Low Doses of Glyphosate/Roundup Alter Blood–Testis Barrier Integrity in Juvenile Rats

It has been postulated that glyphosate (G) or its commercial formulation Roundup (R) might lead to male fertility impairment. In this study, we investigated the possible effects of G or R treatment of juvenile male rats on blood-testis barrier function and on adult male sperm production. Pups were randomly assigned to the following groups: control group (C), receiving water; G2 and G50 groups, receiving 2 and 50 mg/kg/day G respectively; and R2 and R50 groups receiving 2 and 50 mg/kg/day R respectively. Treatments were performed orally from postnatal day (PND) 14 to 30, period of life that is essential to complete a functional blood-testis barrier. Evaluation was done on PND 31. No differences in body and testis weight were observed between groups. Testis histological analysis showed disorganized seminiferous epithelium, with apparent low cellular adhesion in treated animals. Blood-testis barrier permeability to a biotin tracer was examined. A significant increase in permeable tubules was observed in treated groups. To evaluate possible mechanisms that could explain the effects on blood-testis barrier permeability, intratesticular testosterone levels, androgen receptor expression, thiobarbituric acid reactive substances (TBARS) and the expression of intercellular junction proteins (claudin11, occludin, ZO-1, connexin43, 46, and 50 which are components of the blood-testis barrier) were examined. No modifications in the above-mentioned parameters were detected. To evaluate whether juvenile exposure to G and R could have consequences during adulthood, a set of animals of the R50 group was allowed to grow up until PND 90. Histological analysis showed that control and R50 groups had normal cellular associations and complete spermatogenesis. Also, blood-testis barrier function was recovered and testicular weight, daily sperm production, and epididymal sperm motility and morphology did not seem to be modified by juvenile treatment. In conclusion, the results presented herein show that continuous exposure to low doses of G or R alters blood-testis barrier permeability in juvenile rats. However, considering that adult animals treated during the juvenile stage showed no differences in daily sperm production compared with control animals, it is feasible to think that blood-testis barrier impairment is a reversible phenomenon. More studies are needed to determine possible damage in the reproductive function of human juvenile populations exposed to low doses of G or R.

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Prolonged deleterious effects of neonatal handling on reproductive parameters of pubertal male rats

Reproduction Fertility and Development ◽

10.1071/rd04076 ◽

2006 ◽

Vol 18 (4) ◽

pp. 497 ◽

Cited By ~ 16

Author(s):

Renata Mazaro ◽

Teresa Lúcia Lamano-Carvalho

Keyword(s):

Sertoli Cells ◽

Seminiferous Tubule ◽

Male Rats ◽

Germinal Epithelium ◽

Reproductive Parameters ◽

Sperm Production ◽

Neonatal Handling ◽

Epithelium Thickness ◽

Cauda Epididymidis ◽

Daily Sperm Production

The purpose of the present study was to investigate the long-lasting effects of neonatal handling on reproductive parameters of male rats. Neonatal handling (pups separated from their mothers, kept isolated at environmental temperature for 20 min and submitted to 1 min of tactile stimulation) was applied from post partum Days 1 to 14 (a stress-hyporesponsive period, SHRP) and the animals were killed at puberty (61 days of age). The number of mature spermatids and the daily sperm production were estimated in homogenates from the right testes and cauda epididymidis. Histometric parameters (diameter of seminiferous tubule, germinal epithelium thickness and number of Sertoli cells) were evaluated in paraplast sections of the left testes. The association of the slightly aversive stimuli applied during the SHRP proved to have lasting deleterious effects on male reproduction, causing lower testicular weight and reduced values of seminiferous tubule diameter and germinal epithelium thickness at puberty, which resulted in a 25% reduction in the daily sperm production and in the number of mature spermatids. Similarly, the number of Sertoli cells per tubular cross section was 20% smaller and the weight and number of spermatozoa were reduced more than 40% in the cauda epididymidis of animals handled.

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Ameliorative effect of quercetin against arsenic-induced sperm DNA damage and daily sperm production in adult male rats

Drug and Chemical Toxicology ◽

10.3109/01480545.2015.1101772 ◽

2015 ◽

Vol 39 (3) ◽

pp. 290-296 ◽

Cited By ~ 5

Author(s):

Sarwat Jahan ◽

Saima Rehman ◽

Hizb Ullah ◽

Asma Munawar ◽

Qurat Ul Ain ◽

...

Keyword(s):

Dna Damage ◽

Adult Male ◽

Male Rats ◽

Sperm Production ◽

Sperm Dna Damage ◽

Sperm Dna ◽

Ameliorative Effect ◽

Daily Sperm Production

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Nobiletin ameliorates nonylphenol-induced testicular damage by improving biochemical, steroidogenic, hormonal, spermatogenic, apoptotic and histological profile

Human & Experimental Toxicology ◽

10.1177/0960327120950007 ◽

2020 ◽

pp. 096032712095000

Author(s):

Muhammad Umar Ijaz ◽

Arfa Tahir ◽

Abdul Samad ◽

Haseeb Anwar

Keyword(s):

Oxidative Stress ◽

Caspase 3 ◽

Sperm Count ◽

Thiobarbituric Acid ◽

Male Rats ◽

Plasma Testosterone ◽

Sperm Production ◽

Thiobarbituric Acid Reactive Substances ◽

Apoptotic Protein ◽

Daily Sperm Production

Nonylphenol (NP) is an environmental contaminant, which adversely affects the male fertility due to endocrine disruption and generation of oxidative stress. The current research was planned to assess the effects of nobiletin (NOB), a polymethoxyflavone, on NP-induced testicular damages. Twenty-four male rats were divided into 4 groups: control (0.1% DMSO), NP group (50 mg/kg), NP+NOB group (50 mg/kg + 25 mg/kg), and NOB group (25 mg/kg). Our results revealed that NP brought down the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and glutathione reductase (GSR), while elevated the level of thiobarbituric acid reactive substances (TBARS). Additionally, NP decreased the level of follicle-stimulating hormone (FSH), luteinizing hormone (LH), plasma testosterone, daily sperm production (DSP), epididymal sperm count, viability, motility, gene expression of testicular steroidogenic enzymes (StAR, 3β-HSD and 17β-HSD) and anti-apoptotic protein (Bcl-2), as well as number of spermatogenic cells belonging to various stages. Whereas, sperm (head, mid-piece/neck and tail) abnormalities, expression of apoptotic proteins (Bax and caspase-3), and histopathological damages were increased. However, NOB remarkably reversed all the damages caused by NP. Therefore, it is deduced that NOB could be used as a potential therapeutic to counter the NP-prompted oxidative stress and apoptotic damages in testes.

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Reproductive effects of endosulfan on male offspring of rats exposed during pregnancy and lactation

Human & Experimental Toxicology ◽

10.1191/096032799678845124 ◽

1999 ◽

Vol 18 (9) ◽

pp. 583-589 ◽

Cited By ~ 38

Author(s):

P R Dalsenter ◽

E Dallegrave ◽

J Rb Mello ◽

A Langeloh ◽

R T Oliveira ◽

...

Keyword(s):

Male Offspring ◽

Male Rats ◽

Male Rat ◽

Seminiferous Tubules ◽

Sperm Production ◽

Rat Offspring ◽

Stage Of Development ◽

Reproductive Effects ◽

Pregnancy And Lactation ◽

Daily Sperm Production

1 The reproductive effects of endosulfan on the male offspring of rats were examined. Dams were treated orally with 0, 1.5 or 3.0 mg endosulfan/kg from day 15 of pregnancy to postnatal day (PND) 21 of lactation. The male offspring rats were investigated at PND 65 or 140, corresponding to the pubertal and adulthood stage of development. 2 The dose of 3.0 mg endosulfan/kg induced a decrease in maternal body weight during pregnancy, but litter size and mean birth weight were not affected. Similarly, the age at testis descent and preputial separation was not affected on the male offspring. 3 The daily sperm production (6106) was permanently decreased in the highest dose group when investigated at puberty and at adulthood. At the lowest dose, however, the daily sperm production was significantly reduced only at puberty. 4 Histologically, the percentage of seminiferous tubules showing complete spermatogenesis was significantly decreased at puberty. This finding may explain the decrease in daily sperm production observed in the endosulfan-exposed male rats. 5 The results of this study show that low doses of endosulfan have no apparent effect on developmental landmarks or on the weight of reproductive and accessory sex organ. Daily sperm production was the most susceptible endpoint in the male offspring exposed to endosulfan during pregnancy and lactation. To further understand the reproductive effects of endosulfan on male rat offspring, additional reproductive and toxicokinetic studies should be carried out to determine the extent of endosulfan exposure in male rat offspring in utero and during lactation.

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Chronic exposure of bisphenol S (BPS) affect hypothalamic-pituitary-testicular activities in adult male rats: possible in estrogenic mode of action

Environmental Health and Preventive Medicine ◽

10.1186/s12199-021-00954-0 ◽

2021 ◽

Vol 26 (1) ◽

Author(s):

Hizb Ullah ◽

Faizan Ullah ◽

Owais Rehman ◽

Sarwat Jahan ◽

Tayyaba Afsar ◽

...

Keyword(s):

Oxidative Stress ◽

Chronic Exposure ◽

Structural Changes ◽

Gonadosomatic Index ◽

Male Rats ◽

Plasma Testosterone ◽

Seminiferous Tubules ◽

Sperm Production ◽

Bisphenol S ◽

Daily Sperm Production

Abstract Background The industrial revolution has resulted in increased synthesis and the introduction of a variety of compounds into the environment and their potentially hazardous effects have been observed in the biota. The present study was aimed to evaluate the potential endocrine-disrupting effects of chronic exposure to the low concentrations of bisphenol S (BPS) in male rats. Methods Weaning male Sprague-Dawley rats (22 days old) were either exposed to water containing 0.1% ethanol for control or different concentrations of BPS (0.5, 5, and 50 μg/L) in drinking water for 48 weeks in the chronic exposure study. After completion of the experimental period, animals were dissected and different parameters (hormone concentrations, histology of testis and epididymis, oxidative stress and level of antioxidant enzymes in the testis, daily sperm production (DSP), and sperm parameters) were determined. Results Results of the present study showed a significant alteration in the gonadosomatic index (GSI) and relative reproductive organ weights. Oxidative stress in the testis was significantly elevated while sperm motility, daily sperm production, and the number of sperm in epididymis were reduced. Plasma testosterone, luteinizing hormone (LH), and follicle-stimulating hormone (FSH) concentrations were reduced and estradiol levels were high in the 50 μg/L-exposed group. Histological observations involved a significant reduction in the epithelial height of the testis along with disrupted spermatogenesis, an empty lumen of the seminiferous tubules, and the caput region of the epididymis. Conclusion These results suggest that exposure to 5 and 50 μg/L of BPS for the chronic duration started from an early age can induce structural changes in testicular tissue architecture and endocrine alterations in the male reproductive system which may lead to infertility in males.

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Potentiation of bromotrichloromethane hepatotoxicity in male rats exposed to 10 ppm dietary chlordecone: Electron Microscopic and biochemical study

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100158972 ◽

1990 ◽

Vol 48 (3) ◽

pp. 284-285

Author(s):

O. M. Faroon ◽

R. W. Henry ◽

M. G. Soni ◽

H. M. Mehendale

Keyword(s):

Free Radical ◽

Biochemical Study ◽

Prior Exposure ◽

Male Rats ◽

Cellular Injury ◽

Low Doses ◽

Mixed Function Oxidase ◽

Electron Microscopic ◽

Potent Inducer ◽

Cellular Energy

Previous work has shown that mirex undergoes photolytic dechlorination to chlordecone (CD) (KeponeR) in the environment. Much work has shown that prior exposure to nontoxic levels of CD causes potentiation of hepatotoxicity and lethality of CCl4, BrCCl3 and other halomethane compounds. Potentiation of bromotrichloromethane hepatotoxicity has been associated with compounds that stimulate the activity of hepatic mixed-function oxidase (MFO). An increase in the metabolism of halomethane by the MFO to a free radical initiates peroxidative decomposition of membranal lipids ending in massive cellular injury. However, not all MFO inducers potentiate BrCCl3 hepatotoxicity. Potentiation by much larger doses of phenobarbital is minimal and th at by a more potent inducer of MFO, mirex, is negligible at low doses. We suggest that the CD and bromotrichloromethane interaction results in a depletion of cellular energy and thereby reducing the cellular ability to undergo mitosis.

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Bacillus cereus Induces Permeability of an In Vitro Blood-Retina Barrier

Infection and Immunity ◽

10.1128/iai.01330-07 ◽

2008 ◽

Vol 76 (4) ◽

pp. 1358-1367 ◽

Cited By ~ 16

Author(s):

A. L. Moyer ◽

R. T. Ramadan ◽

J. Thurman ◽

A. Burroughs ◽

M. C. Callegan

Keyword(s):

Quorum Sensing ◽

Bacillus Cereus ◽

Barrier Function ◽

Pigment Epithelium ◽

Retinal Pigment ◽

Toxin Production ◽

Global Regulator ◽

Barrier Permeability ◽

Cell Monolayers

ABSTRACT Most Bacillus cereus toxin production is controlled by the quorum-sensing-dependent, pleiotropic global regulator plcR, which contributes to the organism's virulence in the eye. The purpose of this study was to analyze the effects of B. cereus infection and plcR-regulated toxins on the barrier function of retinal pigment epithelium (RPE) cells, the primary cells of the blood-retina barrier. Human ARPE-19 cells were apically inoculated with wild-type or quorum-sensing-deficient B. cereus, and cytotoxicity was analyzed. plcR-regulated toxins were not required for B. cereus-induced RPE cytotoxicity, but these toxins did increase the rate of cell death, primarily by necrosis. B. cereus infection of polarized RPE cell monolayers resulted in increased barrier permeability, independent of plcR-regulated toxins. Loss of both occludin and ZO-1 expression occurred by 8 h postinfection, but alterations in tight junctions appeared to precede cytotoxicity. Of the several proinflammatory cytokines analyzed, only interleukin-6 was produced in response to B. cereus infection. These results demonstrate the deleterious effects of B. cereus infection on RPE barrier function and suggest that plcR-regulated toxins may not contribute significantly to RPE barrier permeability during infection.

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