Toxicity In Male Reproductive System Research Articles

Insight into the mechanism of aspartame-induced toxicity in male reproductive system following long-term consumption in mice model.

Aspartame is one of the most common consumed artificial sweeteners utilized in many food products and beverages. It has been indicated that long-term consumption of aspartame leads to reproductive toxicity but its mechanism is not well-clear. In this study we investigated mechanism of aspartame-induced reproductive toxicity in male mice. For this purpose, 36 NMRI mature male mice received three doses of 40, 80, and 160 mg/kg body weight of aspartame, respectively per day by gavage for 90 days and also a control group was considered which received 0.5 mL of normal saline as the same route. The results revealed that long-term administration of aspartame at high doses significantly (P < .05) reduced gonadosomatic index, serum concentration of pituitary-testicular axis hormones (FSH, LH, and testosterone). It also decreased sperm parameters and total antioxidant capacity, antioxidant enzyme activities (superoxide dismutase, catalase, and glutathione peroxidase), while it caused increase in nitric oxide and malondialdehyde levels in testis tissue and sperm samples. Also, it decreased attenuated testicular histomorphometric indices (tubular differentiation index, spermiogenesis index, and repopulation index), and steroidogenic foci, while increased mRNA damages and apoptosis rate, downregulated antiapoptotic (Bcl-2) and upregulated proapoptotic (P53, BAX, and caspase-3) mediators respectively in testis. These findings indicated that consumption of aspartame for a long period results in male reproductive toxicity by decrease in serum concentration of pituitary-testis axis hormones and induction of oxidative stress and apoptosis in testis.

Defensive Effects of Breberine against Cypermethrin Induced Male Reproductive System Toxicity in Rabbits

Current research has determined the protective role of Berberine (BRB) in the reproductive toxicity induced by cypermethrin (CYP) in male rabbits, Twenty adult New Zealand white rabbits were randomized into four main groups: group I (control group ) received (1 ml / kg b.w saline orally), group II received (CYP64mg / kg b. w./orally); group III (received BRB 50 mg / kg b. w./plus CYP64mg / kg b.w orally); and group IV (received BRB 100 mg / kg b. w plus CYP64mg.kg b. w orally) received all oral gavage therapies for 21 consecutive days. On the (22) day of the experiment, all the rabbits were scarified, and then samples were taken of the blood, testis and caudal epididymis. CYP exposures were found to have substantial adverse effects on the reproductive system of adult male rabbits as a result of decreased testicular and epididymal weight, a significant decrease (p<0.05) in serum testosterone (T) and increase significantly in follicle stimulating hormone ( FSH), luteinizing hormone ( LH), Changes and histopathological ones. BRB has a substantial improvement in T, FSH and LH (p < 0.01) and enhances tissue morphology in BRB (50 mg/kg), while BRB (100 mg/kg) has more reproductive system curative ability. These findings indicate that CYP-induced reproductive system toxicity in rabbits can be covered by BRB (100 mg/kg) antioxidant impact. How to Cite this Article Pubmed Style Murad HM, Abdulameer SA, Aljuboory DSA, Neamah DA, Maktouf AH. Effects of Breberine against Cypermethrin Induced Male Reproductive System Toxicity in SRP. 2020; 11(9): 841-846. doi:10.31838/srp.2020.9.120 Web Style Murad HM, Abdulameer SA, Aljuboory DSA, Neamah DA, Maktouf AH. Effects of Breberine against Cypermethrin Induced Male Reproductive System Toxicity in http://www.sysrevpharm.org/?mno=20544 [Access: March 31, 2021]. doi:10.31838/srp.2020.9.120 AMA (American Medical Association) Style Murad HM, Abdulameer SA, Aljuboory DSA, Neamah DA, Maktouf AH. Effects of Breberine against Cypermethrin Induced Male Reproductive System Toxicity in SRP. 2020; 11(9): 841-846. doi:10.31838/srp.2020.9.120 Vancouver/ICMJE Style Murad HM, Abdulameer SA, Aljuboory DSA, Neamah DA, Maktouf AH. Effects of Breberine against Cypermethrin Induced Male Reproductive System Toxicity in SRP. (2020), [cited March 31, 2021]; 11(9): 841-846. doi:10.31838/srp.2020.9.120 Harvard Style Murad, H. M., Abdulameer, . S. A., Aljuboory, . D. S. A., Neamah, . D. A. & Maktouf, . A. H. (2020) Effects of Breberine against Cypermethrin Induced Male Reproductive System Toxicity in SRP, 11 (9), 841-846. doi:10.31838/srp.2020.9.120 Turabian Style Murad, Hawraa M., Shurooq Asaad Abdulameer, Dhuha Salman Asker Aljuboory, Dheyaa A. Neamah, and Ali Hamza Maktouf. 2020. Effects of Breberine against Cypermethrin Induced Male Reproductive System Toxicity in Systematic Reviews in Pharmacy, 11 (9), 841-846. doi:10.31838/srp.2020.9.120 Chicago Style Murad, Hawraa M., Shurooq Asaad Abdulameer, Dhuha Salman Asker Aljuboory, Dheyaa A. Neamah, and Ali Hamza Maktouf. Defensive Effects of Breberine against Cypermethrin Induced Male Reproductive System Toxicity in Rabbits. Systematic Reviews in Pharmacy 11 (2020), 841-846. doi:10.31838/srp.2020.9.120 MLA (The Modern Language Association) Style Murad, Hawraa M., Shurooq Asaad Abdulameer, Dhuha Salman Asker Aljuboory, Dheyaa A. Neamah, and Ali Hamza Maktouf. Defensive Effects of Breberine against Cypermethrin Induced Male Reproductive System Toxicity in Rabbits. Systematic Reviews in Pharmacy 11.9 (2020), 841-846. Print. doi:10.31838/srp.2020.9.120 APA (American Psychological Association) Style Murad, H. M., Abdulameer, . S. A., Aljuboory, . D. S. A., Neamah, . D. A. & Maktouf, . A. H. (2020) Effects of Breberine against Cypermethrin Induced Male Reproductive System Toxicity in Systematic Reviews in Pharmacy, 11 (9), 841-846. doi:10.31838/srp.2020.9.120

Review on arsenic-induced toxicity in male reproductive system and its amelioration.

Arsenic is an environmental toxicant which causes mutagenic, teratogenic and carcinogenic defects. It is used as herbicide, fungicide and rodenticide and results in contamination of air, soil and water. Arsenic is also produced through burning of coal industries. The sludge of factories contaminates the fodder and drinking source of water of human and livestock. Arsenic binds thiol groups in tissue proteins and impairs the function of the proteins. This metal affects the mitochondrial enzymes and interrupts the production of energy. Oxidative stress and the generation of reactive oxygen species could also be a consequence of arsenic exposure. High arsenic level may suppress the sensitivity of gonadotroph cells to GnRH as well as gonadotropin secretion by elevating plasma levels of glucocorticoids. These ultimately lead to the development of gonad toxicity in animals and cause the reduction in sperm number, sperm viability and motility. Massive degeneration of germ cells and alterations in the level of LH, FSH and testosterone are also reported. The objective of this review was to find out the effects of arsenic-induced toxicity on male reproductive system in animals and its amelioration.

Mitigation of paracetamol-induced reproductive damage by chrysin in male rats via reducing oxidative stress.

Paracetamol (PRC) is a nonsteroidal anti-inflammatory drug used widely as a painkiller for various diseases and as the symptomatic flu cure in several countries worldwide. PRC toxicity may occur under conditions of the overdose usage. Chrysin (CR) is a flavonoid that is naturally present in several plants, honey and propolis. The aim of this study was to investigate the effects of CR (at the doses of 25mgkg-1 and 50mgkg-1 ) pre-treatment over seven consecutive days against PRC-induced reproductive toxicity in male rats. Our results showed that PRC toxicity decreased the sperm motility, and increased dead sperm rate, abnormal sperm cell rate, apoptosis and MDA levels in testicular tissues. Pre-treatment with CR at the dose of 25 and 50mgkg-1 for 7days mitigated side effects of acute PRC toxicity in male reproductive system proportionally in a dose-dependent manner. This possible protection mechanism might be dependent on the antioxidant activity of CR. In conclusion, pre-treatment with CR at the dose of 25 and 50mgkg-1 for 7days can be the beneficial against PRC-induced reproductive toxicity proportionally in a dose-dependent manner.

Indium acetate toxicity in male reproductive system in rats.

Indium, a rare earth metal characterized by high plasticity, corrosion resistance, and a low melting point, is widely used in the electronics industry, but has been reported to be an environmental pollutant and a health hazard. We designed a study to investigate the effects of subacute exposure of indium compounds on male reproductive function. Twelve-week old male Sprague-Dawley rats were randomly divided into test and control groups, and received weekly intraperitoneal injections of indium acetate (1.5 mg/kg body weight) and normal saline, respectively, for 8 weeks. Serum indium levels, cauda epididymal sperm count, motility, morphology, chromatin DNA structure, mitochondrial membrane potential, oxidative stress, and testis DNA content were investigated. The indium acetate-treated group showed significant reproductive toxicity, as well as an increased percentage of sperm morphology abnormality, chromatin integrity damage, and superoxide anion generation. Furthermore, positive correlations among sperm morphology abnormalities, chromatin DNA damage, and superoxide anion generation were also noted. The results of this study demonstrated the toxic effect of subacute low-dose indium exposure during the period of sexual maturation on male reproductive function in adulthood, through an increase in oxidative stress and sperm chromatin DNA damage during spermiogenesis, in a rodent model.

Male reproductive system toxicity and sexual dysfunction caused by drugs

Objective Domestic and foreign literatures about male reproductive svstem toxicity and sexual dysfunction caused by drugs were analyzed to describe the damage to male reproductive system,guide them to scientificly and rationally use drug,and av oid the damage to reproductive svstem caused by drugs.Methods Cases with male reproductive system toxicity and sexual dvsfunction caused by drugs and domesticly and foreignly reported from January.2001 to December,2012 were statistically analyzed.Results 30.8％ cases with male reproductive system toxicity and sexual dysfunction were caused by cardiovascular system drugs,17.3％ by anti-infection drugs,and 18.8％ by anti-mental-disorder drugs.Most the adverse reactions occurred within one month after the medication.Conclusion Male reproductive system toxicity and sexual dysfunction are mainly caused by cardiovascular system,anti-infection,and anti-mental-disorder drugs. Key words: Drugs; Male reproductive system toxicity; Sexual dysfunction; Adverse reaction

β‐benzene hexachloride induces apoptosis of rat sertoli cells through generation of reactive oxygen species and activation of JNKs and FasL

β-benzene hexachloride (β-BHC), the major metabolite of benzene-hexachloride (BHC), is a weak estrogen-like chemical. It is a known persistent organic pollutant and male reproductive toxicant. However, the mechanism by which β-BHC exposure causes male reproductive toxicity remains unknown. In the present study, rat Sertoli cells were used to investigate the molecular mechanism involved in β-BHC-induced toxicity in male reproductive system. The results indicated that β-BHC exposure at over 30 μM showed the induction of apoptotic cell death. β-BHC could induce elevation in reactive oxygen species (ROS) generation, increase in the leakage rate of LDH and MDA level, and decrease in SOD activity. In addition, there was an increase in the cellular levels of phospho-JNKs and FasL in the β-BHC-induced apoptosis; and a significant reduction of procaspase-3 and -8 was observed over 30-μM β-BHC treatment. The translocation of NF-κB enhanced with the increase of concentration of β-BHC. Furthermore, NAC administration, a scavenger of ROS, reversed β-BHC-induced apoptosis effects via inhibition of JNKs activation, FasL expression, and NF-κB translocation. These results lead us to speculate that ROS generation may play a critical role in the initiation of β-BHC-induced apoptosis by activation of the JNKs, translocation of NF-κB, expression of FasL, and further activation of caspase cascade.

Evaluation of vitamin E and calcium effects on fluoride toxicity-induced fertility impairment

Chronic fluoride (Fl) toxicity is a serious public health problem globally where drinking water contains more than 1 ppm of Fl. Sodium fluoride (NaF) produced male reproductive system toxicity. The aim of the present study was to evaluate the amelioration of Fl toxicity-induced fertility impairment by vitamin E and calcium during the withdrawal period. The study was carried out on 70 adult male albino rats divided into five main groups: group I control; subdivided into group Ia (maintained on standard diet and water ad libitum for 60 days) and group Ib (maintained on standard diet and water ad libitum for 120 days), group II was administered NaF and subdivided into group IIa (administered NaF for 60 day and sacrificed) and group IIb (administered NaF for 60 day then maintained on standard diet and water ad libitum for a further 60 days), and treated groups III, IV, and V were administered NaF. Rats were maintained during withdrawal from NaF, on vitamin E (10 mg kg−1 day−1 for 60 days), calcium (50 mg kg−1 day−1 orally for 60 days), and both vitamin E and calcium, respectively. The duration of NaF administration was 60 days at a dose 20 mg kg−1 day−1 for all treated groups. The following parameters were determined: body and organ weights, sperm motility, sperm morphology, sperm viability, fertility test, and hormone assays: testosterone, in vitro testosterone production, luteinizing hormone, and follicular stimulating hormone. The combined administration of vitamin E and calcium during withdrawal from NaF showed significant improvement from chronic FL-induced toxicity on male reproductive organs.

P,p′‐DDE Induces Apoptosis of Rat Sertoli Cells via a FasL‐Dependent Pathway

One,1-dichloro-2,2 bis(p-chlorophenyl) ethylene (p,p′-DDE), the major metabolite of 2,2-bis(4-Chlorophenyl)-1,1,1-trichloroethane (DDT), is a known persistent organic pollutant and male reproductive toxicant. It has antiandrogenic effect. However, the mechanism by which p,p′-DDE exposure causes male reproductive toxicity remains unknown. In the present study, rat Sertoli cells were used to investigate the molecular mechanism involved in p,p′-DDE-induced toxicity in male reproductive system. The results indicated that p,p′-DDE exposure at over 30 μM showed the induction of apoptotic cell death. p,p′-DDE could induce increases in FasL mRNA and protein, which could be blocked by an antioxidant agent, N-acetyl-l-cysteine (NAC). In addition, caspase-3 and -8 were activated by p,p′-DDE treatment in these cells. The activation of NF-κB was enhanced with the increase of p,p′-DDE dose. Taken together, these results suggested that exposure to p,p′-DDE might induce apoptosis of rat Sertoli cells through a FasL-dependent pathway.

Abnormalities of Sexual Development in Male Rats with in Utero and Lactational Exposure to the Antiandrogenic Plasticizer Di(2-Ethylhexyl) Phthalate

Several members of the phthalate ester family have antiandrogenic properties, yet little is known about how exposure to these ubiquitous environmental contaminants early in development may affect sexual development. We conducted experiments to determine effects of in utero and lactational exposure to the most prevalent phthalate ester, di(2-ethylhexyl) phthalate (DEHP), on male reproductive system development and sexual behavior. Sprague-Dawley rats were dosed with corn oil or DEHP (0, 375, 750, or 1,500 mg/kg/day, per os) from gestation day 3 through postnatal day (PND) 21. Dose-related effects on male offspring included reduced anogenital distance, areola and nipple retention, undescended testes, and permanently incomplete preputial separation. Testis, epididymis, glans penis, ventral prostate, dorsolateral prostate, anterior prostate, and seminal vesicle weights were reduced at PND 21, 63, and/or 105-112. Additional dose-related effects included a high incidence of anterior prostate agenesis, a lower incidence of partial or complete ventral prostate agenesis, occasional dorsolateral prostate and seminal vesicle agenesis, reduced sperm counts, and testicular, epididymal, and penile malformations. Many DEHP-exposed males were sexually inactive in the presence of receptive control females, but sexual inactivity did not correlate with abnormal male reproductive organs. These results suggest that in utero and lactational DEHP exposure also inhibited sexually dimorphic central nervous system development. No major abnormalities were found in any of eight control litters, but DEHP caused severe male reproductive system toxicity in five of eight litters at 375 mg/kg/day, seven of eight litters at 750 mg/kg/day, and five of five litters at 1,500 mg/kg/day. These results demonstrate that the male reproductive system is far more sensitive to DEHP early in development than when animals are exposed as juveniles or adults. The effects of DEHP on male reproductive organs and sexual behaviors and the lack of significant effects on time to vaginal opening and first estrus in their littermates demonstrate that DEHP (and/or its metabolites) affects development of the male reproductive system primarily by acting as an antiandrogen. The pattern of effects of in utero and lactational DEHP exposure differed from patterns caused by other phthalate esters, and the preponderance of anterior prostate agenesis appears to be unique among all chemicals. These results suggest that DEHP acts partly by mechanisms distinct from those of other antiandrogens.

Abnormalities of sexual development in male rats with in utero and lactational exposure to the antiandrogenic plasticizer Di(2-ethylhexyl) phthalate.

Several members of the phthalate ester family have antiandrogenic properties, yet little is known about how exposure to these ubiquitous environmental contaminants early in development may affect sexual development. We conducted experiments to determine effects of in utero and lactational exposure to the most prevalent phthalate ester, di(2-ethylhexyl) phthalate (DEHP), on male reproductive system development and sexual behavior. Sprague-Dawley rats were dosed with corn oil or DEHP (0, 375, 750, or 1,500 mg/kg/day, per os) from gestation day 3 through postnatal day (PND) 21. Dose-related effects on male offspring included reduced anogenital distance, areola and nipple retention, undescended testes, and permanently incomplete preputial separation. Testis, epididymis, glans penis, ventral prostate, dorsolateral prostate, anterior prostate, and seminal vesicle weights were reduced at PND 21, 63, and/or 105-112. Additional dose-related effects included a high incidence of anterior prostate agenesis, a lower incidence of partial or complete ventral prostate agenesis, occasional dorsolateral prostate and seminal vesicle agenesis, reduced sperm counts, and testicular, epididymal, and penile malformations. Many DEHP-exposed males were sexually inactive in the presence of receptive control females, but sexual inactivity did not correlate with abnormal male reproductive organs. These results suggest that in utero and lactational DEHP exposure also inhibited sexually dimorphic central nervous system development. No major abnormalities were found in any of eight control litters, but DEHP caused severe male reproductive system toxicity in five of eight litters at 375 mg/kg/day, seven of eight litters at 750 mg/kg/day, and five of five litters at 1,500 mg/kg/day. These results demonstrate that the male reproductive system is far more sensitive to DEHP early in development than when animals are exposed as juveniles or adults. The effects of DEHP on male reproductive organs and sexual behaviors and the lack of significant effects on time to vaginal opening and first estrus in their littermates demonstrate that DEHP (and/or its metabolites) affects development of the male reproductive system primarily by acting as an antiandrogen. The pattern of effects of in utero and lactational DEHP exposure differed from patterns caused by other phthalate esters, and the preponderance of anterior prostate agenesis appears to be unique among all chemicals. These results suggest that DEHP acts partly by mechanisms distinct from those of other antiandrogens.

Contrasting associations of blood and semen lead concentrations with semen quality among lead smelter workers

While blood lead concentration has been inversely associated with indicators of reproductive health in occupationally exposed male workers, the utility of lead concentration in semen as an indicator of lead exposure to the male reproductive system has not been fully explored. Blood and semen lead concentrations from 81 lead smelter workers were examined in relation to semen quality and endocrine function parameters. Mean blood and semen lead concentrations were 22.8 μg/dl (range 5–58) and 1.9 μg/dl (range 0.1–17.6), respectively. Total sperm count and concentration decreased with increasing blood lead concentration; p for trend was 0.003 and 0.009, respectively. Semen lead concentration was inversely related to total sperm count (p = 0.05), ejaculate volume (p = 0.001), and serum testosterone (p = 0.004), but not to sperm concentration. The association between semen lead concentration and total sperm count was eliminated when volume was included in the model. Blood lead concentration was more consistently associated with indicators of sperm production than was semen lead. In contrast, semen lead concentration was negatively associated with circulating testosterone concentrations. Our findings indicate that measurement of semen lead may not be a valuable adjunct to conventional blood lead monitoring for investigations of male reproductive system toxicity. Am. J. Ind. Med. 34:464–469, 1998. © 1998 Wiley-Liss, Inc.