MyMedR

Effect of tamoxifen on spermatogenesis and tubular morphology in rats

D'Souza UJ

Asian J Androl, 2004 Sep;6(3):223-6.

PMID: 15273871

To observe the effect of tamoxifen citrate on spermatogenesis and tubular morphology in rats.

Tamoxifen induced multinucleated cells (symplasts) and distortion of seminiferous tubules in rat testis

D'Souza UJ

Asian J Androl, 2003 Sep;5(3):217-20.

PMID: 12937805

To evaluate the effect of tamoxifen citrate on male reproductive system of rat.

Pre- and postnatal toxicity of diazinon induces disruption of spermatogenetic cell line evidenced by increased testicular marker enzymes activities in rat offspring

Jayachandra S, D'Souza UJ

J Environ Pathol Toxicol Oncol, 2013;32(1):73-90.

PMID: 23758154

The objective of this study was to study the possible reproductive adverse effects of the diazinon on rat offspring exposed in utero and during lactation. Dams were gavaged daily (10, 15, and 30 mg/kg) before mating, during mating, and during pregnancy and lactation in separate groups. Reproductive outcome data of dams were examined. Body weight, testis weight, testicular marker enzyme activities (alkaline phosphatase, acid phosphatase, lactate dehydrogenase, and glucose-6-phosphate dehydrogenase), qualitative and quantitative testicular and epididymal histology, and immunohistochemisty for 3-β-hydroxysteroid dehydrogenase (HSD) were examined in male offspring at puberty and adulthood. The 30-mg/kg dose induced significant adverse effects at both puberty and adulthood in offspring. At puberty the male offspring showed a decrease in testicular weight, degenerative changes, and 3-β-HSD. Moreover, an increase in activity of alkaline and acid phosphatase also was observed. At adulthood, there was a decrease in testicular weight and 3-β-HSD with an increase in the levels of testicular marker enzyme. There was evidence of some adverse reproductive effects in male offspring at the 15-mg/kg dose. Most of the adverse effects were irreversible and were evident at both puberty and adulthood in offspring, although a few parameters reverted back to the normal growth pattern. Hence, diazinon is a reproductive toxicant in male offspring, which caused significant damage to the testes when exposed during prenatal and postnatal life.

Fulltext Toxic effects of 5-Fluorouracil on sperm count in wistar rats

D'Souza UJ

Malays J Med Sci, 2003 Jan;10(1):43-5.

PMID: 23365499 MyJurnal

The antimetabolite, 5-fluorouracil is widely used in the treatment of cancers. Although its toxic effects on testis causing germinal epithelial sloughing, tubular atrophy and generation of multinucleated cells were reported, its effect on spermatogenesis has not been studied. Hence the present study was conducted to evaluate the effects of 5-fluorouracil on epididymal sperm count. Male Wistar rats were employed in the study (n=5 per group). The animals were injected (i.p) with five consecutive doses of 5-fluorouracil (10, 20, 30mg/kg b.w) at an interval of 24h and the control with 0.1ml-distilled water. Samples were obtained at 14, 35, 42 and 70 days after injection. Rats were sacrificed, a laparatomy was performed and epididymes were collected in 1ml phosphate buffered saline (pH 7.2), minced, filtered and stained with 1% aqueous eosin Y. An aliquot was taken in leucocyte pipette, diluted with phosphate buffered saline and sperm count was done as per the standard procedure. Data were analyzed by Mann Whitney U test. The results of this study revealed that 5 - fluorouracil significantly decreased the sperm count in a dose- and time-dependent manner.

Prenatal and postnatal exposure to diazinon and its effect on spermatogram and pituitary gonadal hormones in male offspring of rats at puberty and adulthood

Jayachandra S, D'Souza UJ

J Environ Sci Health B, 2014;49(4):271-8.

PMID: 24502214 DOI: 10.1080/03601234.2014.868287

The objective of this research is to study the possible reproductive adverse effects of diazinon on rat offspring exposed in utero and during lactation. Twenty-four Sprague-Dawley female rats (10-12 week old) were randomly assigned to four groups, each consisting of six rats. Group 1 served as the control and these rats were given normal saline orally. Rats in groups 2, 3, and 4 were administered diazinon, dissolved in saline at 10, 15, 30 mg/ kg(-1) body weight, per oral, once daily, during mating, pregnancy and lactation. The male offsprings were examined at puberty and adulthood for body weight, testis weight, epididymis weight, sperm count, motility and morphology, pituitary-gonadal hormone levels. At 30 mg kg(-1) dose, the male offsprings showed a decrease in testicular weight, sperm count, motility, with an increase in abnormal sperm percentage and a decline in pituitary-gonadal hormones, at puberty. Upon attaining adulthood, there was a decrease in testicular weight, sperm count and motility with an increase in abnormal sperm percentage and a decrease in pituitary hormone level. There was evidence of some adverse reproductive effects on the male offspring at the 15 mg/ kg(-1) dose. Most of the adverse effects were irreversible and were evident at both puberty and adulthood in the offsprings, although a few parameters reverted to the normal growth pattern. Diazinon is a reproductive toxicant for male offsprings if exposed during prenatal and postnatal phases.

Genotoxic and cytotoxic effects in the bone marrow of rats exposed to a low dose of paraquat via the dermal route

D'Souza UJ, Zain A, Raju S

Mutat Res, 2005 Mar 7;581(1-2):187-90.

PMID: 15725618

The genotoxic effect of the herbicide paraquat was studied in rat bone-marrow by means of the micronucleus assay. Paraquat at dose levels of 6, 15 and 30 mg/kg body weight was given to rats in a single application via the dermal route. Marrow was collected at 24, 48 and 72 h after the application. The micronucleus assay was done as recommended by standard procedures. Paraquat gave rise to an increase in the number of micronuclei in a dose-dependent manner. The number of micronucleated polychromatic erythrocytes showed a maximum at 48 h and the toxicity was further prolonged, as there was no complete recovery at 72 h. These findings suggest a genotoxic effect of paraquat even after exposure via dermal application.

Effects of pesticide use on semen quality among farmers in rural areas of Sabah, Malaysia

Hossain F, Ali O, D'Souza UJ, Naing DK

J Occup Health, 2010;52(6):353-60.

PMID: 20924153

OBJECTIVES: To determine the relationship between semen quality and exposure to pesticide residues.

METHODS: A cross-sectional study was conducted among male farmers from 3 different communities in Sabah, Malaysia. A total of 152 farmers participated in this study of whom 62 farmers had been exposed to either paraquat or malathion or both to varying extents. Questionnaires were designed to record a history of pesticides exposure and other potential risk factors among farmers. All semen samples were collected, processed and analyzed by qualified personnel based on WHO guidelines. Volume, pH, sperm concentration, motility, morphology and WBC count were examined and recorded. The association between pesticide exposure and semen parameters was highly significant.

RESULTS: The mean values of volume, pH, sperm concentration, motility, and WBC count were significantly less in the exposed group than in compared with the non-exposed group, with p<0.005. Those who were exposed to pesticides had greater risk of having abnormal semen parameters than those in with the non exposed group, with p values of less than 0.05. The comparison between semen qualities such as lower sperm count, motility and higher percentage of sperm abnormality of those exposed to different types of pesticides (paraquat and malathion) showed no significant differences.

CONCLUSION: The results showed a significant decline in semen quality with a decline in sperm count, motility and higher percent of teratospermia among subjects with pesticide exposure, and those who were exposed to pesticides had significantly 3 to 9 times greater risk of having abnormal semen parameters.

Dermal exposure to the herbicide-paraquat results in genotoxic and cytotoxic damage to germ cells in the male rat

D'Souza UJ, Narayana K, Zain A, Raju S, Nizam HM, Noriah O

Folia Morphol (Warsz), 2006 Feb;65(1):6-10.

PMID: 16783728

The effects of exposure to low doses of paraquat, a herbicide, via the dermal route were studied on the spermatozoa of Sprague-Dawley rats. Paraquat (1, 1'-dimethyl-4, 4'-bipyridinium dichloride) was administered once a day for five days, at intervals of 24 h at 0, 6, 15 and 30 mg/kg, and the rats were sacrificed on days 7, 14, 28, and 42 after the last exposure. The sperm suspensions were obtained by mincing the caudae epididymes and ductus deferens for the purpose of performing a sperm morphology test, sperm count and analysis of sperm mortality and sperm motility, as per the standard procedures. The sperm count was decreased (p < 0.05) only on days 7 and 14 but sperm abnormalities increased on all days (p < 0.05). Sperm mortality increased at higher dose-levels (p < 0.05) except on day 42, and motility was affected by 30 mg/kg only on day 42. In conclusion, paraquat is a genotoxic and cytotoxic agent to germ cells in the male rat.

Fulltext Lipid peroxidation and decline in antioxidant status as one of the toxicity measures of diazinon in the testis

Leong CT, D'Souza UJ, Iqbal M, Mustapha ZA

Redox Rep, 2013;18(4):155-64.

PMID: 23849340 DOI: 10.1179/1351000213Y.0000000054

The rapid emergence of various pesticides in the market is inevitable due to the demands from agriculture industries and domestic needs to control nuisance pests and to sustain green resources worldwide. However, long-term exposure to pesticide has led to adverse effects on male fertility. Organophosphate diazinon (O,O-diethyl-O-[2-isopropyl-6-methyl-4-pyrimidinyl] phosphorothiote) is an often abusively used pesticide, as it is effective and economical. This study is to determine the adverse effects of low-dose diazinon exposure on the male reproductive system. In this study, 72 Sprague-Dawley rats were segregated into 1, 2, and 8 weeks of exposure groups and further sub-grouped (n = 6) to receive 0, 10, 15, and 30 mg/kg body weight diazinon treatment. Rats were gavaged orally with diazinon and sacrificed under anaesthesia the day after the last exposure. Our results showed that consistent diazinon exposure decreased glutathione and catalase, and increased lipid peroxidation which together lead to diazinon-mediated oxidative stress. Additionally, diazinon increased serum lactate dehydrogenase and decreased serum testosterone, which may have caused sperm and histopathological anomalies. In conclusion, exposure to diazinon caused changes in lipid peroxidation and sperm, and these two effects might be causally linked.

Exogenous leptin administration decreases sperm count and increases the fraction of abnormal sperm in adult rats

Haron MN, D'Souza UJ, Jaafar H, Zakaria R, Singh HJ

Fertil Steril, 2010 Jan;93(1):322-4.

PMID: 19709655 DOI: 10.1016/j.fertnstert.2009.07.995

Daily intraperitoneal injection of 5-30 microg/kg body weight of leptin for 42 days to adult rats decreases sperm count and increases the fraction of abnormal sperm.

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