scholarly journals Peritubular macrophages and spermatogonia are sequentially increased in the testis of rats after mono-(2-ethylhexyl) phthalate exposure

2019 ◽  
Author(s):  
Ross Gillette ◽  
Richa Tiwary ◽  
Jorine JLP Voss ◽  
Shavini N Hewage ◽  
John H Richburg
Keyword(s):  
Corn Oil ◽  
Male Rats ◽  
Acute Injury ◽  
Seminiferous Tubules ◽  
Mhc Ii ◽  
Cell Niche ◽  
Testicular Injury ◽  
Phthalate Metabolite ◽  
Ethylhexyl Phthalate ◽  
Testicular Inflammation

AbstractPeripubertal exposure to the phthalate metabolite mono-(2-ethylhexyl) phthalate (MEHP) in rodents causes testicular inflammation, spermatocyte apoptosis, and disruption of the blood-testis barrier. The MEHP-induced inflammation response includes an infiltration of macrophages and neutrophils to the testes, although the cause and purpose of this response is unknown. Recently, a population of testicular macrophages phenotypically distinct from those resident in the interstitium was described in mice. Testicular peritubular macrophages aggregate near the spermatogonial stem cell niche and are believed to stimulate their differentiation. We hypothesized that if testicular peritubular macrophages do indeed stimulate spermatogonial differentiation, MEHP exposure would result in an increase of peritubular macrophages to stimulate the replacement of lost spermatocytes. Male rats were exposed to 700 mg/kg MEHP or corn oil (vehicle control) via oral gavage at PND 28 and euthanized at 48 hours, 1 week, or 2 weeks later. Tubules were stained with immunofluorescent markers for macrophages and undifferentiated spermatogonia. Peritubular macrophages were observed in rat testis similar to those previously described in mice: MHC-II+ cells on the surface of seminiferous tubules with heterogeneous morphology. Quantification of MHC-II+ cells revealed that, unlike in the mouse, their numbers did not increase through puberty. MEHP increased macrophage presence by six-fold 48-hours after exposure and remained elevated by two-fold two weeks after exposure. An increase of differentiating spermatogonia occurred two weeks after MEHP exposure. Taken together, our results suggest that peritubular macrophages play a crucial role in the testis response to acute injury and the subsequent recovery of spermatogenesis.Summary SentencePhthalate-induced testicular injury results in an increase of specialized peritubular macrophages that may assist in the recovery of spermatogenesis.

New approach for reproductive toxicity assessment: chromatoid bodies as a target for methylmercury and polychlorinated biphenyls in prepubertal male rats

2020 ◽  
Vol 32 (10) ◽  
pp. 914
Author(s):  
M. S. Garcia ◽  
W. A. Orcini ◽  
R. L. Peruquetti ◽  
J. E. Perobelli
Keyword(s):  
Corn Oil ◽  
Morphological Changes ◽  
Synergistic Effects ◽  
Reproductive Toxicity ◽  
Treated Group ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Control Group ◽  
High Dose ◽  
Long Term Effects

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.

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 ◽  
...  
Keyword(s):  
Sex Determination ◽  
Microarray Analysis ◽  
Expression Patterns ◽  
Reproductive Organs ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
High Dose ◽  
Total N ◽  
Male Reproductive Organs ◽  
Ethylhexyl Phthalate

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.

scholarly journals Effect of Thymus vulgaris leaf extract on cadmium-induced testicular toxicity in rats

2021 ◽  
Vol 45 (1) ◽  
Author(s):  
Remigius Ibe Onoja ◽  
Chinwe Uzoma Chukwudi ◽  
Emmanuel Uchechukwu Ugwueze ◽  
Davinson Chuka Anyogu ◽  
Wilson Obidah ◽  
...  
Keyword(s):  
Leaf Extract ◽  
Sperm Count ◽  
Treated Group ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Thymus Vulgaris ◽  
Testicular Toxicity ◽  
Histological Changes ◽  
Ameliorative Effect ◽  
Testicular Injury

Abstract Background Cadmium (Cd) is a known metallohormone which mimics the action of steroid hormones with adverse effect on testicular function. It is highly toxic and a prevalent environmental contaminant with no conventional antidote. This study investigates the possible ameliorative effects of Thymus vulgaris extract on testicular toxicity induced by Cd in male rats. Results The testicular and epididymal weights, serum concentration of follicle stimulating hormone, luteinizing hormone, and testosterone were significantly (p ≤ 0.05) lower in the cadmium-treated group compared to the control. Necrosis of germ cells of the seminiferous tubules was observed in the testicular tissues of the cadmium-treated group. Administration of extract showed mild but non-significant (p ≥ 0.05) protective effect on the cadmium-induced decrease in sex hormones and sperm count as well as oxidative stress and histological changes. Conclusion Thymus vulgaris leaf extract had weak ameliorative effect on cadmium-induced testicular injury in rats but with promising antioxidant activity.

scholarly journals Effects ofNigella sativa(Habbatus sauda) Oil and Nicotine Chronic Treatments on Sperm Parameters and Testis Histological Features of Rats

2014 ◽  
Vol 2014 ◽  
pp. 1-7 ◽  
Author(s):  
Ng Cho Ping ◽  
Noor Hashida Hashim ◽  
Durriyyah Sharifah Hasan Adli
Keyword(s):  
Body Weight ◽  
Sperm Motility ◽  
Seminiferous Tubule ◽  
Corn Oil ◽  
Sperm Quality ◽  
Sperm Parameters ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Sprague Dawley ◽  
Histological Features

Twenty-fourSprague-Dawleymale rats (7–9 weeks old, 200–250 g) were divided into Nicotine (N) (0.5 mg/100 g body weight (BW), Nicotine Control (NC) (saline, 0.1 mL/100 g BW),Habbatus saudaoil (HS) (6.0 μL/100 g BW), andHabbatus saudaControl (HSC) (corn oil, 0.1 mL/100 g BW) groups and treated for 100 days. Sperm parameters and seminiferous tubules measurements were evaluated. The N showed a significantly lower sperm motility (1.03±0.05×106 sperm/mL) and percentage of normal (82.61±0.03%) and live (93.88±0.01%) sperm, higher value for the seminiferous tubule (253.36±1.83 μm) and lumen (100.15±2.38 μm) diameters and spermatogonia (19.85±0.39 μm) and spermatocytes (33.37±0.59 μm) layers, and thinner spermatid-sperm layer (22.14±0.71 μm) than the NC (P<0.05). The HS had significantly higher sperm motility (1.49±0.04×106 sperm/mL) and percentage of normal (90.61±0.01%) and live (96.98±0.01%) sperm, smaller lumen diameter (67.53±2.34 μm) and thinner spermatogonia (17.67±0.32 μm) and wider spermatid-sperm (36.95±0.79 μm) layers than the HSC (P<0.05). This research confirmed that nicotine reduced sperm motility and morphology of normal and live sperms and also affected the testis histology, whileHabbatus saudaoil increased sperm quality and gave better testis histological features.

scholarly journals Overexpression of miR-506-3p Aggravates DBP-Induced Testicular Oxidative Stress in Rats by Downregulating ANXA5 via Nrf2/HO-1 Signaling Pathway

2020 ◽  
Vol 2020 ◽  
pp. 1-13
Author(s):  
Min Tang ◽  
Lei Zhang ◽  
Zheng Zhu ◽  
Ran Li ◽  
Shangqian Wang ◽  
...  
Keyword(s):  
Oxidative Stress ◽  
Signaling Pathway ◽  
Male Rats ◽  
Adolescent Male ◽  
Seminiferous Tubules ◽  
Stress Injury ◽  
Oxidative Stress Injury ◽  
Testicular Injury

Background. Di-N-butylphthalate (DBP) is a kind of unique endocrine toxicity linked to hormonal disruptions that affects the male reproductive system and has given rise to more and more attention. However, the mechanism of DBP-induced testicular injury remains unclear. Here, the objective of this study was to investigate the potential molecular mechanism of miR-506-3p in DBP-induced rat testicular oxidative stress injury via ANXA5 (Annexin A5)/Nrf2/HO-1 signaling pathway. Methods. In vivo, a total of 40 adolescent male rats were treated from 2 weeks with 800 mg/kg/day of DBP in 1 mL/kg corn oil administered daily by oral gavage. Among them, some rats were also injected subcutaneously with 2 nmol agomir-506-3p and/or 10 nmol recombinant rat ANXA5. The pathomorphological changes of testicular tissue were assessed by histological examination, and the antioxidant factors were evaluated. Subsequently, ANXA5, Nrf2, and its dependent antioxidant enzymes, such as HO-1, NQO1, and GST, were detected by Western blotting or immunohistochemical staining. In vitro, TM3 cells (Leydig cells) were used to detect the cell activity by CCK-8 and the transfection in the DBP-treated group. Results. Differentially expressed miRNAs between the DBP-treated and normal rats were analyzed, and qRT-PCR showed miR-506-3p was highly expressed in testicular tissues of the DBP-treated rats. DBP-treated rats presented severe inflammatory infiltration, increased abnormal germ cells, and missed cell layers frequently existed in seminiferous tubules, resulted in oxidative stress and decreased testicular function. Meanwhile, upregulation of miR-506-3p aggravated the above changes. In addition, miR-506-3p directly bound to ANXA5, and overexpression of miR-506-3p could reduce the ANXA5 expression and also decrease the protein levels of Nrf2/HO-1 signaling pathway. Additionally, we found that recombinant rat ANXA5 reversed the DBP-treated testicular oxidative stress promoting injury of miR-506-3p in rats. In vivo results were reproduced in in vitro experiments. Conclusions. This study provided evidence that miR-506-3p could aggravate the DBP-treated testicular oxidative stress injury in vivo and in vitro by inhibiting ANXA5 expression and downregulating Nrf2/HO-1 signaling pathway, which might provide novel understanding in DBP-induced testicular injury therapy.

scholarly journals MEHP-induced rat testicular inflammation does not exacerbate germ cell apoptosis

Reproduction ◽  
2018 ◽  
Vol 156 (1) ◽  
pp. 35-46 ◽  
Author(s):  
Jorine J L P Voss ◽  
Angela R Stermer ◽  
Rashin Ghaffari ◽  
Richa Tiwary ◽  
John H Richburg
Keyword(s):  
Germ Cell ◽  
Immune Cells ◽  
Neutrophil Infiltration ◽  
Inflammatory Monocytes ◽  
Cell Antibody ◽  
Infiltrating Cells ◽  
Fischer Rats ◽  
Testicular Injury ◽  
Ethylhexyl Phthalate ◽  
Testicular Inflammation

The testis is an organ that maintains an immune suppressive environment. We previously revealed that exposure of pre-pubertal rats to an acute dose of a well-described Sertoli cell toxicant, mono-(2-ethylhexyl) phthalate (MEHP), leads to an accumulation of CD11b+ immune cells in the testicular interstitial space that closely correlates with a robust incidence of germ cell (GC) apoptosis. Here, we test the hypothesis that the infiltrating immune cells contribute to GC apoptosis. Postnatal day 28 Fischer rats that received an oral dose of 700 mg/kg MEHP showed a significant infiltration of both CD11bc+/CD68+/CD163− macrophages and neutrophils. The infiltration peaked at 12 h, but had reduced by 48 h. Testicular macrophages from MEHP-treated rats showed significantly upregulated expression of Tnfa and Il6, and the Arg1/Nos2 ratio was reduced compared to controls. However, small increases in anti-inflammatory genes Il10 and Tgfb1 were also observed. Depletion of circulating monocytes with clodronate liposomes prior to MEHP treatment reduced the macrophage influx into the testis, but did not lower GC apoptosis. Additionally, depletion of neutrophils using an anti-polymorphonuclear cell antibody prevented both macrophage and neutrophil infiltration into the testis, and also did not affect GC apoptosis. Together, these results show that exposure to MEHP leads to a rapid and temporary influx of pro-inflammatory monocytes and neutrophils in the interstitium of the testis. However, with this acute dosing paradigm, these infiltrating leukocytes do not appear to contribute to MEHP-induced testicular GC apoptosis leaving the functional significance of these infiltrating cells in the pathogenesis of MEHP-induced testicular injury unresolved.

Urinary di(2-ethylhexyl)phthalate metabolite ratios in obese children of South Korea

2021 ◽  
Author(s):  
Jiwon On ◽  
Shin-Hye Kim ◽  
Jeongae Lee ◽  
Mi Jung Park ◽  
Sang-Won Lee ◽  
...  
Keyword(s):  
South Korea ◽  
Obese Children ◽  
Phthalate Metabolite ◽  
Ethylhexyl Phthalate

Evaluation of Reproductive Development Following Intravenous and Oral Exposure to DEHP in Male Neonatal Rats

2003 ◽  
Vol 22 (3) ◽  
pp. 159-174 ◽  
Author(s):  
Jon N. Cammack ◽  
Randy D. White ◽  
Donovan Gordon ◽  
Jerome Gass ◽  
Lawrence Hecker ◽  
...  
Keyword(s):  
Sperm Count ◽  
Liver Weight ◽  
Oral Exposure ◽  
Seminiferous Tubules ◽  
Primary Group ◽  
Sprague Dawley ◽  
Intravenous Injections ◽  
Sprague Dawley Rats ◽  
Recovery Group ◽  
Ethylhexyl Phthalate

Di-(2-ethylhexyl)phthalate (DEHP) was administered to 3- to 5-day-old male Sprague-Dawley rats by daily intravenous injections of 60, 300, or 600 mg/kg/day or by daily oral gavage of 300 or 600 mg/kg/day for 21 days. Histopathological evaluation and organ weight measurements were performed on some animals after 21 days of dosing (primary group) and later on the recovery group animals that were held without further treatment until sexual maturity at approximately 90 days of age. No effects of any type were observed in animals treated intravenously with 60 mg/kg/day. Testicular changes, consisting of a partial depletion of the germinal epithelium and/or decrease in diameter of seminiferous tubules, were present in all animals of the 300- and 600-mg/kg/day groups after the 21-day dosing period. Testes weight decreased and liver weight increased in these animals. Testes changes were dose-related and generally more severe among animals dosed orally versus intravenously. In the recovery animals, a residual DEHP-induced decrease in seminiferous tubule diameter was present in the testis of several animals dosed orally at 300 and 600 mg/kg/day, but not in animals dosed intravenously. There was no germinal cell depletion or Sertoli cell alteration observed in any dose group at any time. Notably, no effects on sperm count, sperm morphology, or sperm motility were observed at 90 days of age in any of the groups.

Effect of oral administration of carbofuran on male reproductive system of rat

1995 ◽  
Vol 14 (11) ◽  
pp. 889-894 ◽  
Author(s):  
N. Pant ◽  
AK Prasad ◽  
SC Srivastava ◽  
R. Shankar ◽  
SP Srivastava
Keyword(s):  
Body Weight ◽  
Sperm Count ◽  
Reproductive Toxicity ◽  
Giant Cells ◽  
Toxicity Assessment ◽  
Male Rats ◽  
Ventral Prostate ◽  
Seminiferous Tubules ◽  
Effect Level ◽  
Dose Dependent Decrease

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.

INVESTIGATION OF THE EFFECT OF BLACK SEED OIL ON DIABETES-INDUCED - TESTICULAR DAMAGE: A HISTOPATHOLOGICAL STUDY

2021 ◽  
pp. 29-31
Author(s):  
Seval Kaya ◽  
Yusuf Nergiz ◽  
Firat Asir
Keyword(s):  
Tissue Damage ◽  
Seed Oil ◽  
Histopathological Examination ◽  
Male Rats ◽  
Seminiferous Tubules ◽  
Control Group ◽  
Histopathological Study ◽  
Diabetes Group ◽  
Black Seed ◽  
Black Seed Oil

In this study, it was aimed to investigate the protective effect of black seed oil against testicular tissue damage in diabetic rats. A total of 18 male rats were divided into 3 groups, including 6 rats in each group.Groups; control (n=6), diabetes (n=6), diabetes + black seed oil (n=6). A single dose of 45 mg / kg streptozocine (STZ) was injected intraperitoneally to induce diabetes. Diabetes + Black seed oil group: For 56 days, 2.5 ml / kg of black seed oil was administered orally to rats.The rats were sacriced at the end of 56 days. Testicular tissues were taken for routine parafn tissue processing for histopathological examination. Parafn sections were stained with Hematoxylin-Eosin and PAS and examined under a light microscope. Atrophy and degeneration were observed in the seminiferous tubules of diabetic group. Histology of black seed oil group sections were similar to that of control group. A signicant difference was found between the black seed oil group and the diabetes group in terms of blood glucose values. As a result, we think that Black Seed Oil ameliorates to the tissue damage caused by diabetes and the decrease in blood sugar value.

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