Reproductive dysfunction after mercury exposure at low levels: evidence for a role of glutathione peroxidase (GPx) 1 and GPx4 in male rats

2017 ◽  
Vol 29 (9) ◽  
pp. 1803 ◽  
Author(s):  
Caroline S. Martinez ◽  
Franck M. Peçanha ◽  
Daniela S. Brum ◽  
Francielli W. Santos ◽  
Jeferson L. Franco ◽  
...  

Mercury is a ubiquitous environmental pollutant and mercury contamination and toxicity are serious hazards to human health. Some studies have shown that mercury impairs male reproductive function, but less is known about its effects following exposure at low doses and the possible mechanisms underlying its toxicity. Herein we show that exposure of rats to mercury chloride for 30 days (first dose 4.6 µg kg–1, subsequent doses 0.07 µg kg–1 day–1) resulted in mean (± s.e.m.) blood mercury concentrations of 6.8 ± 0.3 ng mL–1, similar to that found in human blood after occupational exposure or released from removal of amalgam fillings. Even at these low concentrations, mercury was deposited in reproductive organs (testis, epididymis and prostate), impaired sperm membrane integrity, reduced the number of mature spermatozoa and, in the testes, promoted disorganisation, empty spaces and loss of germinal epithelium. Mercury increased levels of reactive oxygen species and the expression of glutathione peroxidase (GPx) 1 and GPx4. These results suggest that the toxic effects of mercury on the male reproductive system are due to its accumulation in reproductive organs and that the glutathione system is its potential target. The data also suggest, for the first time, a possible role of the selenoproteins GPx1 and GPx4 in the reproductive toxicity of mercury chloride.

Author(s):  
Asmaa ELnamaky ◽  
Amal Halawa ◽  
Mamdouh Abouelmaged

he present work was designed to investigate the reproductive toxicity induced by oral administration of chlorpyrifos (CPF), cypermethrin (CYP) and their combination in adult male albino rats. Forty mature male albino rats were separated into four groups (10 each), the first group was used as control, while second, third and fourth groups received orally 1/20 LD50 of CPF (10 mg/kg b.wt), 1/20 LD50 of CYP (17.22 mg/kg b.wt) and 1/40 LD50 of CPF plus 1/40 LD50 of CYP (5 mg/kg b.wt CPF plus 8.61 mg/kg b.wt CYP) respectively for 26 days. The results revealed that exposure to CPF and/or CYP induced a significant decrease in the reproductive organs weight. Moreover, a significant decrease in spermatic picture (sperm cell concentration and viability) was observed with high percent of sperm abnormalities. Serum levels of testosterone and pituitary gonadotropins (FSH and LH) have been declined significantly in all treated groups. Significant elevations were observed in malondialdehyde and nitric oxide concentrations, while antioxidant enzymes superoxide dismutase and glutathione-S-transferase activities were decreased significantly as a result of induced oxidative stress. A significant drop in prostatic acid phosphatase activity was observed. Additionally, the results showed some histopathological alterations in the reproductive organs as well as neurological lesions in brain and pituitary glands. In conclusion, CPF and CYP induce deleterious effects on reproductive efficiency of male rats which reflect more obvious impacts when both combined


Antioxidants ◽  
2019 ◽  
Vol 8 (8) ◽  
pp. 268 ◽  
Author(s):  
Izhar Hyder Qazi ◽  
Christiana Angel ◽  
Haoxuan Yang ◽  
Evangelos Zoidis ◽  
Bo Pan ◽  
...  

Selenium (Se) is an important trace mineral having many essential roles at the cellular and organismal levels in animal and human health. The biological effects of Se are mainly carried out by selenoproteins (encoded by 25 genes in humans and 24 in mice). As an essential component of selenoproteins, Se performs structural and enzymic roles; in the latter context it is well known for its catalytic and antioxidative functions. Studies involving different animal models have added great value to our understanding regarding the potential implications of Se and selenoproteins in mammalian fertility and reproduction. In this review, we highlight the implications of selenoproteins in male fertility and reproduction followed by the characteristic biological functions of Se and selenoproteins associated with overall male reproductive function. It is evident from observations of past studies (both animal and human) that Se is essentially required for spermatogenesis and male fertility, presumably because of its vital role in modulation of antioxidant defense mechanisms and other essential biological pathways and redox sensitive transcription factors. However, bearing in mind the evidences from mainstream literature, it is also advisable to perform more studies focusing on the elucidation of additional roles played by the peculiar and canonical selenoproteins i.e., glutathione peroxidase 4 (GPX4) and selenoprotein P (SELENOP) in the male reproductive functions. Nevertheless, search for the elucidation of additional putative mechanisms potentially modulated by other biologically relevant selenoproteins should also be included in the scope of future studies. However, as for the implication of Se in fertility and reproduction in men, though a few clinical trials explore the effects of Se supplementation on male fertility, due to inconsistencies in the recruitment of subjects and heterogeneity of designs, the comparison of such studies is still complicated and less clear. Therefore, further research focused on the roles of Se and selenoproteins is awaited for validating the evidences at hand and outlining any therapeutic schemes intended for improving male fertility. As such, new dimensions could be added to the subject of male fertility and Se supplementation.


2012 ◽  
Vol 62 (1) ◽  
pp. 43-49 ◽  
Author(s):  
Karin Viana Weissheimer ◽  
Celso Rodrigues Franci ◽  
Aldo Bolten Lucion ◽  
Gilberto Luiz Sanvitto

2021 ◽  
Vol 54 (1) ◽  
pp. 52-61
Author(s):  
NR Shepelskaya ◽  
YaV Kolyanchuk

Aim. Studying the effect of generic pesticides cyproconazole (98 %) and two samples of epoxiconazole (epoxiconazole 1 — 95,75 % and epoxiconazole 2 — 98,7 %) on the reproductive system of male and female Wistar Han rats at the level of the organism when exposed during gametogenesis, identification and characterization of their hazard, as well as assessment of the risk of reproductive toxicity of these compounds. Materials and Methods. The test samples were administered daily (5 days a week) by oral gavage at doses of 0.2 and 2.0 mg/kg for cyproconazole and 0.5 and 2.0 mg/kg for epoxiconazoles during 11 weeks for males, and 10 weeks for females. Also, there were kept intact males and females, intended for crossover mating with experimental animals. After the end of the exposure, functional indicators of the state of the gonads and the ability of animals to reproduce offspring were studied. The duration and the frequency of each stage of the estrous cycle in female rats and the number of motile sperm, the total amount of sperm and the number of abnormal forms of germ cells of the male rats were studied. The reproductive function state in females was evaluated on day 20th of pregnancy. Thereby the number of corpora lutea in the ovaries, number of alive, dead and resorbed foetuses and embryos, the foetus weight, total weight of litters were registered. The studies were carried out in accordance with the recommendations of the Bioethics Commission and the Centre’s standard operating procedures, developed in accordance with the recommendations and requirements of Good Laboratory Practice (GLP). Conclusions. Test substances at a maximum dose of 2.0 mg/kg of body weight have reproductive toxicity and endocrine-disruptive effect, exerting a significant antiandrogenic effect on males and antiestrogenic effect on female rats. No-observed-adverse-effect-level (NOАEL) for gonadal and reproductive toxicity for male and female Wistar Han rats were established. They are 0.2 mg/kg body weight for cyproconazole and 0.5 mg/kg body weight for epoxiconazole. Key Words: azole fungicides, cyproconazole, epoxiconazole, reproductive toxicity, antiandrogenic and antiestrogenic effects, Wistar Han rats.


Development ◽  
2000 ◽  
Vol 127 (1) ◽  
pp. 143-153 ◽  
Author(s):  
D. Thepot ◽  
J.B. Weitzman ◽  
J. Barra ◽  
D. Segretain ◽  
M.G. Stinnakre ◽  
...  

JunD is one of three mammalian Jun proteins that contribute to the AP-1 transcription factor complex. Distinct regulation and functions have been proposed for each Jun member, but less is known about the biological functions of each of these proteins in vivo. To investigate the role of JunD, we have inactivated the murine gene by replacement with a bacterial lacZ reporter gene. Embryonic JunD expression was initially detected in the developing heart and cardiovascular system. Subsequent broadening phases of JunD expression were observed during embryonic development and expression in the adult was widespread in many tissues and cell lineages. Mutant animals lack JunD mRNA and protein and showed no evidence of upregulation of c-Jun and JunB mRNA levels. In contrast to the other two Jun members, homozygous JunD−/− mutant animals were viable and appeared healthy. However, homozygous JunD−/− animals showed a reduced postnatal growth. Furthermore, JunD−/− males exhibited multiple age-dependent defects in reproduction, hormone imbalance and impaired spermatogenesis with abnormalities in head and flagellum sperm structures. No defects in fertility were observed in JunD−/− female animals. These results provide evidence for redundant functions for members of the Jun family during development and specific functions for JunD in male reproductive function.


2013 ◽  
Vol 110 (09) ◽  
pp. 469-475 ◽  
Author(s):  
Åke Lundwall

SummaryThe human kallikrein locus consists of KLK1, the gene of major tissue kallikrein, and 14 genes of kallikrein-related peptidases (KLKs) located in tandem on chromosome 19q13.3-13.4. In this review, based on information retrieved from the literature or extracted from genome databases, it is hypothesised that the kallikrein locus is unique to mammals. The majority of genes are highly conserved, as demonstrated by the identification of 11 KLK genes in the opossum, a metatherian species. In contrast, a sublocus, encompassing KLK1-4, has gone through major transformations that have generated new genes, which in most cases are closely related to KLK1. In the primate lineage, this process created KLK3, the gene of the prostate cancer marker, prostate-specific antigen (PSA), whereas in the murine lineage it gave rise to 13 genes unique to the mouse and nine unique to the rat. The KLK proteases are effector molecules that emerged early in mammalian evolution and their importance in skin homeostasis and male reproductive function is undisputed and there are also accumulating evidence for a role of KLK proteases in the development of the brain. It is speculated that the KLK gene family arose as part of the process that generated distinguishing mammalian features, like skin with hair and sweat glands, and specialised anatomical attributes of the brain and the reproductive tract.


2011 ◽  
Vol 282-283 ◽  
pp. 195-200
Author(s):  
Yu Bin Ji ◽  
Jing Chao Sun ◽  
Lang Lang

Solanine is one of chemicalcomponents in the tuber and the sprout of the potato which is toxic to human. Some studies on the toxicity of solanine on humans and animals have been reported, little is known about the mechanism of its testicular toxicity. In present study, the toxicity of solanine on male reproductive function was investigated in adult male Kunming mice. Compared with the control group, there was an obvious pathological change in testis, and the expression levels of 3β-HSD and vimentin decreased when the test concentration of solanine was at 21 mg/kg/day. Meanwhile, there was a significant dose- and duration-dependent reduction in the testicular weight and organ coefficient. However, no changes have been detected about the level of testosterone and there was a dramatic increase in the expression of LH in Leydig cells. Results of this study suggested that solanine leaded to male reproductive toxicity influencing the functions of Sertoli cells and Leydig cells.


2011 ◽  
Vol 101 (3) ◽  
pp. 175-181 ◽  
Author(s):  
Reda H. ElMazoudy ◽  
Azza A. Attia ◽  
Nahla S. El-Shenawy

2021 ◽  
Vol 12 (4) ◽  
pp. 2308-2315
Author(s):  
Rachid Mosbah ◽  
Aziez Chettoum ◽  
Alberto Mantovani

Selective serotonin reuptake inhibitors (SSRI) are a class of molecules used in treating depression, anxiety, and mood disorders. Paroxetine (PRT) is one of the most prescribed antidepressants, which has attracted great attention regarding its side effects in recent years.  This study was planned to assess the adverse effects of paroxetine on the biochemical parameters and reproductive system. Fourteen male Wistar rats were randomly allocated into two groups (7 rats for each): control and treated with paroxetine at a dose of 5mg/kg.bw for two weeks. At the end of the experiment, blood was collected from the retro-orbital plexus for measuring the biochemical parameters, whereas the reproductive organs were removed for measuring semen quality and the histological investigations. Results showed that paroxetine induced significant changes in some biochemical parameters and alteration of semen quality, including sperm count, spermatids number and sperm viability, motility and abnormalities. The histopathological examinations of testis and epididymis revealed an alteration of spermatogenesis, cellular disorganization and vacuolization, enlargement of interstitial space, shrinkage and degenerative changes in the epithelium of seminiferous and epididymal tubules with few to nil numbers of spermatozoa in their lumen. In conclusion, paroxetine treatment caused changes in some biochemical parameters and sperm profiles as well as histopathologic effects of reproductive organs.


2018 ◽  
Vol 38 (4) ◽  
pp. 398-408 ◽  
Author(s):  
AA Khalaf ◽  
WMS Ahmed ◽  
WA Moselhy ◽  
BR Abdel-Halim ◽  
MA Ibrahim

Bisphenol A (BPA) is a widespread compound associated with the manufacture of many consumer products. The BPA-induced reproductive toxicity was reported to be mainly attributed to oxidative stress. However, the role of antioxidants usage to decrease the injurious effects of BPA, on male reproductive functions, remains to unveil. The present research is established to evaluate the role of selenium (Se) and its nano form (NSe) as protective agents to alleviate BPA-induced testicular toxicity. Ninety mature albino male rats were assigned into six equal groups: negative control; orally BPA 150 mg/kg; Se 3 mg/kg; NSe 2 mg/kg; both BPA 150 mg/kg and Se 3 mg/kg; and BPA 150 mg/kg + NSe 2 mg/kg. The experiment lasted for 70 consecutive days, and then serum was collected for estimation of prostatic acid phosphatase. Testicular tissues were subjected to measurement of antioxidant status, lipid peroxidation, DNA damage, and expression of some apoptotic genes. Our results reported that BPA-induced marked testicular damage evidenced by significant elevations in serum prostatic acid phosphatase activity, malondialdehyde levels, a decrease in testicular catalase activity and reduced glutathione level. Moreover, marked DNA internucleosomal fragmentation pattern as well as upregulation of cyclooxygenase-2 and estrogen receptor-2 NSe genes were detected. Coadministration of Se and NSe attenuated the reproductive toxicity induced by BPA via improvement of the antioxidant activity, genetic changes, and restoration of testicular tissue nearly as control one. These results indicated that both Se and NSe forms could be used as reproductive protective agents against the detrimental effect induced by BPA. However, the NSe surpassed the selenium in modulating the DNA laddering, and the studied gene expression levels, and offered a potent reproductive protection.


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