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Fattahi E, Parivar K, Jorsaraei S G A, moghadamnia A A. The effects of diazinon on testosterone, FSH and LH levels and testicular tissue in mice. IJRM 2009; 7 (2) :59-64
URL: http://ijrm.ir/article-1-145-en.html
URL: http://ijrm.ir/article-1-145-en.html
1- Department of Biology, Ayatollah Amoli Branch, Islamic Azad University, Amol, Iran , e.fattahi@iauamol.ac.ir
2- Department of Biology, Research and Science Tehran branch, Islamic Azad University, Tehran, Iran
3- Fatemeh Zahra Infertility and health reproductive research center, Babol University of Medical sciences, Babol, Iran
4- Department of Pharmacology, Babol University of Medical Sciences, Babol, Iran
2- Department of Biology, Research and Science Tehran branch, Islamic Azad University, Tehran, Iran
3- Fatemeh Zahra Infertility and health reproductive research center, Babol University of Medical sciences, Babol, Iran
4- Department of Pharmacology, Babol University of Medical Sciences, Babol, Iran
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Introduction
Diazinon (O, O-diethyl O - 2-isopropyl –6- methyl pyrimidinyl -4- g- 1- phosphorothioate) is insecticides widely used in agriculture and pest control in the environment, which can be highly toxic (1,2). “DZN is bioactived by cytochrome P450 enzymes through desulphuration to its corresponding Oxon derivative” (3).
These compounds exert inhibition on cholinesterase (ChE) activity by phosphorylation the catalytic site of the enzymes” (4). These are associated with male
reproductive system, including chromatin alterations in sperm nucleus. The main toxic action of organophosphates (OP) is phosphorylation of proteins. Chemical changes in sperm nuclear proteins (protamines), which pack DNA during the last steps of spermatogenesis, is part of the cause to male reproductive toxicity (5, 6). Some studies showed that malathion and diazinon cause significant decrease in: oocytes survival, “regulation of genes encoding proteins involved in transcription (BP75), translation (ribosomal protein S5), and mitochondrial function (cytochrome oxidase subunits I and III), therefore providing evidence for OP insecticides as toxicants for mammals oocytes during the early oogenesis” (7). The insecticides that used in commercial formulation could be toxic and harmful to the developing embryo and in-vitro fertilization (8). “OP agrochemicals frequently alter human health or development, typically because they have endocrine agonist or antagonist activities and alter hormone-regulation of gene expression” (9). So, many adverse effects by DZN have been described so far including alterations in blood factors (RBC, Hb and Hct), plasma levels of testosterone and blood glucose (10).
“Toxicity of OP mainly results in neurotoxicity due to its oxygen analogues (oxons), formed during the OP oxidative activation. OP alters semen quality and sperm chromatin and DNA at different stages of spermatogenesis. Oxons are more toxic than the parent compounds” (11). These compounds can influence the testes, for example decreasing the testis weight, sperm motility, grading and sperm viability, also they increase the sperm abnormal forms (12-13). Furthermore the OP overexposure through cutaneous absorption and inhalation has followed by neurological, skeletal and endocrine effects (14). Diazinon leading to the induction of lipid peroxidation, altrations the activities of antioxidant enzymes and DNA damage using in vitro (15). “Sublethal doses may lead to reduced growth and reproduction aquatic invertebrate, interference with algae-invertebrate interactions, reduced egg-production, delayed sexual maturity, adverse behavioral modifications in mammals and in fishes affect reproductive behavior and disrupt ovarian structure” (16,17). Some studies showed that exposure to environmental chemicals such as diazinon and malathion result in cancers or reduced reproductive functions in animals and human (18).
However, there is little information about toxicological effects of pesticides, including diazinon, on the structure of testis and sex hormones in the male mice. Therefore, the main objective of this study was to investigate the effects of diazinon on the reproduction organs of mice.
Materials and methods
Chemicals
Diazinon (DZN), a commercial formulation (60% active ingredient), was obtained from Shimi Keshavarz company of IRAN. The DZN was dissolved in corn oil and administered (i.p.) in sublethal dose.
Animals
For this experiment, adult male Balb/C mice (10-12 weeks old), were obtained from Pastor Institute. Mice were housed in a separate room cages, under controlled conditions of temperature (22±3°C), humidity (50± 5%) and light (12 light: 12 dark cycle), with access to the powdered diet and to deionized water.
The experiments were conducted at the Babol University of Medical Sciences. For this study, the male mice were divided into three groups. In the experimental group, DZN was injected to the mice as consecutive doses (30mg/kg i.p, five consecutive days per week for one month). Sham received only the vehicle under the same conditions (corn oil injection) and control group kept with no injection till end of experiment. Animals were sacrificed by ether, 7 days after the last DZN injection.
Histopathological examinations
After the last DZN injection and at the time of tissue collection, testes were immediately fixed in 10% formalin solution. For each testis, serial sections (5 µm thick) were made. These sections were stained by hematoxylin-eosin (H & E) and morphometrically examined by light microscopy.
Morphometrical analysis of the testis
Testes were examined for structural changes. The following parameters were recorded: weight and diameter of testis, numbers of germ cells, spermatocyts, spermatids, Leydig cells, and the seminiferous tubules diameter (STD) which was measured by light microscope equipped by eyepiece graticule.
Hormones measurements
Serum LH and FSH were measured by double antibody radioimmunoassay as previously described (19, 20). Serum testosterone was assayed using a competitive chemiluminescent immunoassay kit (DRG Co, Germany; and Pishtaz Teb, Iran).
Statistical analysis
Data were represented as means±S.E. The differences were compared for statistical significance by one way ANOVA followed by Tukey post hoc test. Differences was considered significant at p<0.05.
Results
Effects of diazinon on testes
Normal spermatogenesis could be seen in the testes sections of the control group (Figure 1). However, different degrees of degenerative changes in testes were observed in the DZN treated group (Figure 2).
Sublethal dose of DZN in experimental group (30mg/kg) markedly reduced the diameter of seminiferous tubules (p<0.001) (Table I), which showed a variety of cellular damages including decrease in the number of germ cells of the tubules (p<0.001) (Table I).
In this study, interaperitoneal (i.p.) administration of diazinon significantly reduced numbers of spermatocytes: control (38.5±1.1), DZN (35.02±0.8) and spermatids: control (12.04±0.23), DZN (9.38±0.41) (p<0.001) (Table I). Weight of testis was reduced in the mice receiving diazinon (7.32±0.32 mg), compared to the control group (8.28±0.29 mg) (p<0.05) (Table I). Testes relative weights were significantly increased by diazinon (30mg/kg,i.p.) compared to the control group. There were significant differences between the number of Leydig cells in the control and DZN groups (11.37±0.36 and 6.29±0.36 in control and DZN groups respectively) (Figure 3). The mean numbers of Sertoli cells on the control group was 2.08±0.18 while in DZN group it was significantly reduced to 1.10±0.093 (p<0.001) (Table I). Macroscopic studies showed that diazinon reduced testis diameter in the consecutive doses of DZN (6.44±0.18) compared with control group (7.01±0.48) (p<0.001) (Table I).
Effects of diazinon on sexual hormones
Diazinon significantly decreased the serum testosterone levels (3.68±0.91) in the experimental group compared with control (15.2±1.01) (p<0.001) (Table I). The levels of serum FSH was significantly higher in DZN group (5.4± 1.05) compared with the control group (2.5±0.53) (p<0.001) (Table I). The LH levels of the control group and DZN group were (3±0.53) and (4±0.64) respectively which were significantly different (p<0.001) (Table I).
Table I. The effect of IP injection of diazinon on testicular tissue and sex hormones.
_86-58/Table_1.jpg)
_86-58/Figure_1.jpg)
Figure 1. The light microscopic photograph of mouse testis in control group staining with (H & E 40×).
_86-58/Figure_2.jpg)
Figure 2. Cross section of testis from a treated mouse with diazinon (30mg/kg) shows a decrease in the number of spermatogenic cells in the somniferous tubules (H & E 40×).
_86-58/Figure_3.jpg)
Figure 3. Effect of IP injection of DZN on the Leydig cells of testis in adult male mice.
_86-58/Figure_4.jpg)
Figure 4. Effect of IP injection of DZN on testosterone levels in adult male mice.
Discussion
Some studies have showed that DZN was capable of inducing structural and functional changes (18), and some biochemical alterations in the ovaries and testes (16). Our results demonstrate that administration of sublethal dose of diazinon can adversely effects in reproductive function by decreasing the mass of testis and testosterone blood levels, but increasing the concentrations of circulating gonadotropins.
Some histopathological studies in animals have showed that diazinon treatment may inhibit spermatogenesis and make destruction of all kind of seminiferous tubules. Maintaining LH serum levels is very important for initiating and supporting spermatogenesis, hence degeneration of Sertoli cells and germinal cells may be due to high concentrations of circulating LH (21,22). OP cause microtubule disruption of epithelium (23), and finally leads to tubular atrophy (24) Also, spermatogenesis disruption might be due to increases in the serum LH concentration which is detrimental to the germinal cells (having a very important role in the first steps of spermatogenesis process) (25, 26).
The diameters of germinal cells and spermatozoa have showed a significantly reduction after DZN treatment (16). We also observed a decreased in the number of germinal cells. This might be the cause of decreases in the number of spermatocyts and spermatids, which would eventually result in a decrease of spermatozoa. Finally DZN could reduce sperm production. Toxic effects of diazinon might be mediated by stimulation of lipid peroxidation, changes in the actions of antioxidant enzymes, DNA damage, and free radicals which involved in cell death (26, 27). Similarly we observed that DZN decrease the number of all cell types in mice testis.
Several studies have showed increased frequencies of sperm aneuploidy observed in individuals occupationally exposed to DZN (28). Also several OPs have been extensively studied as genotoxic chemicals in mammalian germinal cells and spermatids (29, 30).
Prolonged IP exposure to the DZN, decreased the body weight in consensus with the earlier reports, and that effect was due to diminished food and water intake in treated mice of DZN group (31). Decrease in testis weight revealed the fact that significant gonadotoxicity could be seen after prolonged exposure to DZN. Similar effects has been observed in many other studies after treating with low doses of Diazinon (16), which may be due to decreased acetylcholinesterase level and spermatogenic cells, sertoli cells and Leydig cells losses and testicular atrophy (32-34).
DZN has also been described as genotoxic , mutagenic carcinogenic agents mutagenic agent using in vivo and in vitro models (35, 36), probably by sharing the alkylation properties of many other OP compounds (29). DZN exposure also has caused reduction in the Leydig cells (16).
Our results demonstrated that the number of Leydig cells was decreased. This could be the cause of testosterone shortage, which is needed along with the Sertoli cells to carry out spermatogenesis (16). “Testosterone is required for differentiation of sex organs and production of sperms” (37). OP may decline serum steroid hormone levels by increasing steroid catabolism and elimination or directly inhibit steroid hormone production(38). In addition OP insecticide inhibits steroidogenesis in adrenal cells (39). Therefore,maintenance of testosterone levels very critically for spermatogenesis and fertility (40). (40), reduce serum testosterone levels due to effects of diazinon to might cause reduction in spermatogenesis and fertility in animals.
“There are several possible mechanisms for the antigonadal actions of organophosphates; they may exert a direct inhibitory action on the testis; they may affect the pituitary, causing changes in gonadotrophins concentrations and thus subsequent spermatogenic impairment; or they may change the concentration of neurotransmitter” (41).
“Antiandrogens can disrupt male differentiation by several mechanisms, including antagonism of receptor binding, or by inhibition of the production, transport, or metabolism of androgens” (39). The damage may have occurred by direct toxic effects of DZN on cells or tissue, but it might also occur because of imbalanced hormones levels.
DZN may affect directly upon testis tissue or by entering into the pituitary gland which could cause changes of gonadotropins arise. In these actions of DZN, serum LH and FSH levels increased probably due to suppression of feed-back inhibition of anterior pituitary. The suppression of feed back inhibition may secondarily increase the LH and FSH secretion. The results of the present study indicate that DZN has a direct effect on pituitary, which lead to increase in circulating LH levels. Diazinon increase serum FSH levels after injection in mice. FSH has important effects on sertoli cells. Inhibin and other factors secreted by Sertoli cells cause increase of circulating FSH levels by feed back on pituitary. Increase of LH levels has toxic effects on testis tissue.
In summary, diazinon has adversely affected the reproduction organ in male mice. The present results indicate that exposure to DZN has direct effects on mice testis and the imbalance of circulating testosterone and gonadotropins may reduce fertility.
Acknowledgment
This project was supported by a grant from Islamic Azad University, Ayatollah Amoli Branch.
Diazinon (O, O-diethyl O - 2-isopropyl –6- methyl pyrimidinyl -4- g- 1- phosphorothioate) is insecticides widely used in agriculture and pest control in the environment, which can be highly toxic (1,2). “DZN is bioactived by cytochrome P450 enzymes through desulphuration to its corresponding Oxon derivative” (3).
These compounds exert inhibition on cholinesterase (ChE) activity by phosphorylation the catalytic site of the enzymes” (4). These are associated with male
reproductive system, including chromatin alterations in sperm nucleus. The main toxic action of organophosphates (OP) is phosphorylation of proteins. Chemical changes in sperm nuclear proteins (protamines), which pack DNA during the last steps of spermatogenesis, is part of the cause to male reproductive toxicity (5, 6). Some studies showed that malathion and diazinon cause significant decrease in: oocytes survival, “regulation of genes encoding proteins involved in transcription (BP75), translation (ribosomal protein S5), and mitochondrial function (cytochrome oxidase subunits I and III), therefore providing evidence for OP insecticides as toxicants for mammals oocytes during the early oogenesis” (7). The insecticides that used in commercial formulation could be toxic and harmful to the developing embryo and in-vitro fertilization (8). “OP agrochemicals frequently alter human health or development, typically because they have endocrine agonist or antagonist activities and alter hormone-regulation of gene expression” (9). So, many adverse effects by DZN have been described so far including alterations in blood factors (RBC, Hb and Hct), plasma levels of testosterone and blood glucose (10).
“Toxicity of OP mainly results in neurotoxicity due to its oxygen analogues (oxons), formed during the OP oxidative activation. OP alters semen quality and sperm chromatin and DNA at different stages of spermatogenesis. Oxons are more toxic than the parent compounds” (11). These compounds can influence the testes, for example decreasing the testis weight, sperm motility, grading and sperm viability, also they increase the sperm abnormal forms (12-13). Furthermore the OP overexposure through cutaneous absorption and inhalation has followed by neurological, skeletal and endocrine effects (14). Diazinon leading to the induction of lipid peroxidation, altrations the activities of antioxidant enzymes and DNA damage using in vitro (15). “Sublethal doses may lead to reduced growth and reproduction aquatic invertebrate, interference with algae-invertebrate interactions, reduced egg-production, delayed sexual maturity, adverse behavioral modifications in mammals and in fishes affect reproductive behavior and disrupt ovarian structure” (16,17). Some studies showed that exposure to environmental chemicals such as diazinon and malathion result in cancers or reduced reproductive functions in animals and human (18).
However, there is little information about toxicological effects of pesticides, including diazinon, on the structure of testis and sex hormones in the male mice. Therefore, the main objective of this study was to investigate the effects of diazinon on the reproduction organs of mice.
Materials and methods
Chemicals
Diazinon (DZN), a commercial formulation (60% active ingredient), was obtained from Shimi Keshavarz company of IRAN. The DZN was dissolved in corn oil and administered (i.p.) in sublethal dose.
Animals
For this experiment, adult male Balb/C mice (10-12 weeks old), were obtained from Pastor Institute. Mice were housed in a separate room cages, under controlled conditions of temperature (22±3°C), humidity (50± 5%) and light (12 light: 12 dark cycle), with access to the powdered diet and to deionized water.
The experiments were conducted at the Babol University of Medical Sciences. For this study, the male mice were divided into three groups. In the experimental group, DZN was injected to the mice as consecutive doses (30mg/kg i.p, five consecutive days per week for one month). Sham received only the vehicle under the same conditions (corn oil injection) and control group kept with no injection till end of experiment. Animals were sacrificed by ether, 7 days after the last DZN injection.
Histopathological examinations
After the last DZN injection and at the time of tissue collection, testes were immediately fixed in 10% formalin solution. For each testis, serial sections (5 µm thick) were made. These sections were stained by hematoxylin-eosin (H & E) and morphometrically examined by light microscopy.
Morphometrical analysis of the testis
Testes were examined for structural changes. The following parameters were recorded: weight and diameter of testis, numbers of germ cells, spermatocyts, spermatids, Leydig cells, and the seminiferous tubules diameter (STD) which was measured by light microscope equipped by eyepiece graticule.
Hormones measurements
Serum LH and FSH were measured by double antibody radioimmunoassay as previously described (19, 20). Serum testosterone was assayed using a competitive chemiluminescent immunoassay kit (DRG Co, Germany; and Pishtaz Teb, Iran).
Statistical analysis
Data were represented as means±S.E. The differences were compared for statistical significance by one way ANOVA followed by Tukey post hoc test. Differences was considered significant at p<0.05.
Results
Effects of diazinon on testes
Normal spermatogenesis could be seen in the testes sections of the control group (Figure 1). However, different degrees of degenerative changes in testes were observed in the DZN treated group (Figure 2).
Sublethal dose of DZN in experimental group (30mg/kg) markedly reduced the diameter of seminiferous tubules (p<0.001) (Table I), which showed a variety of cellular damages including decrease in the number of germ cells of the tubules (p<0.001) (Table I).
In this study, interaperitoneal (i.p.) administration of diazinon significantly reduced numbers of spermatocytes: control (38.5±1.1), DZN (35.02±0.8) and spermatids: control (12.04±0.23), DZN (9.38±0.41) (p<0.001) (Table I). Weight of testis was reduced in the mice receiving diazinon (7.32±0.32 mg), compared to the control group (8.28±0.29 mg) (p<0.05) (Table I). Testes relative weights were significantly increased by diazinon (30mg/kg,i.p.) compared to the control group. There were significant differences between the number of Leydig cells in the control and DZN groups (11.37±0.36 and 6.29±0.36 in control and DZN groups respectively) (Figure 3). The mean numbers of Sertoli cells on the control group was 2.08±0.18 while in DZN group it was significantly reduced to 1.10±0.093 (p<0.001) (Table I). Macroscopic studies showed that diazinon reduced testis diameter in the consecutive doses of DZN (6.44±0.18) compared with control group (7.01±0.48) (p<0.001) (Table I).
Effects of diazinon on sexual hormones
Diazinon significantly decreased the serum testosterone levels (3.68±0.91) in the experimental group compared with control (15.2±1.01) (p<0.001) (Table I). The levels of serum FSH was significantly higher in DZN group (5.4± 1.05) compared with the control group (2.5±0.53) (p<0.001) (Table I). The LH levels of the control group and DZN group were (3±0.53) and (4±0.64) respectively which were significantly different (p<0.001) (Table I).
Table I. The effect of IP injection of diazinon on testicular tissue and sex hormones.
Figure 1. The light microscopic photograph of mouse testis in control group staining with (H & E 40×).
Figure 2. Cross section of testis from a treated mouse with diazinon (30mg/kg) shows a decrease in the number of spermatogenic cells in the somniferous tubules (H & E 40×).
Figure 3. Effect of IP injection of DZN on the Leydig cells of testis in adult male mice.
Figure 4. Effect of IP injection of DZN on testosterone levels in adult male mice.
Discussion
Some studies have showed that DZN was capable of inducing structural and functional changes (18), and some biochemical alterations in the ovaries and testes (16). Our results demonstrate that administration of sublethal dose of diazinon can adversely effects in reproductive function by decreasing the mass of testis and testosterone blood levels, but increasing the concentrations of circulating gonadotropins.
Some histopathological studies in animals have showed that diazinon treatment may inhibit spermatogenesis and make destruction of all kind of seminiferous tubules. Maintaining LH serum levels is very important for initiating and supporting spermatogenesis, hence degeneration of Sertoli cells and germinal cells may be due to high concentrations of circulating LH (21,22). OP cause microtubule disruption of epithelium (23), and finally leads to tubular atrophy (24) Also, spermatogenesis disruption might be due to increases in the serum LH concentration which is detrimental to the germinal cells (having a very important role in the first steps of spermatogenesis process) (25, 26).
The diameters of germinal cells and spermatozoa have showed a significantly reduction after DZN treatment (16). We also observed a decreased in the number of germinal cells. This might be the cause of decreases in the number of spermatocyts and spermatids, which would eventually result in a decrease of spermatozoa. Finally DZN could reduce sperm production. Toxic effects of diazinon might be mediated by stimulation of lipid peroxidation, changes in the actions of antioxidant enzymes, DNA damage, and free radicals which involved in cell death (26, 27). Similarly we observed that DZN decrease the number of all cell types in mice testis.
Several studies have showed increased frequencies of sperm aneuploidy observed in individuals occupationally exposed to DZN (28). Also several OPs have been extensively studied as genotoxic chemicals in mammalian germinal cells and spermatids (29, 30).
Prolonged IP exposure to the DZN, decreased the body weight in consensus with the earlier reports, and that effect was due to diminished food and water intake in treated mice of DZN group (31). Decrease in testis weight revealed the fact that significant gonadotoxicity could be seen after prolonged exposure to DZN. Similar effects has been observed in many other studies after treating with low doses of Diazinon (16), which may be due to decreased acetylcholinesterase level and spermatogenic cells, sertoli cells and Leydig cells losses and testicular atrophy (32-34).
DZN has also been described as genotoxic , mutagenic carcinogenic agents mutagenic agent using in vivo and in vitro models (35, 36), probably by sharing the alkylation properties of many other OP compounds (29). DZN exposure also has caused reduction in the Leydig cells (16).
Our results demonstrated that the number of Leydig cells was decreased. This could be the cause of testosterone shortage, which is needed along with the Sertoli cells to carry out spermatogenesis (16). “Testosterone is required for differentiation of sex organs and production of sperms” (37). OP may decline serum steroid hormone levels by increasing steroid catabolism and elimination or directly inhibit steroid hormone production(38). In addition OP insecticide inhibits steroidogenesis in adrenal cells (39). Therefore,maintenance of testosterone levels very critically for spermatogenesis and fertility (40). (40), reduce serum testosterone levels due to effects of diazinon to might cause reduction in spermatogenesis and fertility in animals.
“There are several possible mechanisms for the antigonadal actions of organophosphates; they may exert a direct inhibitory action on the testis; they may affect the pituitary, causing changes in gonadotrophins concentrations and thus subsequent spermatogenic impairment; or they may change the concentration of neurotransmitter” (41).
“Antiandrogens can disrupt male differentiation by several mechanisms, including antagonism of receptor binding, or by inhibition of the production, transport, or metabolism of androgens” (39). The damage may have occurred by direct toxic effects of DZN on cells or tissue, but it might also occur because of imbalanced hormones levels.
DZN may affect directly upon testis tissue or by entering into the pituitary gland which could cause changes of gonadotropins arise. In these actions of DZN, serum LH and FSH levels increased probably due to suppression of feed-back inhibition of anterior pituitary. The suppression of feed back inhibition may secondarily increase the LH and FSH secretion. The results of the present study indicate that DZN has a direct effect on pituitary, which lead to increase in circulating LH levels. Diazinon increase serum FSH levels after injection in mice. FSH has important effects on sertoli cells. Inhibin and other factors secreted by Sertoli cells cause increase of circulating FSH levels by feed back on pituitary. Increase of LH levels has toxic effects on testis tissue.
In summary, diazinon has adversely affected the reproduction organ in male mice. The present results indicate that exposure to DZN has direct effects on mice testis and the imbalance of circulating testosterone and gonadotropins may reduce fertility.
Acknowledgment
This project was supported by a grant from Islamic Azad University, Ayatollah Amoli Branch.
Type of Study: Original Article |
References
1. Sarabia L, Maurer I, Bustos-Obregón E. Melatonin prevents damage elicited by the organophosphorous pesticide diazinon on the mouse testis. Ecotoxicol Environ Saf 2009; 72: 938-942 [DOI:10.1016/j.ecoenv.2008.04.022]
2. Poet TS, Kousba AA, Dennison SL, Timchalk C. Physiologically base pharmacokinetic/pharmacodynamic model for the organophosphorus pesticide diazinon. Neurotoxicology 2004; 25:1013-1030. [DOI:10.1016/j.neuro.2004.03.002]
3. Sams C, Cocker J, Lennard MS. Biotransformation of chlorpyrifos and diazinon by human liver microsomes and recombinant human cytochrome P450s (CYP). Xenobiotica 2004; 34:861-873. [DOI:10.1080/00498250400017273]
4. Slotkin TA, Seidler FJ. Comparative developmental neurotoxicity of organophosphates in vivo: Transcriptional responses of pathways for brain cell development, cell signaling, cytotoxicity and neurotransmitter systems. Brain Res Bull 2007; 30: 232-274. [DOI:10.1016/j.brainresbull.2007.01.005]
5. Bustos-Obregon E, Gonzalez JR, Espinoza O. Melatonin as protective agent for the cytotoxic effects of diazinon in the spermatogenesis in the earthworm Eisenia foetida. Ital J Anat Embryol 2005; 110:159-165.
6. Pina-Guzman B, Solis-Heredia MJ, Quintanilla-Vega B. Diazinon alters sperm chromatin structure in mice by phosphorylating nuclear protamines. Toxicol Appl Pharmacol 2005; 15: 189-198. [DOI:10.1016/j.taap.2004.06.028]
7. Bonilla E, Hernández F, Cortés L, Mendoza M, Mejía J, Carrillo E, et al. Effects of the insecticides malathion and diazinon on the early oogenesis in mice in vitro. Environ Toxicol 2008; 23: 240-245. [DOI:10.1002/tox.20332]
8. Ducolomb Y, Casas E, Valdez A, González G, Altamirano-Lozano M, Betancourt M. In vitro effect of malathion and diazinon on oocytes fertilization and embryo development in porcine. Cell Biol Toxicol 2009 17. [DOI:10.1007/s10565-008-9117-3]
9. Mankame T, Hokanson R, Fudge R, Chowdhary R, Busbee D. Alteration of gene expression in human cells treated with the agricultural chemical diazinon: possible interaction in fetal development. Hum Exp Toxicol 2006; 25: 225-233. [DOI:10.1191/0960327106ht622oa]
10. Alahyary P, Poor MI, Azarbaijani FF, Nejati V. The potential toxicity of diazinon on physiological factors in male rat. Pak J Biol Sci 2008; 11:127-130. [DOI:10.3923/pjbs.2008.127.130]
11. Salazar-Arredondo E, de Jesús Solís-Heredia M, Rojas-García E, Hernández-Ochoa I, Quintanilla-Vega B. Sperm chromatin alteration and DNA damage by methyl-parathion, chlorpyrifos and diazinon and their oxon metabolites in human spermatozoa. Reprod Toxicol 2008; 25: 455-460. [DOI:10.1016/j.reprotox.2008.05.055]
12. Kolstad HA, Bonde JP, Spano M, Giwercman A, Zschiesche W, Kaae D, et al. Change in semen quality and sperm chromatin structure following occupational styrene exposure. Int Arch Occup Environ Health 1999; 7, 135-141. [DOI:10.1007/s004200050352]
13. Swan SH, Kruse RL, Liu F, Barr DB, Drobnis EZ, Redmon JB, et al. Study for Future Families Research Group. Semen quality in relation to biomarkers of pesticide exposure. Environ Health Perspect 2003; 111:1478-1484. [DOI:10.1289/ehp.6417]
14. Dahlgren JG, Takhar HS, Ruffalo CA, Zwass M. Health effects of diazinon on a family. J Toxicol Clin Toxicol 2004; 42: 579-591. [DOI:10.1081/CLT-200026979]
15. Altuntas I, Kilinc I, Orhan H, Demirel R, Koylu H, Delibas N. The effects of diazinon on lipid peroxidation and antioxidant enzymes in erythrocytes in vitro. Hum Exp Toxicol 2004; 23: 9-13. [DOI:10.1191/0960327104ht408oa]
16. Dutta HM, Meijer HJ. Sublethal effects of diazinon on the structure of the testis of bluegill, Lepomis macrochirus: a microscopic analysis. Enviromental pollution 2003; 125: 355-360. [DOI:10.1016/S0269-7491(03)00123-4]
17. Maxwell LB, Dutta HM. Diazinon-induced endocrine disruption in bluegill sunfish, Lepomis macrochirus. Ecotoxicol Environ Saf 2005; 60: 21-27. [DOI:10.1016/j.ecoenv.2003.12.015]
18. Wesseling C, Antich D, Hogstedt C, Rodríguez AC, Ahlbom A. Geographical differences of cancer incidence in Costa Rica in relation to environmental and occupational pesticide exposure. Int J Epidemiol 1999; 28: 365-374. [DOI:10.1093/ije/28.3.365]
19. Pidoux G, Gerbaud P, Tsatsaris V, Marpeau O, Ferreira F, Meduri G, et al. Biochemical characterization and modulation of LH/CG-receptor during human trophoblast differentiation. J Cell Physiol 2007; 212: 26-35. [DOI:10.1002/jcp.20995]
20. Peegel H, Towns R, Nair A, Menon KM. A novel mechanism for the modulation of luteinizing hormone receptor mRNA expression in the rat ovary. Mol Cell Endocrinol 2005; 233: 65-72. [DOI:10.1016/j.mce.2004.12.009]
21. Shan L, Hardy DO, Catterall JF, Hardy MP. Effects of luteinizing hormone (LH) and androgen on steady state levels of messenger ribonucleic acid for LH receptors, androgen receptors, and steroidogenic enzymes in rat Leydig cell progenitors in vivo. Endocrinology 1995; 136: 1686-1693. [DOI:10.1210/endo.136.4.7895679]
22. Sarkar R, Mohanakumar KP, Chowdhury M. Effects of an organophosphate pesticide, quinalphos, on the hypothalamo-pituitary-gonadal axis in adult male rats. Journal of Reproduction and Fertility 2000; 118: 29-38 [DOI:10.1530/jrf.0.1180029]
23. Nakai M, Hess RA, Netsu J, Nasu T. Deformation of the rat Sertoli cell by oral administration of carbendazim (methyl 2-benzimidazole carbamate). J Androl 1995; 16: 410-416.
24. Hess RA, Nakai M. Histopathology of the male reproductive system induced by the fungicide benomyl. Histol Histopathol 2000; 15: 207-224.
25. Boekelheide K, Schoenfeld HA. Spermatogenesis by Sisyphus: proliferating stem germ cells fail to repopulate the testis after 'irreversible' injury. Adv Exp Med Biol 2001; 500: 421-428. [DOI:10.1007/978-1-4615-0667-6_64]
26. Izumi H, Kimura E, Ota T, Shimazu S. A two-generation reproductive toxicity study of n-butylbenzene in rats. J Toxicol Sci 2005; 30: 21-38. [DOI:10.2131/jts.30.S21]
27. Ibrahim NA, El-Gamal BA. Effect of diazinon, an organophosphate insecticide, on plasma lipid constituents in experimental animals. J Biochem Mol Biol 2003; 36: 499-504. [DOI:10.5483/BMBRep.2003.36.5.499]
28. Narayana K, Prashanthi N, Nayanatara A, Bairy LK, D'Souza UJ. An organophosphate insecticide methyl parathion (o- o- dimethyl o - 4 - nitrophenyl phosphorothioate) induces cytotoxic damage and tubular atrophy in the testis despite elevated testosterone level in the rat. J Toxicol Sci 2006; 31:177-189. [DOI:10.2131/jts.31.177]
29. Recio R, Robins WA, Ocmpo-Gomez G, Borja-AburtoV. Organophosphorus pesticide exposure increase the frequeny of sperm sex null aneuploidy. Environ Health Prspect 2001; 109:1237-1240. [DOI:10.1289/ehp.011091237]
30. Cakir S, Sarikaya R. Genotoxicity testing of some organophosphate insecticides in the Drosophila wing spot test. Food Chem Toxicol 2005; 43: 443-450. [DOI:10.1016/j.fct.2004.11.010]
31. Prashanthi N, Narayana K, Nayanatara A, Chandra Kumar HH, Bairy KL, D'Souza UJ. The reproductive toxicity of the organophosphate pesticide 0, 0-dimethyl 0-4-nitrophenyl phosphorothioate (methyl parathion) in the male rat. Folia Morphol (Warsz) 2006; 65: 309-321.
32. Maitra SK, Sarkar R. Influence of methyl parathion on gametogenic and acetylcholinesterase activity in the testis of whitethroated munia (Lonchura malabarica). Arch Environ Contam Toxicol 1996; 30: 384-389 [DOI:10.1007/BF00212298]
33. Salem KA. Infectious diseases among food handlers. J Egypt Public Health Assoc 1998; 73: 563-575.
34. Hatjian BA, Mutch E, Williams FM, Blain PG, Edwards JW. Cytogenetic response without changes in peripheral cholinesterase enzymes following exposure to a sheep dip containing diazinon in vivo and in vitro. Mutat Res 2000; 427, 85-92. [DOI:10.1016/S1383-5718(00)00131-5]
35. Aluigi MG, Angelini C, Falugi C, Fossa R, Genever P, Gallus L, et al. Interaction between organophosphate compounds and cholinergic functions during development. Chem Biol Interact 2005; 157-158:305-316. [DOI:10.1016/j.cbi.2005.10.037]
36. LeBlanc G, Bain LG, Wilson VS. Pesticides:Multiple mechanisms of demasculi- nization. Mol Cell Endocrinol 1997; 126:1-5. [DOI:10.1016/S0303-7207(96)03968-8]
37. Watanabe HK, Hoskins B, Ho IK. Selective inhibitory effect of organophosphates on UDP-glucuronyl transferase activities in rat liver microsomes. Biochem Pharmacol 1986; 35:455-460. [DOI:10.1016/0006-2952(86)90219-4]
38. Civen M, Brown CB. The effect of organophosphate insecticides on adrenal corticosterone formation. Pesticide Biochemistry and Physiology 1974; 4: 254-259. [DOI:10.1016/0048-3575(74)90108-4]
39. Chattopadhyay A, Sarkar M, Biswas NM. Dose-dependent effect of copper chloride on male reproductive function in immature rats. Kathmandu Univ Med J (KUMJ) 2005; 3: 392-400.
40. Pidoux G, Gerbaud P, Tsatsaris V, Marpeau O, Ferreira F, Meduri G, et al. Biochemical characterization and modulation of LH/CG-receptor during human trophoblast differentiation. J Cell Physiol 2007; 212: 26-35. [DOI:10.1002/jcp.20995]
41. Tamura H, Maness SC, Reischmann K, Dorman DC, Gray LE, Gaido KW. Androgen receptor antagonism by the organophosphate insecticide fenitrothion. Toxicol Sci 2001; 60: 56-62. [DOI:10.1093/toxsci/60.1.56]
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