ligation and a point close to the junction between the caput and corpus (PCE), testis weight first rose linearly until Day 4 and then showed an exponential decrease between Days 4 and 28. After EDL, the perimeter of the seminiferous tubules rose for the first 7 days and then remained elevated, whereas after PCE, there was a linear decrease between Days 4 and 28. Following EDL, the percentage of altered and degenerated tubular cross-sections rose to about 30% and 10%, respectively, during the first 7 days after operation and then remained constant; after PCE, the percentage of altered tubules reached a maximum of 54% by 4 days and then fell, whereas the percentage of degenerated tubules continued to rise to 95% by 28 days. It would appear that all the effects of removal of a portion of the epididymis cannot be explained by blockage of the excurrent ducts, and a specific endocrine effect of the epididymis on the testis is proposed.


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.


1973 ◽  
Vol 59 (3) ◽  
pp. 559-572 ◽  
Author(s):  
William B. Neaves

The permeability of Sertoli cell tight junctions to lanthanum administered during fixation has been compared in rats after ligation of the ductus deferens and after ligation of the ductuli efferentes. In both control and vasoligated testes, lanthanum penetrated only short distances into the Sertoli cell tight junctions before stopping abruptly. The tight junction, consisting of numerous pentalaminar fusions of contiguous Sertoli cell membranes, prevented diffusion of lanthanum into the adluminal compartment of the seminiferous epithelium. In rats with ligated ductuli efferentes, lanthanum completely permeated many Sertoli cell tight junctions and occupied intercellular spaces of the adluminal compartment. In spite of their newly acquired permeability to lanthanum, tight junctions retained characteristic ultrastructural features, including numerous membrane fusions. When lanthanum-filled tight junctions were sectioned en face, membrane fusions appeared as pale lines in lakes of electron-opaque tracer. These linearly extensive fasciae occludentes occasionally ended blindly, suggesting that lanthanum may have traversed the junction by diffusing around such incomplete barriers. The increased permeability of Sertoli cell tight junctions after efferent ductule ligation, which caused rapid testicular weight gain followed by atrophy, indicates that tight junctions are sensitive to enforced retention of testicular secretions inside the seminiferous tubules. The apparent normalcy of Sertoli cell tight junctions after vasoligation, which had no effect on testis weight, supports the view that blockage of testicular secretions distal to the epididymis is relatively innocuous.


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